The Experts below are selected from a list of 429 Experts worldwide ranked by ideXlab platform
Sean P Mahabir - One of the best experts on this subject based on the ideXlab platform.
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efficacy of a novel oral Chewable Tablet containing sarolaner moxidectin and pyrantel simparica trio against natural flea and tick infestations on dogs presented as veterinary patients in europe
Parasites & Vectors, 2020Co-Authors: Csilla Becskei, Sean P Mahabir, Daphne Fias, Róbert FarkasAbstract:A novel Chewable oral Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) has recently been developed to provide persistent protection against flea and tick infections for a month, treatment of hookworm and roundworm infections and prevention of heartworm and lungworm disease in dogs. Two field studies were conducted to evaluate the safety and efficacy of Simparica Trio™ against natural flea and tick infestations on dogs in Europe. Dogs with natural flea or tick infestations were allocated randomly to treatment on Day 0 with either Simparica Trio™ Tablets (flea study: n = 297; tick study: n = 189) to provide 1.2–2.4 mg/kg sarolaner, 24–48 µg/kg moxidectin and 5–10 mg/kg pyrantel (as pamoate salt) or with NexGard® Spectra (afoxolaner + milbemycin oxime) according to the label instructions (flea study: n = 164; tick study: n = 91). Efficacy was calculated based on the mean percent reduction in live parasite counts compared to the respective pre-treatment counts on Days 14 and 30 in the flea study and on Days 7, 14, 21 and 30 in the tick study. To count the fleas, the dog’s entire coat was systematically combed using an extra fine-tooth flea comb until all fleas were removed. For the tick counts, the dog’s entire coat was searched manually. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea allergic dogs in the flea study. Palatability was assessed in both studies. Simparica Trio™ was well tolerated in both studies. Efficacy against fleas was ≥ 97.9% in the Simparica Trio™ group and ≥ 96.1% in the NexGard® Spectra group. Efficacy against ticks was ≥ 94.8% in the Simparica Trio™ group and ≥ 94.4% in the NexGard® Spectra group. Clinical signs of flea allergy dermatitis improved following treatment with Simparica Trio™. Simparica Trio™ Tablets were voluntarily and fully consumed on ≥ 78% of the 485 occasions they were offered. A single oral dose of Simparica Trio™ was safe and highly efficacious against naturally occurring flea and tick infestations for 1 month on dogs. Clinical signs of FAD improved following treatment. Simparica Trio™ was voluntarily and readily consumed by most dogs.
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efficacy of a new oral Chewable Tablet containing sarolaner moxidectin and pyrantel simparica trio against induced ascarid infections in dogs
Parasites & Vectors, 2020Co-Authors: Csilla Becskei, Susan J Holzmer, Kristina Kryda, Mirjan Thys, Laurel Bowersock, Tiago Fernandes, Leon Meyer, Craig R Reinemeyer, Sean P MahabirAbstract:Ascarid infections are among the most prevalent intestinal parasitic infections occurring in dogs around the world, with Toxocara canis and Toxascaris leonina commonly observed. Toxocara canis can cause considerable disease in dogs and humans, and year-round prophylactic treatment and control in dogs is recommended. Elimination of immature stages of these parasites before egg-laying will reduce environmental contamination and the risk of infection for both dogs and humans. Studies were conducted to evaluate the efficacy of a novel, oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced immature adult (L5) and adult T. canis, and adult T. leonina infections in dogs. Six negative-controlled, masked, randomized laboratory studies were conducted. Two studies each evaluated efficacy against immature adult (L5) T. canis, adult T. canis, and adult T. leonina. Sixteen to 40 dogs were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo Tablets or Simparica Trio™ Tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy was based on the number of worms recovered at necropsy 7–10 days after treatment compared to placebo control. Based on geometric mean worm counts, efficacy of the sarolaner + moxidectin + pyrantel combination was ≥ 95.2% against immature adult T. canis, ≥ 97.3% against adult T. canis, and ≥ 89.7% against adult T. leonina. There were no treatment-related adverse events in any study. These studies confirm the efficacy of a single dose of a new oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against immature adult and adult T. canis, and adult T. leonina infections in dogs.
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Efficacy of a new oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced ascarid infections in dogs
Parasites & Vectors, 2020Co-Authors: Csilla Becskei, Susan J Holzmer, Kristina Kryda, Mirjan Thys, Laurel Bowersock, Tiago Fernandes, Leon Meyer, Craig R Reinemeyer, Sean P MahabirAbstract:Background Ascarid infections are among the most prevalent intestinal parasitic infections occurring in dogs around the world, with Toxocara canis and Toxascaris leonina commonly observed. Toxocara canis can cause considerable disease in dogs and humans, and year-round prophylactic treatment and control in dogs is recommended. Elimination of immature stages of these parasites before egg-laying will reduce environmental contamination and the risk of infection for both dogs and humans. Studies were conducted to evaluate the efficacy of a novel, oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced immature adult (L_5) and adult T. canis , and adult T. leonina infections in dogs. Methods Six negative-controlled, masked, randomized laboratory studies were conducted. Two studies each evaluated efficacy against immature adult (L_5) T. canis , adult T. canis , and adult T. leonina. Sixteen to 40 dogs were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo Tablets or Simparica Trio™ Tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy was based on the number of worms recovered at necropsy 7–10 days after treatment compared to placebo control. Results Based on geometric mean worm counts, efficacy of the sarolaner + moxidectin + pyrantel combination was ≥ 95.2% against immature adult T. canis , ≥ 97.3% against adult T. canis , and ≥ 89.7% against adult T. leonina . There were no treatment-related adverse events in any study. Conclusions These studies confirm the efficacy of a single dose of a new oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against immature adult and adult T. canis , and adult T. leonina infections in dogs.
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efficacy of simparica trio a novel Chewable Tablet containing sarolaner moxidectin and pyrantel against induced hookworm infections in dogs
Parasites & Vectors, 2020Co-Authors: Csilla Becskei, Kristina Kryda, Mirjan Thys, Tiago Fernandes, Leon Meyer, Susanna Martorell, Thomas Geurden, Leentje Dreesen, Sean P MahabirAbstract:Ancylostomatids (‘hookworms’) are among the most important zoonotic nematode parasites infecting dogs worldwide. Ancylostoma caninum and Uncinaria stenocephala are two of the most common hookworm species that infect dogs. Both immature and adult stages of hookworms are voracious blood feeders and can cause death in young dogs before infection can be detected by routine fecal examination. Hence, treatment of both immature and adult stages of hookworms will decrease the risk of important clinical disease in the dog as well as the environmental contamination caused by egg-laying adults, which should reduce the risk of infection for both dogs and humans. The studies presented here were conducted to evaluate the efficacy of a novel, oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), against induced larval (L4), immature adult (L5) and adult A. caninum, and adult U. stenocephala infections in dogs. Eight negative-controlled, masked, randomized laboratory studies were conducted. Two separate studies were conducted against each of the target parasites and stages. Sixteen or 18 purpose bred dogs, 8 or 9 in each of the two treatment groups, were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo Tablets or Simparica Trio™ Tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Timing of dosing relative to parasite inoculation allowed for efficacy to be evaluated primarily against the target parasite stage. Worm counts were conducted 7 or 8 days after treatments during necropsy. Efficacy was based on the number of worms recovered at necropsy compared to placebo control. Based on geometric mean worm counts, efficacy of Simparica Trio™ was ≥ 98.4% against L4 larval stage of A. caninum, ≥ 99.8% against immature adult (L5) A. caninum, and 100% against adult A. caninum and adult U. stenocephala. These studies confirm the efficacy of a single oral dose of a novel, Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against L4 larval and immature adult (L5) A. caninum, and adult A. caninum and U. stenocephala infections in dogs.
