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Mariëlle Eerdekens - One of the best experts on this subject based on the ideXlab platform.
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a comparison of serum prolactin concentrations after administration of Paliperidone extended release and risperidone tablets in patients with schizophrenia
Journal of Psychopharmacology, 2010Co-Authors: Joris Berwaerts, S Boom, A Cleton, K Talluri, Luc Janssens, Bart Remmerie, Michelle Kramer, Stefaan Rossenu, Mariëlle EerdekensAbstract:Increases in serum prolactin concentrations after administration of risperidone have been attributed, by some, to the availability of Paliperidone in plasma. This double-blind, randomized, parallel-group study in patients with schizophrenia compared serum prolactin concentrations following the administration of Paliperidone extended-release and risperidone immediate-release tablets. At steady state, the doses administered resulted in a similar exposure to Paliperidone and the pharmacologically active fraction of risperidone (i.e. risperidone + Paliperidone), respectively. Eligible patients were randomized to either Paliperidone extended-release 12 mg on days 1-6 or risperidone immediate-release 2 mg on day 1 and 4 mg on days 2-6. Mean serum prolactin concentrations increased on day 1 (C(max): 71.8 ng/ml and 89.7 ng/ml reached at 6.5 hours and 2.6 hours for Paliperidone extended-release and risperidone immediate-release, respectively). On day 6, serum prolactin concentration-time profiles were similar for both treatments, with overall higher serum prolactin concentrations than on day 1 (AUC(0-24 h): 1389 and 842 ng h/ml, and 1306 and 741 ng.h/ml on day 6 and day 1 for Paliperidone extended-release and risperidone immediate-release, respectively). These results indicate that Paliperidone extended-release 12 mg and risperidone immediate-release 4 mg, administered over a period of 6 days, lead to similar elevations in serum prolactin concentrations.
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Paliperidone palmitate maintenance treatment in delaying the time to relapse in patients with schizophrenia a randomized double blind placebo controlled study
Schizophrenia Research, 2010Co-Authors: David Hough, Srihari Gopal, Ujjwala Vijapurkar, Margarita Morozova, Mariëlle EerdekensAbstract:Abstract Objective We assessed efficacy and tolerability of the injectable atypical antipsychotic Paliperidone palmitate in delaying time-to-relapse in adults with schizophrenia. Methods Eligible patients (Positive and Negative Syndrome Scale [PANSS] total score Results The preplanned interim analysis (conducted after 68 relapse events) included 312 patients: mean age = 40 years, 55% men, 66% white, and mean transition baseline PANSS total score (SD): placebo, 69.5 (16.89); Paliperidone palmitate, 69.3 (17.39). Time-to-relapse (primary endpoint) favored Paliperidone palmitate (p Conclusion Paliperidone palmitate significantly delayed time-to-relapse compared with placebo and presented no new safety signals.
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single and multiple dose pharmacokinetics and dose proportionality of the psychotropic agent Paliperidone extended release
The Journal of Clinical Pharmacology, 2009Co-Authors: S Boom, K Talluri, Mariëlle Eerdekens, Luc Janssens, Bart Remmerie, Marc De Meulder, S Rossenu, Nancy Van Osselaer, A CletonAbstract:Paliperidone extended-release tablet (Paliperidone ER) is a centrally active dopamine D 2 - and serotonergic 5-HT 2A -receptor antagonist that is registered for the treatment of schizophrenia. The controlled rate of release of Paliperidone from the ER formulation is designed to have a slower absorption rate, which results in gradual ascending plasma concentrations with observed maximum plasma concentrations occurring at 24 hours after dosing on the first dosing day. On subsequent treatment days, the ER formulation provides minimal fluctuations in plasma concentrations. Paliperidone is eliminated with a terminal half-life of approximately 24 hours. Steady state is achieved after 4 daily doses. Paliperidone ER exhibits time-invariant pharmacokinetics. It shows a 3.5-fold accumulation upon steady state, mainly caused by the controlled release characteristics of the formulation. Paliperidone ER displays dose proportionality over the dose range of 3 to 15 mg; the 90% confidence intervals of the pairwise dose comparisons are all included in the 80% to 125% bioequivalence limits.
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The influence of hepatic impairment on the pharmacokinetics of Paliperidone.
Int. Journal of Clinical Pharmacology and Therapeutics, 2009Co-Authors: S Boom, A Thyssen, Herta Crauwels, A Cleton, L Janssens, K Talluri, Mariëlle EerdekensAbstract:Objectives: This study assessed the impact of hepatic impairment on the pharmacokinetics (PK) of Paliperidone and its enantiomers. Methods: A single 1 mg dose of Paliperidone immediate-release (IR) was administered to subjects with moderate hepatic impairment (n = 10) and demographically matched individuals with normal hepatic function (n = 10). Results: Plasma protein binding was lower in hepatically impaired subjects resulting in a 27% higher unbound fraction of Paliperidone compared with healthy individuals. After correcting for the difference in plasma protein binding, unbound exposures were comparable between groups. All other PK parameters were similar between the two groups. Paliperidone IR was equally well tolerated in both groups. Conclusions: The impact of moderate hepatic impairment on Paliperidone PK is not considered clinically relevant as the PK profile of unbound Paliperidone is similar for subjects with moderate hepatic impairment and those with normal hepatic function. Dosage adjustments of Paliperidone are not required in subjects with mild or moderate hepatic impairment.
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The effects of paroxetine on the pharmacokinetics of Paliperidone extended-release tablets.
Pharmacopsychiatry, 2009Co-Authors: Joris Berwaerts, A Cleton, V. Herben, I. Van De Vliet, I. Chang, P. Van Hoek, Mariëlle EerdekensAbstract:INTRODUCTION Co-morbid medical and psychiatric conditions are common in individuals with schizophrenia. As such, selecting antipsychotic medications with a low potential for drug-drug interactions (DDIs) is crucial, as many are extensively metabolized by hepatic cytochrome P450 (CYP) isozymes. METHODS This randomized, crossover study examined the effects of paroxetine (a potent CYP2D6 inhibitor) on the pharmacokinetic parameters of a single dose of the novel antipsychotic agent, Paliperidone extended-release tablets (Paliperidone ER), in healthy subjects. RESULTS The mean C (max) and AUC of Paliperidone were slightly higher and Paliperidone clearance was slightly lower following co-administration of Paliperidone ER with paroxetine. There was a ratio of geometric treatment means of 116.48% for AUC (infinity) [90% CI: 104.49-129.84]. However, the increase in total exposure to Paliperidone was not considered clinically relevant. The incidence of adverse events was lower when subjects received the combination of Paliperidone ER and paroxetine compared with paroxetine alone. DISCUSSION Results suggest that no clinically relevant pharmacokinetic interaction occurs when paroxetine and Paliperidone ER are co-administered and, therefore, initiation or discontinuation of concomitant treatment with CYP2D6-inhibiting drugs does not appear to warrant an adjustment in Paliperidone ER dosage.
Pilar Lim - One of the best experts on this subject based on the ideXlab platform.
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a randomized placebo and active controlled study of Paliperidone extended release as maintenance treatment in patients with bipolar i disorder after an acute manic or mixed episode
Journal of Affective Disorders, 2012Co-Authors: Joris Berwaerts, Isaac Nuamah, Rama Melkote, Pilar LimAbstract:Abstract Background Paliperidone ER monotherapy was efficacious in treating acute mania in two 3-week studies in patients with bipolar I disorder. We assessed its efficacy in a study investigating maintenance treatment of clinically stable patients with this disorder. Methods Patients (n = 766), aged 18 to 65 years inclusive, with current manic or mixed episodes were initially randomized (4:1) to flexibly-dosed Paliperidone ER (3–12 mg/day) or olanzapine (5–20 mg/day; 3-week acute treatment phase); responders continued the same treatment (12-week continuation phase). Patients on Paliperidone ER who achieved remission during this phase were randomized (1:1) to fixed-dose Paliperidone ER (n = 152) or placebo (n = 148); those on olanzapine continued to receive that at fixed dose (n = 83) (maintenance phase). Results Median time to recurrence of any mood symptoms (primary endpoint) was: 558 days (Paliperidone ER), 283 days (placebo) and not observed with olanzapine ( Limitations Responder-enriched design prevents extrapolation of data to patients not previously stabilized on Paliperidone ER. Conclusions Paliperidone ER significantly delayed the time to recurrence of any mood symptoms, versus placebo, in patients with bipolar I disorder. No new safety concerns emerged.
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a randomized placebo and active controlled study of Paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar i disorder
Bipolar Disorders, 2010Co-Authors: Eduard Vieta, Pilar Lim, Isaac Nuamah, Eric Yuen, Joseph Palumbo, David Hough, Joris BerwaertsAbstract:Vieta E, Nuamah IF, Lim P, Yuen EC, Palumbo JM, Hough DW, Berwaerts J. A randomized, placebo- and active-controlled study of Paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder. Bipolar Disord 2010: 12: 230–243. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: To evaluate the antimanic efficacy and safety of Paliperidone extended-release (ER) tablets in patients with bipolar I disorder. Methods: This study included a 3-week, double-blind, acute treatment phase (Paliperidone ER versus placebo, with quetiapine as control), and a 9-week, double-blind, maintenance phase (Paliperidone ER versus quetiapine). Patients [n = 493; Young Mania Rating Scale (YMRS) score ≥ 20] were randomized (2:2:1) to flexibly dosed Paliperidone ER (3–12 mg/day), quetiapine (400–800 mg/day), or placebo for the acute treatment phase. During the maintenance phase, patients assigned to placebo were switched to Paliperidone ER but not included in analysis of efficacy. Results: Paliperidone ER was superior to placebo at the 3-week endpoint {primary outcome; least-squares mean difference in change from baseline in YMRS scores [95% confidence interval (CI)]: −5.5 (−7.57; −3.35); p < 0.001} and noninferior to quetiapine at the 12-week endpoint [least-squares mean difference (95% CI): 1.7 (−0.47; 3.96)]. The median mode dose during the 12-week treatment period was 9 mg for Paliperidone ER and 600 mg for quetiapine. The most common (≥ 10%) treatment-emergent adverse events during the 12-week period were: headache (16%), somnolence (10%), and akathisia (10%) for Paliperidone ER; somnolence (21%), sedation and dry mouth (17% each), headache (14%), and dizziness (13%) for quetiapine. Body weight increase ≥ 7% from baseline to 12-week endpoint was 8% with Paliperidone ER and 17% with quetiapine. A higher percentage of Paliperidone ER (13.9%) versus quetiapine patients (7.5%) ‘switched to depression’ at the12-week endpoint. Conclusions: Paliperidone ER (3–12 mg/day) was efficacious and tolerable in the treatment of acute mania.