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efficacy of a novel Chewable Tablet containing sarolaner moxidectin and pyrantel simparica trio against four common tick species infesting dogs in europe
Parasites & Vectors, 2020Co-Authors: Csilla Becskei, Julian Liebenberg, Mirjan Thys, Sean P MahabirAbstract:Tick infestations can cause direct deleterious effects to dogs as a result of tick blood-feeding, and indirectly ticks can transmit disease agents that can be detrimental to the health of both dogs and humans. Six laboratory studies were conducted to support dosage selection and efficacy confirmation of a novel combination of sarolaner, moxidectin and pyrantel against four tick species that commonly infest dogs in Europe. Two studies were conducted against Dermacentor reticulatus (one of which was a dose determination study), two against Ixodes ricinus, and one each against Ixodes hexagonus and Rhipicephalus sanguineus (sensu lato). In each study, eight purpose-bred Beagle or mix-breed dogs were randomly allocated to each treatment group and infested with 50 unfed adult ticks on Days-2, 5, 12, 19, 26 and 33. On Day 0 dogs were treated orally with placebo or the combination product. In the dose determination study, dogs received sarolaner at point dosages of 0.6 mg/kg, 1.2 mg/kg or 2.4 mg/kg in combination with moxidectin and pyrantel, and in all other studies dogs received Simparica Trio™ to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt). Efficacy was assessed based on live tick counts conducted 48 hours after treatment and each weekly infestation. There were no treatment-related adverse events in any study. In the dose determination study, 1.2 mg/kg sarolaner was the lowest dosage evaluated that provided > 90% efficacy for at least 28 days and therefore was selected as the dosage to provide tick control for at least one month following a single oral treatment. In the dose confirmation studies, a single oral dose of Simparica Trio™ provided ≥ 99.2% efficacy against existing infestations of all tick species, and against re-infestations efficacy was ≥ 97.2% against D. reticulatus for 28 days and against all other species for 35 days. These studies support the sarolaner dose selected and confirm the efficacy of a single oral dose of Simparica Trio™ against existing infestations and re-infestations of the common tick species infesting dogs in Europe for at least one month.
Csilla Becskei - One of the best experts on this subject based on the ideXlab platform.
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efficacy of a novel oral Chewable Tablet containing sarolaner moxidectin and pyrantel simparica trio against natural flea and tick infestations on dogs presented as veterinary patients in europe
Parasites & Vectors, 2020Co-Authors: Csilla Becskei, Sean P Mahabir, Daphne Fias, Róbert FarkasAbstract:A novel Chewable oral Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) has recently been developed to provide persistent protection against flea and tick infections for a month, treatment of hookworm and roundworm infections and prevention of heartworm and lungworm disease in dogs. Two field studies were conducted to evaluate the safety and efficacy of Simparica Trio™ against natural flea and tick infestations on dogs in Europe. Dogs with natural flea or tick infestations were allocated randomly to treatment on Day 0 with either Simparica Trio™ Tablets (flea study: n = 297; tick study: n = 189) to provide 1.2–2.4 mg/kg sarolaner, 24–48 µg/kg moxidectin and 5–10 mg/kg pyrantel (as pamoate salt) or with NexGard® Spectra (afoxolaner + milbemycin oxime) according to the label instructions (flea study: n = 164; tick study: n = 91). Efficacy was calculated based on the mean percent reduction in live parasite counts compared to the respective pre-treatment counts on Days 14 and 30 in the flea study and on Days 7, 14, 21 and 30 in the tick study. To count the fleas, the dog’s entire coat was systematically combed using an extra fine-tooth flea comb until all fleas were removed. For the tick counts, the dog’s entire coat was searched manually. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea allergic dogs in the flea study. Palatability was assessed in both studies. Simparica Trio™ was well tolerated in both studies. Efficacy against fleas was ≥ 97.9% in the Simparica Trio™ group and ≥ 96.1% in the NexGard® Spectra group. Efficacy against ticks was ≥ 94.8% in the Simparica Trio™ group and ≥ 94.4% in the NexGard® Spectra group. Clinical signs of flea allergy dermatitis improved following treatment with Simparica Trio™. Simparica Trio™ Tablets were voluntarily and fully consumed on ≥ 78% of the 485 occasions they were offered. A single oral dose of Simparica Trio™ was safe and highly efficacious against naturally occurring flea and tick infestations for 1 month on dogs. Clinical signs of FAD improved following treatment. Simparica Trio™ was voluntarily and readily consumed by most dogs.
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efficacy of a new oral Chewable Tablet containing sarolaner moxidectin and pyrantel simparica trio against induced ascarid infections in dogs
Parasites & Vectors, 2020Co-Authors: Csilla Becskei, Susan J Holzmer, Kristina Kryda, Mirjan Thys, Laurel Bowersock, Tiago Fernandes, Leon Meyer, Craig R Reinemeyer, Sean P MahabirAbstract:Ascarid infections are among the most prevalent intestinal parasitic infections occurring in dogs around the world, with Toxocara canis and Toxascaris leonina commonly observed. Toxocara canis can cause considerable disease in dogs and humans, and year-round prophylactic treatment and control in dogs is recommended. Elimination of immature stages of these parasites before egg-laying will reduce environmental contamination and the risk of infection for both dogs and humans. Studies were conducted to evaluate the efficacy of a novel, oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced immature adult (L5) and adult T. canis, and adult T. leonina infections in dogs. Six negative-controlled, masked, randomized laboratory studies were conducted. Two studies each evaluated efficacy against immature adult (L5) T. canis, adult T. canis, and adult T. leonina. Sixteen to 40 dogs were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo Tablets or Simparica Trio™ Tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy was based on the number of worms recovered at necropsy 7–10 days after treatment compared to placebo control. Based on geometric mean worm counts, efficacy of the sarolaner + moxidectin + pyrantel combination was ≥ 95.2% against immature adult T. canis, ≥ 97.3% against adult T. canis, and ≥ 89.7% against adult T. leonina. There were no treatment-related adverse events in any study. These studies confirm the efficacy of a single dose of a new oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against immature adult and adult T. canis, and adult T. leonina infections in dogs.
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Efficacy of a new oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced ascarid infections in dogs
Parasites & Vectors, 2020Co-Authors: Csilla Becskei, Susan J Holzmer, Kristina Kryda, Mirjan Thys, Laurel Bowersock, Tiago Fernandes, Leon Meyer, Craig R Reinemeyer, Sean P MahabirAbstract:Background Ascarid infections are among the most prevalent intestinal parasitic infections occurring in dogs around the world, with Toxocara canis and Toxascaris leonina commonly observed. Toxocara canis can cause considerable disease in dogs and humans, and year-round prophylactic treatment and control in dogs is recommended. Elimination of immature stages of these parasites before egg-laying will reduce environmental contamination and the risk of infection for both dogs and humans. Studies were conducted to evaluate the efficacy of a novel, oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced immature adult (L_5) and adult T. canis , and adult T. leonina infections in dogs. Methods Six negative-controlled, masked, randomized laboratory studies were conducted. Two studies each evaluated efficacy against immature adult (L_5) T. canis , adult T. canis , and adult T. leonina. Sixteen to 40 dogs were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo Tablets or Simparica Trio™ Tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy was based on the number of worms recovered at necropsy 7–10 days after treatment compared to placebo control. Results Based on geometric mean worm counts, efficacy of the sarolaner + moxidectin + pyrantel combination was ≥ 95.2% against immature adult T. canis , ≥ 97.3% against adult T. canis , and ≥ 89.7% against adult T. leonina . There were no treatment-related adverse events in any study. Conclusions These studies confirm the efficacy of a single dose of a new oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against immature adult and adult T. canis , and adult T. leonina infections in dogs.
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efficacy of simparica trio a novel Chewable Tablet containing sarolaner moxidectin and pyrantel against induced hookworm infections in dogs
Parasites & Vectors, 2020Co-Authors: Csilla Becskei, Kristina Kryda, Mirjan Thys, Tiago Fernandes, Leon Meyer, Susanna Martorell, Thomas Geurden, Leentje Dreesen, Sean P MahabirAbstract:Ancylostomatids (‘hookworms’) are among the most important zoonotic nematode parasites infecting dogs worldwide. Ancylostoma caninum and Uncinaria stenocephala are two of the most common hookworm species that infect dogs. Both immature and adult stages of hookworms are voracious blood feeders and can cause death in young dogs before infection can be detected by routine fecal examination. Hence, treatment of both immature and adult stages of hookworms will decrease the risk of important clinical disease in the dog as well as the environmental contamination caused by egg-laying adults, which should reduce the risk of infection for both dogs and humans. The studies presented here were conducted to evaluate the efficacy of a novel, oral Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), against induced larval (L4), immature adult (L5) and adult A. caninum, and adult U. stenocephala infections in dogs. Eight negative-controlled, masked, randomized laboratory studies were conducted. Two separate studies were conducted against each of the target parasites and stages. Sixteen or 18 purpose bred dogs, 8 or 9 in each of the two treatment groups, were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo Tablets or Simparica Trio™ Tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Timing of dosing relative to parasite inoculation allowed for efficacy to be evaluated primarily against the target parasite stage. Worm counts were conducted 7 or 8 days after treatments during necropsy. Efficacy was based on the number of worms recovered at necropsy compared to placebo control. Based on geometric mean worm counts, efficacy of Simparica Trio™ was ≥ 98.4% against L4 larval stage of A. caninum, ≥ 99.8% against immature adult (L5) A. caninum, and 100% against adult A. caninum and adult U. stenocephala. These studies confirm the efficacy of a single oral dose of a novel, Chewable Tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against L4 larval and immature adult (L5) A. caninum, and adult A. caninum and U. stenocephala infections in dogs.
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efficacy of a novel Chewable Tablet containing sarolaner moxidectin and pyrantel simparica trio against four common tick species infesting dogs in europe
Parasites & Vectors, 2020Co-Authors: Csilla Becskei, Julian Liebenberg, Mirjan Thys, Sean P MahabirAbstract:Tick infestations can cause direct deleterious effects to dogs as a result of tick blood-feeding, and indirectly ticks can transmit disease agents that can be detrimental to the health of both dogs and humans. Six laboratory studies were conducted to support dosage selection and efficacy confirmation of a novel combination of sarolaner, moxidectin and pyrantel against four tick species that commonly infest dogs in Europe. Two studies were conducted against Dermacentor reticulatus (one of which was a dose determination study), two against Ixodes ricinus, and one each against Ixodes hexagonus and Rhipicephalus sanguineus (sensu lato). In each study, eight purpose-bred Beagle or mix-breed dogs were randomly allocated to each treatment group and infested with 50 unfed adult ticks on Days-2, 5, 12, 19, 26 and 33. On Day 0 dogs were treated orally with placebo or the combination product. In the dose determination study, dogs received sarolaner at point dosages of 0.6 mg/kg, 1.2 mg/kg or 2.4 mg/kg in combination with moxidectin and pyrantel, and in all other studies dogs received Simparica Trio™ to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt). Efficacy was assessed based on live tick counts conducted 48 hours after treatment and each weekly infestation. There were no treatment-related adverse events in any study. In the dose determination study, 1.2 mg/kg sarolaner was the lowest dosage evaluated that provided > 90% efficacy for at least 28 days and therefore was selected as the dosage to provide tick control for at least one month following a single oral treatment. In the dose confirmation studies, a single oral dose of Simparica Trio™ provided ≥ 99.2% efficacy against existing infestations of all tick species, and against re-infestations efficacy was ≥ 97.2% against D. reticulatus for 28 days and against all other species for 35 days. These studies support the sarolaner dose selected and confirm the efficacy of a single oral dose of Simparica Trio™ against existing infestations and re-infestations of the common tick species infesting dogs in Europe for at least one month.
Barbara Knorr - One of the best experts on this subject based on the ideXlab platform.
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montelukast a leukotriene receptor antagonist for the treatment of persistent asthma in children aged 2 to 5 years
Pediatrics, 2001Co-Authors: Barbara Knorr, Luis Miguel Franchi, Hans Bisgaard, Jan Hendrik Vermeulen, Peter Lesouef, Nancy C Santanello, Theresa Michele, Theodore F Reiss, Ha H Nguyen, Donna L BrattonAbstract:Background. The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been reported. One potential advantage of montelukast is the ease of administering a once-daily Chewable Tablet; additionally, no tachyphylaxis or change in the safety profile has been evidenced after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years, respectively. To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children. Objective. Our primary objective was to determine the safety profile of montelukast, an oral leukotriene receptor antagonist, in preschool children with persistent asthma. Secondarily, the effect of montelukast on exploratory measures of asthma control was also studied. Design and Statistical Analysis. We conducted a double-blind, multicenter, multinational study at 93 centers worldwide: including 56 in the United States, and 21 in countries in Africa, Australia, Europe, North America, and South America. In this study, we randomly assigned 689 patients (aged 2–5 years) to 12 weeks of treatment with placebo (228 patients) or 4 mg of montelukast as a Chewable Tablet (461 patients) after a 2-week placebo baseline period. Patients had a history of physician-diagnosed asthma requiring use of β-agonist and a predefined level of daytime asthma symptoms. Caregivers answered questions twice daily on a validated, asthma-specific diary card and, at specified times during the study, completed a validated asthma-specific quality-of-life questionnaire. Physicians and caregivers completed a global evaluation of asthma control at the end of the study. Efficacy end points included: daytime and overnight asthma symptoms, daily use of β-agonist, days without asthma, frequency of asthma attacks, number of patients discontinued because of asthma, need for rescue medication, physician and caregiver global evaluations of change, asthma-specific caregiver quality of life, and peripheral blood eosinophil counts. Although exploratory, the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding. At screening and at study completion, a complete physical examination was performed. Routine laboratory tests were drawn at screening and weeks 6 and 12, and submitted to a central laboratory for analysis. Adverse effects were collected from caregivers at each clinic visit. An intention-to-treat approach, including all patients with a baseline measurement and at least 1 postrandomization measurement, was performed for all efficacy end points. An analysis-of-variance model with terms for treatment, study center and stratum (inhaled/nebulized corticosteroid use, cromolyn use, or none) was used to estimate treatment group means and between-group differences and to construct 95% confidence intervals. Treatment-by-age, -sex, -race, -radioallergosorbent test, -stratum, and -study center interactions were evaluated by including each term separately. Fisher9s exact test was used for between-group comparisons of the frequency of asthma attacks, discontinuations from the study because of worsening asthma, need for rescue medication, and the frequencies of adverse effects. Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups, an analysis of covariance was performed on the eosinophil change from baseline with the patient9s baseline as covariate. Study Participants. Of the 689 patients enrolled, approximately 60% were boys and 60% were white. Patients were relatively evenly divided by age: 21%, 24%, 30%, and 23% were aged 2, 3, 4, and 5 years, respectively. For 77% of the patients, asthma symptoms first developed during the first 3 years of life. During the placebo baseline period, patients had asthma symptoms on 6.1 days/week and used β-agonist on 6.0 days/week. Results. In over 12 weeks of treatment of patients aged 2 to 5 years, montelukast administered as a 4-mg Chewable Tablet produced significant improvements compared with placebo in multiple parameters of asthma control including: daytime asthma symptoms (cough, wheeze, trouble breathing, and activity limitation); overnight asthma symptoms (cough); the percentage of days with asthma symptoms; the percentage of days without asthma; the need for β-agonist or oral corticosteroids; physician global evaluations; and peripheral blood eosinophils. The clinical benefit of montelukast was evident within 1 day of starting therapy. Improvements in asthma control were consistent across age, sex, race, and study center, and whether or not patients had a positive radioallergosorbent test. Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy. Caregiver global evaluations, the percentage of patients experiencing asthma attacks, and improvements in quality-of-life scores favored montelukast, but were not significantly different from placebo. There were no clinically meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects, with the exception of asthma, which occurred significantly more frequently in the placebo group. There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels. Approximately 90% of the patients completed the study. Conclusions. Oral montelukast (4-mg Chewable Tablet) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinically important adverse effects. Similarly, in adults and children aged 6 to 14 years, montelukast improves multiple parameters of asthma control. Thus, this study confirms and extends the benefit of montelukast to younger children with persistent asthma.