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safety and tolerability of oral Paliperidone extended release tablets in elderly patients with schizophrenia a double blind placebo controlled study with six month open label extension
American Journal of Geriatric Psychiatry, 2008Co-Authors: Andreas Tzimos, Michelle Kramer, Lisa Ford, Pilar Lim, Cristiana Gassmannmayer, Viktor Samokhvalov, Mariëlle EerdekensAbstract:Objective The objective of this multicenter, international study was to evaluate safety and tolerability of Paliperidone extended-release (ER) tablets in elderly (age ≥65 years) patients with schizophrenia. The authors conducted a 6-week, double-blind, randomized, placebo-controlled, optional 24-week open-label extension study. Interventions consisted of flexible, once-daily doses of Paliperidone ER (3–12 mg/day; 6-mg starting dose, adjusted in 3-mg dose increments) or placebo (2:1) during double-blind treatment and Paliperidone ER only during open-label treatment. Measurements included adverse events, laboratory tests, physical examinations, 12-lead electrocardiograms, movement disorder rating scales, Positive and Negative Syndrome Scale, and Clinical Global Impression scale. The study was not powered to show statistical differences. Results Patients (N = 114) were predominantly female (73%); mean age was 70 years (double-blind phase). Concomitant disease presence was consistent with that of an older population. During the double-blind phase, discontinuation rates resulting from adverse events were similar between groups (Paliperidone ER: 7%, placebo: 8%) as were incidences of treatment-emergent adverse events (Paliperidone ER: 67%, placebo: 71%). Serious adverse events occurred in 3% of the Paliperidone ER- and 8% of the placebo-treated patients. Elevated prolactin levels occurred in approximately one half of patients. No prolactin- or glucose treatment-related adverse events or noteworthy mean changes in body weight (0 kg [standard deviation: 2.1] and 0 kg [standard deviation: 2.3] for Paliperidone ER and placebo, respectively) were observed. Safety and tolerability results in the extension were consistent with the shorter-term results. Efficacy measures did not show consistent statistical improvement between treatment groups. Conclusion Paliperidone ER (3–12 mg/day) treatment over a 30-week period was generally well-tolerated and may improve symptom severity in elderly patients with schizophrenia.
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efficacy and safety of Paliperidone extended release tablets results of a 6 week randomized placebo controlled study
Biological Psychiatry, 2007Co-Authors: Stephen R Marder, Mariëlle Eerdekens, Michelle Kramer, Lisa Ford, Els Eerdekens, Pilar Lim, Adam LowyAbstract:Background Paliperidone extended-release tablet (Paliperidone ER; Invega, Janssen L.P., Titusville, New Jersey) is an oral psychotropic for schizophrenia treatment. Methods Efficacy and safety of once-daily Paliperidone ER (6 and 12 mg) were assessed versus placebo in 444 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. An olanzapine (10 mg) treatment arm was included to confirm trial validity. Results Both doses of Paliperidone ER demonstrated significant improvement in Positive and Negative Syndrome Scale (PANSS) total score ( p ≤ .006) and certain PANSS Marder factor scores compared with placebo ( p ≤ .025); PANSS total score also improved in the olanzapine treatment arm. Paliperidone ER 6 mg ( p ≤ .008), but not 12 mg, was associated with significant improvements in personal and social performance. The incidence of treatment-emergent adverse events (AEs) for Paliperidone ER 6 mg was comparable with placebo and slightly greater with Paliperidone ER 12 mg. Changes in blood glucose and lipid levels with Paliperidone ER were comparable with placebo. Two patients treated with Paliperidone ER experienced glucose-related AEs. Body-weight increases of 1-2 kg were observed with Paliperidone ER. Although there were increases in plasma prolactin levels with Paliperidone ER treatment, the incidence of prolactin-related AEs was ≤1%. Conclusions In this study, Paliperidone ER, particularly the 6-mg dose, was effective and well tolerated, and provides a valuable new treatment option for schizophrenia.
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efficacy safety and early response of Paliperidone extended release tablets Paliperidone er results of a 6 week randomized placebo controlled study
Schizophrenia Research, 2007Co-Authors: Michael H Davidson, Michelle Kramer, Lisa Ford, Pilar Lim, Robin Emsley, Guohua Pan, Mariëlle EerdekensAbstract:Background Paliperidone extended-release tablet (Paliperidone ER) is an oral psychotropic agent developed for schizophrenia treatment. Paliperidone (9-OH-risperidone, metabolite of risperidone), when used with OROS technology has a unique pharmacokinetic profile undergoing limited hepatic metabolism. Methods The efficacy and safety of once-daily Paliperidone ER (3 mg, 9 mg and 15 mg) were compared with placebo in 618 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. An assay sensitivity group with known efficacy was included to confirm trial validity (olanzapine 10 mg). Results All doses of Paliperidone ER demonstrated significant improvements in PANSS total and PANSS factors scores (p < 0.05) and in personal and social functioning (p < 0.001) compared with placebo. Symptom improvement has been observed at the first observation assessment (Day 4) (p < 0.001) compared with placebo, suggesting a rapid onset of action for Paliperidone ER. Paliperidone ER was associated with a low incidence of treatment-emergent adverse events. The incidence of movement disorder-related adverse events and rating scale scores were similar in the Paliperidone ER 3 mg and placebo groups and increased with dose. Increases in prolactin plasma levels and dose-related increases in body weight (< 2 kg) were observed; there were no significant changes in serum lipid or glucose levels. Conclusion In this study, all doses of Paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated. As such, Paliperidone ER may provide a valuable new treatment option for patients with schizophrenia.
Michelle Kramer - One of the best experts on this subject based on the ideXlab platform.