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montelukast a leukotriene receptor antagonist for the treatment of persistent asthma in children aged 2 to 5 years
Pediatrics, 2001Co-Authors: Barbara Knorr, Luis Miguel Franchi, Hans Bisgaard, Jan Hendrik Vermeulen, Peter Lesouef, Nancy C Santanello, Theresa Michele, Theodore F Reiss, Ha H Nguyen, Donna L BrattonAbstract:Background. The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been reported. One potential advantage of montelukast is the ease of administering a once-daily Chewable Tablet; additionally, no tachyphylaxis or change in the safety profile has been evidenced after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years, respectively. To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children. Objective. Our primary objective was to determine the safety profile of montelukast, an oral leukotriene receptor antagonist, in preschool children with persistent asthma. Secondarily, the effect of montelukast on exploratory measures of asthma control was also studied. Design and Statistical Analysis. We conducted a double-blind, multicenter, multinational study at 93 centers worldwide: including 56 in the United States, and 21 in countries in Africa, Australia, Europe, North America, and South America. In this study, we randomly assigned 689 patients (aged 2–5 years) to 12 weeks of treatment with placebo (228 patients) or 4 mg of montelukast as a Chewable Tablet (461 patients) after a 2-week placebo baseline period. Patients had a history of physician-diagnosed asthma requiring use of β-agonist and a predefined level of daytime asthma symptoms. Caregivers answered questions twice daily on a validated, asthma-specific diary card and, at specified times during the study, completed a validated asthma-specific quality-of-life questionnaire. Physicians and caregivers completed a global evaluation of asthma control at the end of the study. Efficacy end points included: daytime and overnight asthma symptoms, daily use of β-agonist, days without asthma, frequency of asthma attacks, number of patients discontinued because of asthma, need for rescue medication, physician and caregiver global evaluations of change, asthma-specific caregiver quality of life, and peripheral blood eosinophil counts. Although exploratory, the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding. At screening and at study completion, a complete physical examination was performed. Routine laboratory tests were drawn at screening and weeks 6 and 12, and submitted to a central laboratory for analysis. Adverse effects were collected from caregivers at each clinic visit. An intention-to-treat approach, including all patients with a baseline measurement and at least 1 postrandomization measurement, was performed for all efficacy end points. An analysis-of-variance model with terms for treatment, study center and stratum (inhaled/nebulized corticosteroid use, cromolyn use, or none) was used to estimate treatment group means and between-group differences and to construct 95% confidence intervals. Treatment-by-age, -sex, -race, -radioallergosorbent test, -stratum, and -study center interactions were evaluated by including each term separately. Fisher9s exact test was used for between-group comparisons of the frequency of asthma attacks, discontinuations from the study because of worsening asthma, need for rescue medication, and the frequencies of adverse effects. Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups, an analysis of covariance was performed on the eosinophil change from baseline with the patient9s baseline as covariate. Study Participants. Of the 689 patients enrolled, approximately 60% were boys and 60% were white. Patients were relatively evenly divided by age: 21%, 24%, 30%, and 23% were aged 2, 3, 4, and 5 years, respectively. For 77% of the patients, asthma symptoms first developed during the first 3 years of life. During the placebo baseline period, patients had asthma symptoms on 6.1 days/week and used β-agonist on 6.0 days/week. Results. In over 12 weeks of treatment of patients aged 2 to 5 years, montelukast administered as a 4-mg Chewable Tablet produced significant improvements compared with placebo in multiple parameters of asthma control including: daytime asthma symptoms (cough, wheeze, trouble breathing, and activity limitation); overnight asthma symptoms (cough); the percentage of days with asthma symptoms; the percentage of days without asthma; the need for β-agonist or oral corticosteroids; physician global evaluations; and peripheral blood eosinophils. The clinical benefit of montelukast was evident within 1 day of starting therapy. Improvements in asthma control were consistent across age, sex, race, and study center, and whether or not patients had a positive radioallergosorbent test. Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy. Caregiver global evaluations, the percentage of patients experiencing asthma attacks, and improvements in quality-of-life scores favored montelukast, but were not significantly different from placebo. There were no clinically meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects, with the exception of asthma, which occurred significantly more frequently in the placebo group. There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels. Approximately 90% of the patients completed the study. Conclusions. Oral montelukast (4-mg Chewable Tablet) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinically important adverse effects. Similarly, in adults and children aged 6 to 14 years, montelukast improves multiple parameters of asthma control. Thus, this study confirms and extends the benefit of montelukast to younger children with persistent asthma.