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a comparison of serum prolactin concentrations after administration of Paliperidone extended release and risperidone tablets in patients with schizophrenia
Journal of Psychopharmacology, 2010Co-Authors: Joris Berwaerts, S Boom, A Cleton, K Talluri, Luc Janssens, Bart Remmerie, Michelle Kramer, Stefaan Rossenu, Mariëlle EerdekensAbstract:Increases in serum prolactin concentrations after administration of risperidone have been attributed, by some, to the availability of Paliperidone in plasma. This double-blind, randomized, parallel-group study in patients with schizophrenia compared serum prolactin concentrations following the administration of Paliperidone extended-release and risperidone immediate-release tablets. At steady state, the doses administered resulted in a similar exposure to Paliperidone and the pharmacologically active fraction of risperidone (i.e. risperidone + Paliperidone), respectively. Eligible patients were randomized to either Paliperidone extended-release 12 mg on days 1-6 or risperidone immediate-release 2 mg on day 1 and 4 mg on days 2-6. Mean serum prolactin concentrations increased on day 1 (C(max): 71.8 ng/ml and 89.7 ng/ml reached at 6.5 hours and 2.6 hours for Paliperidone extended-release and risperidone immediate-release, respectively). On day 6, serum prolactin concentration-time profiles were similar for both treatments, with overall higher serum prolactin concentrations than on day 1 (AUC(0-24 h): 1389 and 842 ng h/ml, and 1306 and 741 ng.h/ml on day 6 and day 1 for Paliperidone extended-release and risperidone immediate-release, respectively). These results indicate that Paliperidone extended-release 12 mg and risperidone immediate-release 4 mg, administered over a period of 6 days, lead to similar elevations in serum prolactin concentrations.
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efficacy and tolerability of oral Paliperidone extended release tablets in the treatment of acute schizophrenia pooled data from three 6 week placebo controlled studies
The Journal of Clinical Psychiatry, 2008Co-Authors: Michelle Kramer, Isaac Nuamah, David Hough, Herbert Y Meltzer, William V Bobo, Rosanne Lane, Mariëlle EerdekensAbstract:OBJECTIVE To evaluate the efficacy and safety of an extended-release (ER) formulation of Paliperidone in patients with an acute episode of schizophrenia, in the dosage range of 3 to 15 mg daily. METHOD A pooled analysis of 3 similarly designed 6-week, multicenter, double-blind, randomized, fixed-dose, placebo-controlled studies in 1326 patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score of 70-120) was performed. Patients were randomly assigned to receive 3, 6, 9, 12, or 15 mg daily of Paliperidone ER or placebo. Efficacy and safety assessments were performed. The primary endpoint was change in PANSS total score from baseline to endpoint. RESULTS PANSS total, PANSS subscale factor, and Personal and Social Performance scale scores significantly improved at endpoint for all doses of Paliperidone ER relative to placebo (p
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safety and tolerability of oral Paliperidone extended release tablets in elderly patients with schizophrenia a double blind placebo controlled study with six month open label extension
American Journal of Geriatric Psychiatry, 2008Co-Authors: Andreas Tzimos, Michelle Kramer, Lisa Ford, Pilar Lim, Cristiana Gassmannmayer, Viktor Samokhvalov, Mariëlle EerdekensAbstract:Objective The objective of this multicenter, international study was to evaluate safety and tolerability of Paliperidone extended-release (ER) tablets in elderly (age ≥65 years) patients with schizophrenia. The authors conducted a 6-week, double-blind, randomized, placebo-controlled, optional 24-week open-label extension study. Interventions consisted of flexible, once-daily doses of Paliperidone ER (3–12 mg/day; 6-mg starting dose, adjusted in 3-mg dose increments) or placebo (2:1) during double-blind treatment and Paliperidone ER only during open-label treatment. Measurements included adverse events, laboratory tests, physical examinations, 12-lead electrocardiograms, movement disorder rating scales, Positive and Negative Syndrome Scale, and Clinical Global Impression scale. The study was not powered to show statistical differences. Results Patients (N = 114) were predominantly female (73%); mean age was 70 years (double-blind phase). Concomitant disease presence was consistent with that of an older population. During the double-blind phase, discontinuation rates resulting from adverse events were similar between groups (Paliperidone ER: 7%, placebo: 8%) as were incidences of treatment-emergent adverse events (Paliperidone ER: 67%, placebo: 71%). Serious adverse events occurred in 3% of the Paliperidone ER- and 8% of the placebo-treated patients. Elevated prolactin levels occurred in approximately one half of patients. No prolactin- or glucose treatment-related adverse events or noteworthy mean changes in body weight (0 kg [standard deviation: 2.1] and 0 kg [standard deviation: 2.3] for Paliperidone ER and placebo, respectively) were observed. Safety and tolerability results in the extension were consistent with the shorter-term results. Efficacy measures did not show consistent statistical improvement between treatment groups. Conclusion Paliperidone ER (3–12 mg/day) treatment over a 30-week period was generally well-tolerated and may improve symptom severity in elderly patients with schizophrenia.
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efficacy and safety of Paliperidone extended release tablets results of a 6 week randomized placebo controlled study
Biological Psychiatry, 2007Co-Authors: Stephen R Marder, Mariëlle Eerdekens, Michelle Kramer, Lisa Ford, Els Eerdekens, Pilar Lim, Adam LowyAbstract:Background Paliperidone extended-release tablet (Paliperidone ER; Invega, Janssen L.P., Titusville, New Jersey) is an oral psychotropic for schizophrenia treatment. Methods Efficacy and safety of once-daily Paliperidone ER (6 and 12 mg) were assessed versus placebo in 444 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. An olanzapine (10 mg) treatment arm was included to confirm trial validity. Results Both doses of Paliperidone ER demonstrated significant improvement in Positive and Negative Syndrome Scale (PANSS) total score ( p ≤ .006) and certain PANSS Marder factor scores compared with placebo ( p ≤ .025); PANSS total score also improved in the olanzapine treatment arm. Paliperidone ER 6 mg ( p ≤ .008), but not 12 mg, was associated with significant improvements in personal and social performance. The incidence of treatment-emergent adverse events (AEs) for Paliperidone ER 6 mg was comparable with placebo and slightly greater with Paliperidone ER 12 mg. Changes in blood glucose and lipid levels with Paliperidone ER were comparable with placebo. Two patients treated with Paliperidone ER experienced glucose-related AEs. Body-weight increases of 1-2 kg were observed with Paliperidone ER. Although there were increases in plasma prolactin levels with Paliperidone ER treatment, the incidence of prolactin-related AEs was ≤1%. Conclusions In this study, Paliperidone ER, particularly the 6-mg dose, was effective and well tolerated, and provides a valuable new treatment option for schizophrenia.