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montelukast once daily inhibits exercise induced bronchoconstriction in 6 to 14 year old children with asthma
The Journal of Pediatrics, 1998Co-Authors: James P Kemp, Theodore F Reiss, Ha H Nguyen, Robert J Dockhorn, Gail G Shapiro, Beth C Seidenberg, Barbara KnorrAbstract:Abstract Objective: To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma. Study design: Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV 1 ) ≥70% of the predicted value and a fall in FEV 1 ≥ 20% after exercise on 2 occasions. Patients received montelukast (5-mg Chewable Tablet) or placebo once daily in the evening for 2 days in crossover fashion (at least 4 days between treatment periods). Standardized exercise challenges were performed 20 to 24 hours after the last dose in each period. End points included area above the postexercise percent fall in FEV 1 versus time curve (AAC 0-60min ), maximum percent fall in FEV 1 from pre-exercise baseline, and time to recovery of FEV 1 to within 5% of pre-exercise baseline. Results: Montelukast significantly reduced AAC 0-60min (265 vs 590 % · min for montelukast and placebo, respectively, P ≤ .05; ~59% protection relative to placebo) and the maximum percent fall (18% vs 26% for montelukast and placebo, respectively, P ≤ .05). Montelukast treatment resulted in a shorter time to recovery (18 vs 28 minutes for montelukast and placebo, respectively, P = .079). Conclusions: Montelukast attenuates EIB at the end of the dosing interval in 6- to 14-year-old children with asthma. (J Pediatr 1998;133:424-8)
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montelukast once daily inhibits exercise induced bronchoconstriction in 6 to 14 year old children with asthma
The Journal of Pediatrics, 1998Co-Authors: James P Kemp, Theodore F Reiss, Ha H Nguyen, Robert J Dockhorn, Gail G Shapiro, Beth C Seidenberg, Barbara KnorrAbstract:Abstract Objective: To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma. Study design: Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV 1 ) ≥70% of the predicted value and a fall in FEV 1 ≥ 20% after exercise on 2 occasions. Patients received montelukast (5-mg Chewable Tablet) or placebo once daily in the evening for 2 days in crossover fashion (at least 4 days between treatment periods). Standardized exercise challenges were performed 20 to 24 hours after the last dose in each period. End points included area above the postexercise percent fall in FEV 1 versus time curve (AAC 0-60min ), maximum percent fall in FEV 1 from pre-exercise baseline, and time to recovery of FEV 1 to within 5% of pre-exercise baseline. Results: Montelukast significantly reduced AAC 0-60min (265 vs 590 % · min for montelukast and placebo, respectively, P ≤ .05; ~59% protection relative to placebo) and the maximum percent fall (18% vs 26% for montelukast and placebo, respectively, P ≤ .05). Montelukast treatment resulted in a shorter time to recovery (18 vs 28 minutes for montelukast and placebo, respectively, P = .079). Conclusions: Montelukast attenuates EIB at the end of the dosing interval in 6- to 14-year-old children with asthma. (J Pediatr 1998;133:424-8)
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montelukast for chronic asthma in 6 to 14 year old children a randomized double blind trial
JAMA, 1998Co-Authors: Barbara Knorr, Theodore F Reiss, Beth C Seidenberg, Jonathan Matz, Jonathan A Bernstein, Ha Nguyen, Allan B BeckerAbstract:Context.—Leukotrienes are important mediators of asthma by causing bronchoconstriction, mucous secretion, and increased vascular permeability. Studies using compounds that block leukotrienes have demonstrated improvement in asthma control in adults and adolescents, but children younger than 12 years, for whom asthma is the most common chronic disease, have not been studied.Objective.—To determine the clinical effect of montelukast, a leukotriene receptor antagonist, in 6- to 14-year-old children with asthma.Design.—Eight-week, multicenter, randomized, double-blind study.Setting.—Forty-seven outpatient centers at private practices and academic medical centers in the United States and Canada.Patients.—A total of 336 children with forced expiratory volume in 1 second (FEV1) between 50% to 85% of the predicted value, at least 15% reversibility after inhaled β-agonist administration, a minimal predefined level of daytime asthma symptoms, and daily β-agonist use. Concomitant inhaled corticosteroids at a constant daily dose were used by 39% of patients receiving montelukast and 33% receiving placebo.Intervention.—After a 2-week placebo run-in period, patients received either montelukast (5-mg Chewable Tablet) or matching-image placebo once daily at bedtime for 8 weeks.Main Outcome Measure.—Morning FEV1 percent change from baseline.Results.—Mean morning FEV1 increased from 1.85 L to 2.01 L in the montelukast group and from 1.85 L to 1.93 L in the placebo group. This represents an 8.23% (95% confidence interval [CI], 6.33% to 10.13%) increase from baseline in the montelukast group and a 3.58% (95% CI, 1.29% to 5.87%) increase from baseline in the placebo group (P<.001 for montelukast vs placebo).Conclusion.—Montelukast improves morning FEV1 in 6- to 14-year-old children with chronic asthma.
Ha H Nguyen - One of the best experts on this subject based on the ideXlab platform.
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montelukast a leukotriene receptor antagonist for the treatment of persistent asthma in children aged 2 to 5 years
Pediatrics, 2001Co-Authors: Barbara Knorr, Luis Miguel Franchi, Hans Bisgaard, Jan Hendrik Vermeulen, Peter Lesouef, Nancy C Santanello, Theresa Michele, Theodore F Reiss, Ha H Nguyen, Donna L BrattonAbstract:Background. The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been reported. One potential advantage of montelukast is the ease of administering a once-daily Chewable Tablet; additionally, no tachyphylaxis or change in the safety profile has been evidenced after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years, respectively. To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children. Objective. Our primary objective was to determine the safety profile of montelukast, an oral leukotriene receptor antagonist, in preschool children with persistent asthma. Secondarily, the effect of montelukast on exploratory measures of asthma control was also studied. Design and Statistical Analysis. We conducted a double-blind, multicenter, multinational study at 93 centers worldwide: including 56 in the United States, and 21 in countries in Africa, Australia, Europe, North America, and South America. In this study, we randomly assigned 689 patients (aged 2–5 years) to 12 weeks of treatment with placebo (228 patients) or 4 mg of montelukast as a Chewable Tablet (461 patients) after a 2-week placebo baseline period. Patients had a history of physician-diagnosed asthma requiring use of β-agonist and a predefined level of daytime asthma symptoms. Caregivers answered questions twice daily on a validated, asthma-specific diary card and, at specified times during the study, completed a validated asthma-specific quality-of-life questionnaire. Physicians and caregivers completed a global evaluation of asthma control at the end of the study. Efficacy end points included: daytime and overnight asthma symptoms, daily use of β-agonist, days without asthma, frequency of asthma attacks, number of patients discontinued because of asthma, need for rescue medication, physician and caregiver global evaluations of change, asthma-specific caregiver quality of life, and peripheral blood eosinophil counts. Although exploratory, the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding. At screening and at study completion, a complete physical examination was performed. Routine laboratory tests were drawn at screening and weeks 6 and 12, and submitted to a central laboratory for analysis. Adverse effects were collected from caregivers at each clinic visit. An intention-to-treat approach, including all patients with a baseline measurement and at least 1 postrandomization measurement, was performed for all efficacy end points. An analysis-of-variance model with terms for treatment, study center and stratum (inhaled/nebulized corticosteroid use, cromolyn use, or none) was used to estimate treatment group means and between-group differences and to construct 95% confidence intervals. Treatment-by-age, -sex, -race, -radioallergosorbent test, -stratum, and -study center interactions were evaluated by including each term separately. Fisher9s exact test was used for between-group comparisons of the frequency of asthma attacks, discontinuations from the study because of worsening asthma, need for rescue medication, and the frequencies of adverse effects. Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups, an analysis of covariance was performed on the eosinophil change from baseline with the patient9s baseline as covariate. Study Participants. Of the 689 patients enrolled, approximately 60% were boys and 60% were white. Patients were relatively evenly divided by age: 21%, 24%, 30%, and 23% were aged 2, 3, 4, and 5 years, respectively. For 77% of the patients, asthma symptoms first developed during the first 3 years of life. During the placebo baseline period, patients had asthma symptoms on 6.1 days/week and used β-agonist on 6.0 days/week. Results. In over 12 weeks of treatment of patients aged 2 to 5 years, montelukast administered as a 4-mg Chewable Tablet produced significant improvements compared with placebo in multiple parameters of asthma control including: daytime asthma symptoms (cough, wheeze, trouble breathing, and activity limitation); overnight asthma symptoms (cough); the percentage of days with asthma symptoms; the percentage of days without asthma; the need for β-agonist or oral corticosteroids; physician global evaluations; and peripheral blood eosinophils. The clinical benefit of montelukast was evident within 1 day of starting therapy. Improvements in asthma control were consistent across age, sex, race, and study center, and whether or not patients had a positive radioallergosorbent test. Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy. Caregiver global evaluations, the percentage of patients experiencing asthma attacks, and improvements in quality-of-life scores favored montelukast, but were not significantly different from placebo. There were no clinically meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects, with the exception of asthma, which occurred significantly more frequently in the placebo group. There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels. Approximately 90% of the patients completed the study. Conclusions. Oral montelukast (4-mg Chewable Tablet) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinically important adverse effects. Similarly, in adults and children aged 6 to 14 years, montelukast improves multiple parameters of asthma control. Thus, this study confirms and extends the benefit of montelukast to younger children with persistent asthma.