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efficacy safety and early response of Paliperidone extended release tablets Paliperidone er results of a 6 week randomized placebo controlled study
Schizophrenia Research, 2007Co-Authors: Michael H Davidson, Michelle Kramer, Lisa Ford, Pilar Lim, Robin Emsley, Guohua Pan, Mariëlle EerdekensAbstract:Background Paliperidone extended-release tablet (Paliperidone ER) is an oral psychotropic agent developed for schizophrenia treatment. Paliperidone (9-OH-risperidone, metabolite of risperidone), when used with OROS technology has a unique pharmacokinetic profile undergoing limited hepatic metabolism. Methods The efficacy and safety of once-daily Paliperidone ER (3 mg, 9 mg and 15 mg) were compared with placebo in 618 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. An assay sensitivity group with known efficacy was included to confirm trial validity (olanzapine 10 mg). Results All doses of Paliperidone ER demonstrated significant improvements in PANSS total and PANSS factors scores (p < 0.05) and in personal and social functioning (p < 0.001) compared with placebo. Symptom improvement has been observed at the first observation assessment (Day 4) (p < 0.001) compared with placebo, suggesting a rapid onset of action for Paliperidone ER. Paliperidone ER was associated with a low incidence of treatment-emergent adverse events. The incidence of movement disorder-related adverse events and rating scale scores were similar in the Paliperidone ER 3 mg and placebo groups and increased with dose. Increases in prolactin plasma levels and dose-related increases in body weight (< 2 kg) were observed; there were no significant changes in serum lipid or glucose levels. Conclusion In this study, all doses of Paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated. As such, Paliperidone ER may provide a valuable new treatment option for patients with schizophrenia.
Carla M Canuso - One of the best experts on this subject based on the ideXlab platform.
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Paliperidone palmitate once monthly reduces risk of relapse of psychotic depressive and manic symptoms and maintains functioning in a double blind randomized study of schizoaffective disorder
The Journal of Clinical Psychiatry, 2015Co-Authors: Ibrahim Turkoz, Jeanpierre Lindenmayer, Carla M Canuso, Bruce R Simonson, David Walling, Nina R Schooler, Larry AlphsAbstract:OBJECTIVE Schizoaffective disorder is a complex illness for which optimal treatment is not well established. Results of the first controlled, relapse-prevention study of Paliperidone palmitate once-monthly injectable (Paliperidone monthly) in schizoaffective disorder are presented. METHOD The study was conducted between September 20, 2010, and October 22, 2013. Patients with schizoaffective disorder (confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders) experiencing acute exacerbation of psychotic and depressive/manic symptoms were stabilized with Paliperidone monthly as monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and randomly assigned (1:1) to Paliperidone monthly or placebo in a 15-month, double-blind, relapse-prevention phase. Randomization was stratified by administration as monotherapy or adjunctive therapy and by study center. The primary endpoint was time to relapse. RESULTS 334 patients were evaluated. Paliperidone monthly significantly delayed time to relapse for psychotic, depressive, and manic symptoms compared with placebo (P < .001, log-rank test). Relapse risk was 2.49 times greater for placebo (hazard ratio = 2.49; 95% CI, 1.55 to 3.99; P < .001, Cox proportional hazards model). Overall relapse rates were 33.5% for placebo and 15.2% for Paliperidone monthly. For monotherapy, relapse risk was 3.38 times greater with placebo (P = .002), and for adjunctive treatment it was 2.03 times greater with placebo (P = .021). Paliperidone monthly was superior to placebo in maintaining functioning as measured by the Personal and Social Performance scale (P = .014, mixed-model repeated-measures analysis). The most common adverse events (placebo, Paliperidone monthly) were increased weight (4.7%, 8.5%), insomnia (7.1%, 4.9%), schizoaffective disorder (5.9%, 3.0%), headache (3.5%, 5.5%), and nasopharyngitis (3.5%, 5.5%). Incidence of any extrapyramidal-related adverse event was 7.1% for placebo and 8.5% for Paliperidone monthly. CONCLUSIONS Paliperidone monthly as monotherapy or adjunctive therapy significantly delayed psychotic, depressive, and/or manic relapses; reduced their risk; and better maintained functioning in patients with schizoaffective disorder. Results support the value of maintenance treatment with Paliperidone monthly in schizoaffective disorder. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01193153.
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Paliperidone er and oral risperidone in patients with schizophrenia a comparative database analysis
BMC Psychiatry, 2011Co-Authors: Ibrahim Turkoz, Cynthia A Bossie, Jeanpierre Lindenmayer, Nina Schooler, Carla M CanusoAbstract:To compare the efficacy and tolerability of Paliperidone extended-release (ER) with risperidone immediate-release using propensity score methodology. Six double-blind, randomized, placebo-controlled, short-term clinical trials for acute schizophrenia with availability of individual patient-level data were identified (3 per compound). Propensity score pairwise matching was used to balance observed covariates between the Paliperidone ER and risperidone patient populations. Scores were generated using logistic regression models, with age, body mass index, race, sex, baseline Positive and Negative Syndrome Scale (PANSS) total score and baseline Clinical Global Impressions–Severity (CGI-S) score as factors. The dosage range of Paliperidone ER (6-12 mg/day) was compared with 2 risperidone dosage ranges: 2-4 and 4-6 mg/day. The primary efficacy measure was change in PANSS total score at week 6 end point. Tolerability end points included adverse event (AE) reports and weight. AEs with rates ≥5% and with a ≥2% difference between Paliperidone ER and risperidone were identified. Completion rates for placebo-treated subjects in Paliperidone ER trials (n = 95) and risperidone trials (n = 122) groups were 36.8% and 51.6%, respectively; end point changes on PANSS total scores were similar (p = 0.768). Completion rates for subjects receiving Paliperidone ER 6-12 mg/day (n = 179), risperidone 2-4 mg/day (n = 113) or risperidone 4-6 mg/day (n = 129) were 64.8%, 54.0% and 66.7%, respectively (placebo-adjusted rates: Paliperidone ER vs risperidone 2-4 mg/day, p = 0.005; Paliperidone ER vs risperidone 4-6 mg/day, p = 0.159). PANSS total score improvement with Paliperidone ER was greater than with risperidone 2-4 mg/day (difference in mean change score, -6.7; p < 0.05) and similar to risperidone 4-6 mg/day (0.2; p = 0.927). Placebo-adjusted AEs more common with Paliperidone ER were insomnia, sinus tachycardia and tachycardia; more common with risperidone were somnolence, restlessness, nausea, anxiety, salivary hypersecretion, akathisia, dizziness and nasal congestion. Weight changes with Paliperidone ER and risperidone were similar (Paliperidone ER vs risperidone 2-4 mg/day, p = 0.489; Paliperidone ER vs risperidone 4-6 mg/day, p = 0.236). This indirect database analysis suggested that Paliperidone ER 6-12 mg/day may be more efficacious than risperidone 2-4 mg/day and as efficacious as risperidone 4-6 mg/day. The AE-adjusted incidence rates suggest differences between treatments that may be relevant for individual patients. Additional randomized, direct, head-to-head clinical trials are needed to confirm these findings.
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randomized double blind placebo controlled study of Paliperidone extended release and quetiapine in inpatients with recently exacerbated schizophrenia
American Journal of Psychiatry, 2009Co-Authors: Carla M Canuso, Cynthia A Bossie, Bryan Dirks, Jennifer Carothers, Colette Kosikgonzalez, Young Zhu, C V Damaraju, Amir H Kalali, Ramy A MahmoudAbstract:Objective: The authors compared Paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization. Method: In a 6-week double-blind study, inpatients with a recent exacerbation of schizophrenia were randomly assigned to treatment with Paliperidone extended-release, quetiapine, or placebo. A 2-week monotherapy phase was followed by a 4-week additive-therapy phase. Target doses were at the upper end of recommended ranges: Paliperidone extended-release, 9 or 12 mg/day, and quetiapine, 600 or 800 mg/day. The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale (PANSS) between Paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint. Results: Six-week completion rates were 77.5% (124/160) with Paliperidone extended-release, 66.7% (106/159) quetiapine, and 63.8% (51/80) placebo. Improvement in mean PANSS total change score was greater with Paliperidone extended-release than...
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Paliperidone extended release tablets in schizophrenia patients previously treated with risperidone
International Clinical Psychopharmacology, 2008Co-Authors: Carla M Canuso, Ibrahim Turkoz, Cynthia A Bossie, Eriene Youssef, A Schreiner, George M SimpsonAbstract:To assess the effect of Paliperidone extended-release (ER) tablets in patients with acute symptoms who had previously received risperidone. Data for this post-hoc analysis were pooled from three 6-week, double-blind, placebo-controlled trials in patients treated with Paliperidone ER 3-12 mg/day or placebo. Patients had to have received risperidone for ≥ 4 weeks within 2 weeks of study entry. Assessments were done using the Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity scale, Personal and Social Performance scale, the Simpson-Angus Scale, and adverse event (AE) reports. Altogether, 198 patients (Paliperidone ER, n=142; placebo, n=56) met the established criteria. Mean (SD) duration of prior risperidone treatment and dose were 418.8 (572.8) days and 4.4 (2.5) mg/day for Paliperidone ER and 527.0 (805.3) days and 4.1 (2.5) mg/day for placebo. Study completion rates were 61.3% for Paliperidone ER versus 42.9% for placebo. At endpoint, Paliperidone ER showed significant improvement versus placebo (P<0.05) in Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity, and Personal and Social Performance scores. Mean baseline Simpson-Angus Scale scores were low, with no significant changes at endpoint in either group. AEs 2≥10% with Paliperidone ER versus placebo were headache (16.2 vs.16.1%), insomnia (14.1 vs. 16.1%), and agitation (8.5 vs. 10.7%). AE-related discontinuations were 2.1 % with Paliperidone ER and 5.4% with placebo. In patients who had received risperidone previously but remained sufficiently symptomatic for enrollment, Paliperidone ER was significantly more effective than placebo in reducing symptoms and producing functional gains.
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Paliperidone extended-release tablets in schizophrenia patients previously treated with risperidone.