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montelukast a leukotriene receptor antagonist for the treatment of persistent asthma in children aged 2 to 5 years
Pediatrics, 2001Co-Authors: Barbara Knorr, Luis Miguel Franchi, Hans Bisgaard, Jan Hendrik Vermeulen, Peter Lesouef, Nancy C Santanello, Theresa Michele, Theodore F Reiss, Ha H Nguyen, Donna L BrattonAbstract:Background. The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been reported. One potential advantage of montelukast is the ease of administering a once-daily Chewable Tablet; additionally, no tachyphylaxis or change in the safety profile has been evidenced after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years, respectively. To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children. Objective. Our primary objective was to determine the safety profile of montelukast, an oral leukotriene receptor antagonist, in preschool children with persistent asthma. Secondarily, the effect of montelukast on exploratory measures of asthma control was also studied. Design and Statistical Analysis. We conducted a double-blind, multicenter, multinational study at 93 centers worldwide: including 56 in the United States, and 21 in countries in Africa, Australia, Europe, North America, and South America. In this study, we randomly assigned 689 patients (aged 2–5 years) to 12 weeks of treatment with placebo (228 patients) or 4 mg of montelukast as a Chewable Tablet (461 patients) after a 2-week placebo baseline period. Patients had a history of physician-diagnosed asthma requiring use of β-agonist and a predefined level of daytime asthma symptoms. Caregivers answered questions twice daily on a validated, asthma-specific diary card and, at specified times during the study, completed a validated asthma-specific quality-of-life questionnaire. Physicians and caregivers completed a global evaluation of asthma control at the end of the study. Efficacy end points included: daytime and overnight asthma symptoms, daily use of β-agonist, days without asthma, frequency of asthma attacks, number of patients discontinued because of asthma, need for rescue medication, physician and caregiver global evaluations of change, asthma-specific caregiver quality of life, and peripheral blood eosinophil counts. Although exploratory, the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding. At screening and at study completion, a complete physical examination was performed. Routine laboratory tests were drawn at screening and weeks 6 and 12, and submitted to a central laboratory for analysis. Adverse effects were collected from caregivers at each clinic visit. An intention-to-treat approach, including all patients with a baseline measurement and at least 1 postrandomization measurement, was performed for all efficacy end points. An analysis-of-variance model with terms for treatment, study center and stratum (inhaled/nebulized corticosteroid use, cromolyn use, or none) was used to estimate treatment group means and between-group differences and to construct 95% confidence intervals. Treatment-by-age, -sex, -race, -radioallergosorbent test, -stratum, and -study center interactions were evaluated by including each term separately. Fisher9s exact test was used for between-group comparisons of the frequency of asthma attacks, discontinuations from the study because of worsening asthma, need for rescue medication, and the frequencies of adverse effects. Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups, an analysis of covariance was performed on the eosinophil change from baseline with the patient9s baseline as covariate. Study Participants. Of the 689 patients enrolled, approximately 60% were boys and 60% were white. Patients were relatively evenly divided by age: 21%, 24%, 30%, and 23% were aged 2, 3, 4, and 5 years, respectively. For 77% of the patients, asthma symptoms first developed during the first 3 years of life. During the placebo baseline period, patients had asthma symptoms on 6.1 days/week and used β-agonist on 6.0 days/week. Results. In over 12 weeks of treatment of patients aged 2 to 5 years, montelukast administered as a 4-mg Chewable Tablet produced significant improvements compared with placebo in multiple parameters of asthma control including: daytime asthma symptoms (cough, wheeze, trouble breathing, and activity limitation); overnight asthma symptoms (cough); the percentage of days with asthma symptoms; the percentage of days without asthma; the need for β-agonist or oral corticosteroids; physician global evaluations; and peripheral blood eosinophils. The clinical benefit of montelukast was evident within 1 day of starting therapy. Improvements in asthma control were consistent across age, sex, race, and study center, and whether or not patients had a positive radioallergosorbent test. Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy. Caregiver global evaluations, the percentage of patients experiencing asthma attacks, and improvements in quality-of-life scores favored montelukast, but were not significantly different from placebo. There were no clinically meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects, with the exception of asthma, which occurred significantly more frequently in the placebo group. There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels. Approximately 90% of the patients completed the study. Conclusions. Oral montelukast (4-mg Chewable Tablet) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinically important adverse effects. Similarly, in adults and children aged 6 to 14 years, montelukast improves multiple parameters of asthma control. Thus, this study confirms and extends the benefit of montelukast to younger children with persistent asthma.
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montelukast once daily inhibits exercise induced bronchoconstriction in 6 to 14 year old children with asthma
The Journal of Pediatrics, 1998Co-Authors: James P Kemp, Theodore F Reiss, Ha H Nguyen, Robert J Dockhorn, Gail G Shapiro, Beth C Seidenberg, Barbara KnorrAbstract:Abstract Objective: To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma. Study design: Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV 1 ) ≥70% of the predicted value and a fall in FEV 1 ≥ 20% after exercise on 2 occasions. Patients received montelukast (5-mg Chewable Tablet) or placebo once daily in the evening for 2 days in crossover fashion (at least 4 days between treatment periods). Standardized exercise challenges were performed 20 to 24 hours after the last dose in each period. End points included area above the postexercise percent fall in FEV 1 versus time curve (AAC 0-60min ), maximum percent fall in FEV 1 from pre-exercise baseline, and time to recovery of FEV 1 to within 5% of pre-exercise baseline. Results: Montelukast significantly reduced AAC 0-60min (265 vs 590 % · min for montelukast and placebo, respectively, P ≤ .05; ~59% protection relative to placebo) and the maximum percent fall (18% vs 26% for montelukast and placebo, respectively, P ≤ .05). Montelukast treatment resulted in a shorter time to recovery (18 vs 28 minutes for montelukast and placebo, respectively, P = .079). Conclusions: Montelukast attenuates EIB at the end of the dosing interval in 6- to 14-year-old children with asthma. (J Pediatr 1998;133:424-8)
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montelukast once daily inhibits exercise induced bronchoconstriction in 6 to 14 year old children with asthma
The Journal of Pediatrics, 1998Co-Authors: James P Kemp, Theodore F Reiss, Ha H Nguyen, Robert J Dockhorn, Gail G Shapiro, Beth C Seidenberg, Barbara KnorrAbstract:Abstract Objective: To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma. Study design: Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV 1 ) ≥70% of the predicted value and a fall in FEV 1 ≥ 20% after exercise on 2 occasions. Patients received montelukast (5-mg Chewable Tablet) or placebo once daily in the evening for 2 days in crossover fashion (at least 4 days between treatment periods). Standardized exercise challenges were performed 20 to 24 hours after the last dose in each period. End points included area above the postexercise percent fall in FEV 1 versus time curve (AAC 0-60min ), maximum percent fall in FEV 1 from pre-exercise baseline, and time to recovery of FEV 1 to within 5% of pre-exercise baseline. Results: Montelukast significantly reduced AAC 0-60min (265 vs 590 % · min for montelukast and placebo, respectively, P ≤ .05; ~59% protection relative to placebo) and the maximum percent fall (18% vs 26% for montelukast and placebo, respectively, P ≤ .05). Montelukast treatment resulted in a shorter time to recovery (18 vs 28 minutes for montelukast and placebo, respectively, P = .079). Conclusions: Montelukast attenuates EIB at the end of the dosing interval in 6- to 14-year-old children with asthma. (J Pediatr 1998;133:424-8)
Theodore F Reiss - One of the best experts on this subject based on the ideXlab platform.
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montelukast a leukotriene receptor antagonist for the treatment of persistent asthma in children aged 2 to 5 years
Pediatrics, 2001Co-Authors: Barbara Knorr, Luis Miguel Franchi, Hans Bisgaard, Jan Hendrik Vermeulen, Peter Lesouef, Nancy C Santanello, Theresa Michele, Theodore F Reiss, Ha H Nguyen, Donna L BrattonAbstract:Background. The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been reported. One potential advantage of montelukast is the ease of administering a once-daily Chewable Tablet; additionally, no tachyphylaxis or change in the safety profile has been evidenced after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years, respectively. To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children. Objective. Our primary objective was to determine the safety profile of montelukast, an oral leukotriene receptor antagonist, in preschool children with persistent asthma. Secondarily, the effect of montelukast on exploratory measures of asthma control was also studied. Design and Statistical Analysis. We conducted a double-blind, multicenter, multinational study at 93 centers worldwide: including 56 in the United States, and 21 in countries in Africa, Australia, Europe, North America, and South America. In this study, we randomly assigned 689 patients (aged 2–5 years) to 12 weeks of treatment with placebo (228 patients) or 4 mg of montelukast as a Chewable Tablet (461 patients) after a 2-week placebo baseline period. Patients had a history of physician-diagnosed asthma requiring use of β-agonist and a predefined level of daytime asthma symptoms. Caregivers answered questions twice daily on a validated, asthma-specific diary card and, at specified times during the study, completed a validated asthma-specific quality-of-life questionnaire. Physicians and caregivers completed a global evaluation of asthma control at the end of the study. Efficacy end points included: daytime and overnight asthma symptoms, daily use of β-agonist, days without asthma, frequency of asthma attacks, number of patients discontinued because of asthma, need for rescue medication, physician and caregiver global evaluations of change, asthma-specific caregiver quality of life, and peripheral blood eosinophil counts. Although exploratory, the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding. At screening and at study completion, a complete physical examination was performed. Routine laboratory tests were drawn at screening and weeks 6 and 12, and submitted to a central laboratory for analysis. Adverse effects were collected from caregivers at each clinic visit. An intention-to-treat approach, including all patients with a baseline measurement and at least 1 postrandomization measurement, was performed for all efficacy end points. An analysis-of-variance model with terms for treatment, study center and stratum (inhaled/nebulized corticosteroid use, cromolyn use, or none) was used to estimate treatment group means and between-group differences and to construct 95% confidence intervals. Treatment-by-age, -sex, -race, -radioallergosorbent test, -stratum, and -study center interactions were evaluated by including each term separately. Fisher9s exact test was used for between-group comparisons of the frequency of asthma attacks, discontinuations from the study because of worsening asthma, need for rescue medication, and the frequencies of adverse effects. Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups, an analysis of covariance was performed on the eosinophil change from baseline with the patient9s baseline as covariate. Study Participants. Of the 689 patients enrolled, approximately 60% were boys and 60% were white. Patients were relatively evenly divided by age: 21%, 24%, 30%, and 23% were aged 2, 3, 4, and 5 years, respectively. For 77% of the patients, asthma symptoms first developed during the first 3 years of life. During the placebo baseline period, patients had asthma symptoms on 6.1 days/week and used β-agonist on 6.0 days/week. Results. In over 12 weeks of treatment of patients aged 2 to 5 years, montelukast administered as a 4-mg Chewable Tablet produced significant improvements compared with placebo in multiple parameters of asthma control including: daytime asthma symptoms (cough, wheeze, trouble breathing, and activity limitation); overnight asthma symptoms (cough); the percentage of days with asthma symptoms; the percentage of days without asthma; the need for β-agonist or oral corticosteroids; physician global evaluations; and peripheral blood eosinophils. The clinical benefit of montelukast was evident within 1 day of starting therapy. Improvements in asthma control were consistent across age, sex, race, and study center, and whether or not patients had a positive radioallergosorbent test. Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy. Caregiver global evaluations, the percentage of patients experiencing asthma attacks, and improvements in quality-of-life scores favored montelukast, but were not significantly different from placebo. There were no clinically meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects, with the exception of asthma, which occurred significantly more frequently in the placebo group. There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels. Approximately 90% of the patients completed the study. Conclusions. Oral montelukast (4-mg Chewable Tablet) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinically important adverse effects. Similarly, in adults and children aged 6 to 14 years, montelukast improves multiple parameters of asthma control. Thus, this study confirms and extends the benefit of montelukast to younger children with persistent asthma.