International clinical psychopharmacology, 2008Co-Authors: Carla M Canuso, Ibrahim Turkoz, Cynthia A Bossie, Eriene Youssef, A Schreiner, George M SimpsonAbstract:To assess the effect of Paliperidone extended-release (ER) tablets in patients with acute symptoms who had previously received risperidone. Data for this post-hoc analysis were pooled from three 6-week, double-blind, placebo-controlled trials in patients treated with Paliperidone ER 3-12 mg/day or placebo. Patients had to have received risperidone for ≥ 4 weeks within 2 weeks of study entry. Assessments were done using the Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity scale, Personal and Social Performance scale, the Simpson-Angus Scale, and adverse event (AE) reports. Altogether, 198 patients (Paliperidone ER, n=142; placebo, n=56) met the established criteria. Mean (SD) duration of prior risperidone treatment and dose were 418.8 (572.8) days and 4.4 (2.5) mg/day for Paliperidone ER and 527.0 (805.3) days and 4.1 (2.5) mg/day for placebo. Study completion rates were 61.3% for Paliperidone ER versus 42.9% for placebo. At endpoint, Paliperidone ER showed significant improvement versus placebo (P
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does half life matter after antipsychotic discontinuation a relapse comparison in schizophrenia with 3 different formulations of Paliperidone
The Journal of Clinical Psychiatry, 2017Co-Authors: Peter J Weiden, Ibrahim Turkoz, Srihari Gopal, Edward Kim, Jason Bermak, Joris BerwaertsAbstract:OBJECTIVE To evaluate the effect of 1 oral and 2 distinct long-acting injectable (LAI) formulations of the same antipsychotic on times to relapse following medication discontinuation. METHODS Data were drawn from 3 similarly designed, multicenter, double-blind, placebo-controlled, randomized-withdrawal studies of Paliperidone in adults with a schizophrenia diagnosis (according to DSM-IV criteria for ≥ 1 year before screening): once-daily extended-release oral Paliperidone (ORAL Paliperidone), once-monthly Paliperidone palmitate (PP1M), and once-every-3-months Paliperidone palmitate (PP3M). In a post hoc analysis, we compared median time to relapse across the treatment-withdrawal arms of the 3 studies using final analysis datasets. Time to relapse in the withdrawal arm of each study was examined using log-rank tests and Cox proportional hazards models. RESULTS Four hundred forty-nine patients were withdrawn from 3 Paliperidone formulations: 101 from ORAL Paliperidone, 203 from PP1M, and 145 from PP3M. Postwithdrawal median (95% confidence interval [CI]) days to relapse were 58 days (42-114 days) for ORAL Paliperidone, 172 days (134-222 days) for PP1M, and 395 days (274 days-not reached) for PP3M (P < .0001, pairwise comparisons). Relapse risk was significantly lower (P < .001) for patients who withdrew from either PP formulation relative to ORAL Paliperidone and additionally for patients who withdrew from PP3M relative to PP1M. CONCLUSIONS Results demonstrate that 50% of patients who withdrew treatment from ORAL Paliperidone, PP1M, or PP3M remained relapse free for approximately 2 months, 6 months, and 13 months, respectively. This may be relevant for risk mitigation strategies in schizophrenia, a condition in which interruptions in maintenance antipsychotic treatment are commonplace and unpredictable. LAI antipsychotic formulations may provide substantial delays over oral equivalents in times to relapse when patients discontinue therapy. TRIAL REGISTRATION ClinicalTrials.gov identifiers: NCT00086320, NCT00111189, and NCT01529515.
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drug drug interaction studies of Paliperidone and divalproex sodium extended release tablets in healthy participants and patients with psychiatric disorders
The Journal of Clinical Pharmacology, 2016Co-Authors: Bart Remmerie, Marc De Meulder, Jay Ariyawansa, Danielle Coppola, Joris BerwaertsAbstract:The objective of these 2 phase 1, open-label, 2-treatment, single-sequence studies was to evaluate the effect of repeated oral doses of divalproex sodium extended-release (ER) on the pharmacokinetics (PK) of a single dose of Paliperidone ER in healthy participants (study 1), and the effect of multiple doses of Paliperidone ER on the steady-state PK of valproic acid (VPA) in patients with psychiatric disorders (study 2), respectively. In study 1 healthy participants received, in a fixed sequential order, treatment A, Paliperidone ER 12 mg (day 1); treatment B, VPA 1000 mg (2 × 500 mg divalproex sodium ER) once daily (days 5 to 18) and Paliperidone ER 12 mg (day 15). In study 2 patients received treatment A, VPA (days 1-7); treatment B, VPA + Paliperidone ER 12 mg (days 8-12). Divalproex sodium ER doses (study 2) were individualized such that systemic therapeutic VPA exposure from prior treatment was maintained on entry into the study. PK assessments were performed at prespecified time points (Paliperidone days 1 and 15 [study 1]; VPA days 7 and 12 [study 2]). The oral bioavailability of Paliperidone was increased by an estimated 51% (Cmax ) and 51%-52% (AUCs) when coadministered with divalproex sodium ER. No effect on the steady-state plasma concentration of VPA was observed following repeated coadministration with Paliperidone ER: the 90%CI around the VPA exposure ratios for the 2 treatments was within the 80%-125% bioequivalence criteria for Cmax,ss and AUCτ . Both VPA and Paliperidone ER were well tolerated, and no new safety concerns were identified.