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montelukast a leukotriene receptor antagonist for the treatment of persistent asthma in children aged 2 to 5 years
Pediatrics, 2001Co-Authors: Barbara Knorr, Luis Miguel Franchi, Hans Bisgaard, Jan Hendrik Vermeulen, Peter Lesouef, Nancy C Santanello, Theresa Michele, Theodore F Reiss, Ha H Nguyen, Donna L BrattonAbstract:Background. The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been reported. One potential advantage of montelukast is the ease of administering a once-daily Chewable Tablet; additionally, no tachyphylaxis or change in the safety profile has been evidenced after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years, respectively. To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children. Objective. Our primary objective was to determine the safety profile of montelukast, an oral leukotriene receptor antagonist, in preschool children with persistent asthma. Secondarily, the effect of montelukast on exploratory measures of asthma control was also studied. Design and Statistical Analysis. We conducted a double-blind, multicenter, multinational study at 93 centers worldwide: including 56 in the United States, and 21 in countries in Africa, Australia, Europe, North America, and South America. In this study, we randomly assigned 689 patients (aged 2–5 years) to 12 weeks of treatment with placebo (228 patients) or 4 mg of montelukast as a Chewable Tablet (461 patients) after a 2-week placebo baseline period. Patients had a history of physician-diagnosed asthma requiring use of β-agonist and a predefined level of daytime asthma symptoms. Caregivers answered questions twice daily on a validated, asthma-specific diary card and, at specified times during the study, completed a validated asthma-specific quality-of-life questionnaire. Physicians and caregivers completed a global evaluation of asthma control at the end of the study. Efficacy end points included: daytime and overnight asthma symptoms, daily use of β-agonist, days without asthma, frequency of asthma attacks, number of patients discontinued because of asthma, need for rescue medication, physician and caregiver global evaluations of change, asthma-specific caregiver quality of life, and peripheral blood eosinophil counts. Although exploratory, the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding. At screening and at study completion, a complete physical examination was performed. Routine laboratory tests were drawn at screening and weeks 6 and 12, and submitted to a central laboratory for analysis. Adverse effects were collected from caregivers at each clinic visit. An intention-to-treat approach, including all patients with a baseline measurement and at least 1 postrandomization measurement, was performed for all efficacy end points. An analysis-of-variance model with terms for treatment, study center and stratum (inhaled/nebulized corticosteroid use, cromolyn use, or none) was used to estimate treatment group means and between-group differences and to construct 95% confidence intervals. Treatment-by-age, -sex, -race, -radioallergosorbent test, -stratum, and -study center interactions were evaluated by including each term separately. Fisher9s exact test was used for between-group comparisons of the frequency of asthma attacks, discontinuations from the study because of worsening asthma, need for rescue medication, and the frequencies of adverse effects. Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups, an analysis of covariance was performed on the eosinophil change from baseline with the patient9s baseline as covariate. Study Participants. Of the 689 patients enrolled, approximately 60% were boys and 60% were white. Patients were relatively evenly divided by age: 21%, 24%, 30%, and 23% were aged 2, 3, 4, and 5 years, respectively. For 77% of the patients, asthma symptoms first developed during the first 3 years of life. During the placebo baseline period, patients had asthma symptoms on 6.1 days/week and used β-agonist on 6.0 days/week. Results. In over 12 weeks of treatment of patients aged 2 to 5 years, montelukast administered as a 4-mg Chewable Tablet produced significant improvements compared with placebo in multiple parameters of asthma control including: daytime asthma symptoms (cough, wheeze, trouble breathing, and activity limitation); overnight asthma symptoms (cough); the percentage of days with asthma symptoms; the percentage of days without asthma; the need for β-agonist or oral corticosteroids; physician global evaluations; and peripheral blood eosinophils. The clinical benefit of montelukast was evident within 1 day of starting therapy. Improvements in asthma control were consistent across age, sex, race, and study center, and whether or not patients had a positive radioallergosorbent test. Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy. Caregiver global evaluations, the percentage of patients experiencing asthma attacks, and improvements in quality-of-life scores favored montelukast, but were not significantly different from placebo. There were no clinically meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects, with the exception of asthma, which occurred significantly more frequently in the placebo group. There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels. Approximately 90% of the patients completed the study. Conclusions. Oral montelukast (4-mg Chewable Tablet) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinically important adverse effects. Similarly, in adults and children aged 6 to 14 years, montelukast improves multiple parameters of asthma control. Thus, this study confirms and extends the benefit of montelukast to younger children with persistent asthma.
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montelukast once daily inhibits exercise induced bronchoconstriction in 6 to 14 year old children with asthma
The Journal of Pediatrics, 1998Co-Authors: James P Kemp, Theodore F Reiss, Ha H Nguyen, Robert J Dockhorn, Gail G Shapiro, Beth C Seidenberg, Barbara KnorrAbstract:Abstract Objective: To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma. Study design: Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV 1 ) ≥70% of the predicted value and a fall in FEV 1 ≥ 20% after exercise on 2 occasions. Patients received montelukast (5-mg Chewable Tablet) or placebo once daily in the evening for 2 days in crossover fashion (at least 4 days between treatment periods). Standardized exercise challenges were performed 20 to 24 hours after the last dose in each period. End points included area above the postexercise percent fall in FEV 1 versus time curve (AAC 0-60min ), maximum percent fall in FEV 1 from pre-exercise baseline, and time to recovery of FEV 1 to within 5% of pre-exercise baseline. Results: Montelukast significantly reduced AAC 0-60min (265 vs 590 % · min for montelukast and placebo, respectively, P ≤ .05; ~59% protection relative to placebo) and the maximum percent fall (18% vs 26% for montelukast and placebo, respectively, P ≤ .05). Montelukast treatment resulted in a shorter time to recovery (18 vs 28 minutes for montelukast and placebo, respectively, P = .079). Conclusions: Montelukast attenuates EIB at the end of the dosing interval in 6- to 14-year-old children with asthma. (J Pediatr 1998;133:424-8)
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montelukast once daily inhibits exercise induced bronchoconstriction in 6 to 14 year old children with asthma
The Journal of Pediatrics, 1998Co-Authors: James P Kemp, Theodore F Reiss, Ha H Nguyen, Robert J Dockhorn, Gail G Shapiro, Beth C Seidenberg, Barbara KnorrAbstract:Abstract Objective: To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma. Study design: Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV 1 ) ≥70% of the predicted value and a fall in FEV 1 ≥ 20% after exercise on 2 occasions. Patients received montelukast (5-mg Chewable Tablet) or placebo once daily in the evening for 2 days in crossover fashion (at least 4 days between treatment periods). Standardized exercise challenges were performed 20 to 24 hours after the last dose in each period. End points included area above the postexercise percent fall in FEV 1 versus time curve (AAC 0-60min ), maximum percent fall in FEV 1 from pre-exercise baseline, and time to recovery of FEV 1 to within 5% of pre-exercise baseline. Results: Montelukast significantly reduced AAC 0-60min (265 vs 590 % · min for montelukast and placebo, respectively, P ≤ .05; ~59% protection relative to placebo) and the maximum percent fall (18% vs 26% for montelukast and placebo, respectively, P ≤ .05). Montelukast treatment resulted in a shorter time to recovery (18 vs 28 minutes for montelukast and placebo, respectively, P = .079). Conclusions: Montelukast attenuates EIB at the end of the dosing interval in 6- to 14-year-old children with asthma. (J Pediatr 1998;133:424-8)
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montelukast for chronic asthma in 6 to 14 year old children a randomized double blind trial
JAMA, 1998Co-Authors: Barbara Knorr, Theodore F Reiss, Beth C Seidenberg, Jonathan Matz, Jonathan A Bernstein, Ha Nguyen, Allan B BeckerAbstract:Context.—Leukotrienes are important mediators of asthma by causing bronchoconstriction, mucous secretion, and increased vascular permeability. Studies using compounds that block leukotrienes have demonstrated improvement in asthma control in adults and adolescents, but children younger than 12 years, for whom asthma is the most common chronic disease, have not been studied.Objective.—To determine the clinical effect of montelukast, a leukotriene receptor antagonist, in 6- to 14-year-old children with asthma.Design.—Eight-week, multicenter, randomized, double-blind study.Setting.—Forty-seven outpatient centers at private practices and academic medical centers in the United States and Canada.Patients.—A total of 336 children with forced expiratory volume in 1 second (FEV1) between 50% to 85% of the predicted value, at least 15% reversibility after inhaled β-agonist administration, a minimal predefined level of daytime asthma symptoms, and daily β-agonist use. Concomitant inhaled corticosteroids at a constant daily dose were used by 39% of patients receiving montelukast and 33% receiving placebo.Intervention.—After a 2-week placebo run-in period, patients received either montelukast (5-mg Chewable Tablet) or matching-image placebo once daily at bedtime for 8 weeks.Main Outcome Measure.—Morning FEV1 percent change from baseline.Results.—Mean morning FEV1 increased from 1.85 L to 2.01 L in the montelukast group and from 1.85 L to 1.93 L in the placebo group. This represents an 8.23% (95% confidence interval [CI], 6.33% to 10.13%) increase from baseline in the montelukast group and a 3.58% (95% CI, 1.29% to 5.87%) increase from baseline in the placebo group (P<.001 for montelukast vs placebo).Conclusion.—Montelukast improves morning FEV1 in 6- to 14-year-old children with chronic asthma.