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efficacy and safety of the 3 month formulation of Paliperidone palmitate vs placebo for relapse prevention of schizophrenia a randomized clinical trial
JAMA Psychiatry, 2015Co-Authors: Joris Berwaerts, Bart Remmerie, Isaac Nuamah, Srihari Gopal, Danielle Coppola, Yanning Liu, Adam Savitz, Alain Schotte, Nataliya Maruta, David HoughAbstract:Importance Treatment nonadherence and relapse are common problems in patients with schizophrenia. The long-acting 3-month formulation of Paliperidone palmitate, owing to its extended elimination half-life, may offer a valuable therapeutic option for these patients. Objective To evaluate the efficacy and safety of the 3-month formulation of Paliperidone palmitate vs placebo in delaying time to relapse of schizophrenia symptoms. Design, Setting, and Participants This randomized, multicenter trial conducted from April 26, 2012, through April 9, 2014, in 8 countries consisted of 4 phases: 3-week screening phase, flexible-dose 17-week open-label transition phase, 12-week open-label maintenance phase, and open-ended double-blind (DB) phase. Of the 506 patients enrolled (aged 18-70 years; DSM-IV-TR diagnosis of schizophrenia), 305 were randomized to 3-month Paliperidone palmitate (n = 160) or placebo (n = 145) in the DB phase. Interventions Patients received once-monthly doses of the 1-month formulation of Paliperidone palmitate (50, 75, 100, or 150 mg eq) during the transition phase, followed by a single dose of the 3-month formulation (3.5 times the stabilized dose of once-monthly Paliperidone palmitate) during the maintenance phase. Stabilized patients were randomized to receive either a fixed dose of 3-month Paliperidone palmitate (175, 263, 350, or 525 mg eq) or placebo once every 3 months during the DB phase. Main Outcomes and Measures Time from randomization to the first relapse event (time to relapse) in the DB phase. Results In the interim analysis, time to first relapse was significantly different in favor of the Paliperidone palmitate group vs the placebo group (hazard ratio = 3.45; 95% CI, 1.73-6.88; P Conclusions and Relevance Compared with placebo, the 3-month formulation of Paliperidone palmitate administered 4 times yearly significantly delayed time to relapse in patients with schizophrenia. The 3-month formulation was generally tolerable and has a safety profile consistent with other marketed Paliperidone formulations. Trial Registration clinicaltrials.gov Identifier:NCT01529515
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a randomized placebo and active controlled study of Paliperidone extended release as maintenance treatment in patients with bipolar i disorder after an acute manic or mixed episode
Journal of Affective Disorders, 2012Co-Authors: Joris Berwaerts, Isaac Nuamah, Rama Melkote, Pilar LimAbstract:Abstract Background Paliperidone ER monotherapy was efficacious in treating acute mania in two 3-week studies in patients with bipolar I disorder. We assessed its efficacy in a study investigating maintenance treatment of clinically stable patients with this disorder. Methods Patients (n = 766), aged 18 to 65 years inclusive, with current manic or mixed episodes were initially randomized (4:1) to flexibly-dosed Paliperidone ER (3–12 mg/day) or olanzapine (5–20 mg/day; 3-week acute treatment phase); responders continued the same treatment (12-week continuation phase). Patients on Paliperidone ER who achieved remission during this phase were randomized (1:1) to fixed-dose Paliperidone ER (n = 152) or placebo (n = 148); those on olanzapine continued to receive that at fixed dose (n = 83) (maintenance phase). Results Median time to recurrence of any mood symptoms (primary endpoint) was: 558 days (Paliperidone ER), 283 days (placebo) and not observed with olanzapine ( Limitations Responder-enriched design prevents extrapolation of data to patients not previously stabilized on Paliperidone ER. Conclusions Paliperidone ER significantly delayed the time to recurrence of any mood symptoms, versus placebo, in patients with bipolar I disorder. No new safety concerns emerged.
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Number needed to treat and number needed to harm with Paliperidone palmitate relative to long-acting haloperidol, bromperidol, and fluphenazine decanoate for treatment of patients with schizophrenia
Dove Medical Press, 2011Co-Authors: Srihari Gopal, Joris Berwaerts, Isaac NuamahAbstract:Srihari Gopal1, Joris Berwaerts1, Isaac Nuamah1, Kasem Akhras2, Danielle Coppola1, Ella Daly1, David Hough1, Joseph Palumbo11Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, NJ, USA; 2Johnson & Johnson Pharmaceutical Services, LLC, Raritan, NJ, USABackground: We analyzed data retrieved through a PubMed search of randomized, placebo-controlled trials of first-generation antipsychotic long-acting injectables (haloperidol decanoate, bromperidol decanoate, and fluphenazine decanoate), and a company database of Paliperidone palmitate, to compare the benefit-risk ratio in patients with schizophrenia.Methods: From the eight studies that met our selection criteria, two efficacy and six safety parameters were selected for calculation of number needed to treat (NNT), number needed to harm (NNH), and the likelihood of being helped or harmed (LHH) using comparisons of active drug relative to placebo. NNTs for prevention of relapse ranged from 2 to 5 for Paliperidone palmitate, haloperidol decanoate, and fluphenazine decanoate, indicating a moderate to large effect size.Results: Among the selected maintenance studies, NNH varied considerably, but indicated a lower likelihood of encountering extrapyramidal side effects, such as akathisia, tremor, and tardive dyskinesia, with Paliperidone palmitate versus placebo than with first-generation antipsychotic depot agents versus placebo. This was further supported by an overall higher NNH for Paliperidone palmitate versus placebo with respect to anticholinergic use and Abnormal Involuntary Movement Scale positive score. LHH for preventing relapse versus use of anticholinergics was 15 for Paliperidone palmitate and 3 for fluphenazine decanoate, favoring Paliperidone palmitate.Conclusion: Overall, Paliperidone palmitate had a similar NNT and a more favorable NNH compared with the first-generation long-acting injectables assessed.Keywords: long-acting injectables, first-generation antipsychotics, randomized, number needed to treat, number needed to harm, Paliperidone palmitate, second-generation antipsychotic