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Janicem Smiell - One of the best experts on this subject based on the ideXlab platform.
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A meta-analytic approach to an integrated summary of efficacy: a case study of Becaplermin gel.
Controlled clinical trials, 2002Co-Authors: Barbara H Perry, Allan R Sampson, Barry H. Schwab, M.rezaul Karim, Janicem SmiellAbstract:This paper presents a case study involving a meta-analytic approach for an integrated summary of efficacy based upon four phase II and III clinical trials that comprised the basis for a Biologics License Application to the U.S. Food and Drug Administration for approval of Becaplermin gel. There were substantial variations in observed response rates across the four studies that were of concern to regulatory agencies. Due to these variations and because there were various treatment combinations in the four trials, standard statistical methods for an integrated analysis of efficacy were problematic. A meta-analytic model that focused on the variations of concern was employed to permit a suitable integrated analysis. The resulting integrated analysis clarified response rate variability and provided accurate estimates of treatment effects based upon the four clinical trials. While this meta-analysis was viewed by neither regulators nor the sponsor as a confirmatory analysis, it was seen by both regulators and sponsor as strongly supportive of the efficacy of Becaplermin gel.
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recombinant human platelet derived growth factor bb Becaplermin for healing chronic lower extremity diabetic ulcers an open label clinical evaluation of efficacy
Wound Repair and Regeneration, 2000Co-Authors: John M Embil, Janicem Smiell, Kim Papp, Gary Sibbald, Jacqueline Tousignant, Betty Wong, Cathy Y LauAbstract:Topically applied recombinant human platelet-derived growth factor-BB (Becaplermin) is a new pharmacologically active therapy for chronic, neuropathic, lower extremity diabetic ulcers. In previous studies, Becaplermin gel was administered once daily but dressings were changed twice daily. In the present study of 134 patients with diabetes mellitus and full thickness lower extremity ulcers, dressings were changed only once per day, simplifying the treatment regimen. Efficacy criteria included the percentage of patients achieving complete healing within the 20-week treatment period, the time to achieve complete healing, the rate of ulcer recurrence during the 6-month period following healing, and treatment compliance. Complete healing of ulcers was achieved in 57. 5% of patients, with a mean time to closure of 63 days and a recurrence rate of 21% at 6 months. Of the potential factors affecting ulcer healing, only drug compliance (p < 0.001), dressing compliance (p < 0.01), the presence of infection (p < 0.01), baseline ulcer area (p < 0.05), and baseline total wound evaluation score (p < 0.05) were significantly associated with healing. Results of this study further confirm the efficacy and safety of Becaplermin gel for the treatment of lower extremity diabetic ulcers.
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efficacy and safety of Becaplermin recombinant human platelet derived growth factor bb in patients with nonhealing lower extremity diabetic ulcers a combined analysis of four randomized studies
Wound Repair and Regeneration, 1999Co-Authors: Janicem Smiell, Barbara H Perry, Jeffery T Wieman, David L Steed, Allan R Sampson, Barry SchwabAbstract:The results of a combined analysis and separate analyses of four multicenter, randomized, parallel group studies that evaluated the effects of once-daily topical administration of Becaplermin gel for the treatment of chronic, full thickness, lower extremity diabetic ulcers are presented. The four studies included a total of 922 patients with nonhealing lower extremity diabetic ulcers of at least 8 weeks' duration. Following initial complete sharp debridement of the ulcer, patients were randomized to receive a standardized regimen of good ulcer care alone, good ulcer care plus placebo gel, or good ulcer care plus Becaplermin gel-30 microg/g, or good ulcer care plus Becaplermin gel-100 microg/g, with various combinations of regimens used in the four studies. Safety was assessed by monitoring adverse events and by clinical laboratory evaluations. Meta-analytic statistical techniques were used in the combined analysis to establish homogeneity of treatment comparisons across studies. Based on an analysis of patients with baseline ulcer area common to all trials (Becaplermin gel-100 microg/g significantly increased (p = 0.007) the probability of complete healing compared with placebo gel. It was determined that for the median ulcer area of these patients, which was 1.5 cm2, the Becaplermin gel-100 microg/g treatment group showed a 39% increase in complete healing compared with that of the placebo gel treatment group (50% vs. 36%, respectively, p = 0.007). Becaplermin gel-100 microg/g significantly decreased (p = 0.01) the time to complete healing compared with placebo gel, with the 35th percentile of time to complete healing being reduced by 30% (14.1 weeks vs. 20. 1 weeks, respectively). In patients with ulcers Becaplermin gel-100 microg/g also significantly increased the incidence of complete healing with a similar decrease in the time to healing. Adverse events reported during treatment or during a 3-month follow-up period were not unexpected for this patient population and were similar in nature and incidence across all treatment groups. We therefore conclude that treatment with Becaplermin gel at a dose of 100 microg/g once daily, in conjunction with good ulcer care, is effective and well tolerated in patients with full thickness lower extremity diabetic ulcers.
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Becaplermin gel in the treatment of pressure ulcers a phase ii randomized double blind placebo controlled study
Wound Repair and Regeneration, 1999Co-Authors: Riley S Rees, Janicem Smiell, Martin C Robson, Barbara H PerryAbstract:Pressure ulcers are associated with significant rates of morbidity and mortality, particularly in the geriatric and spinal cord‐injured populations. Newer pharmacologically active therapies include the use of topically applied recombinant human platelet-derived growth factor-BB (Becaplermin), the active ingredient in REGRANEX ® (Becaplermin) Gel 0.01%, which has been approved in the United States for treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. In this study, the efficacy of Becaplermin gel in the treatment of chronic full thickness pressure ulcers was compared with that of placebo gel. A total of 124 adults (♢ 18 years of age) with pressure ulcers were assigned randomly to receive topical treatment with Becaplermin gel 100 μg/g (n = 31) or 300 μg/g (n = 32) once daily alternated with placebo gel every 12 hours, Becaplermin gel 100 μg/g twice daily (n = 30), or placebo (sodium carboxymethylcellulose) gel (n = 31) twice daily until complete healing was achieved or for 16 weeks. All treatment groups received a standardized regimen of good wound care throughout the study period. Study endpoints were the incidence of complete healing, the incidence of ♢ 90% healing, and the relative ulcer volume at endpoint (endpoint/baseline). Once-daily treatment of chronic pressure ulcers with Becaplermin gel 100 μg/g or 300 μg/g significantly increased the incidences of complete and ♢ 90% healing and significantly reduced the median relative ulcer volume at endpoint compared with that of placebo gel (p < 0.025 for all comparisons). Becaplermin gel 300 μg/g did not result in a significantly greater incidence of healing than that observed with 100 μg/g. Treatment with Becaplermin gel was generally well tolerated and the incidence of adverse events was similar among treatment groups. In conclusion, once-daily application of Becaplermin gel is efficacious in the treatment of chronic full thickness pressure ulcers. (WOUND REP REG 1999;7:141‐147) Pressure ulcers are a prevalent clinical problem. Conservative estimates indicate that in the United States alone, over 2 million people in hospitals and nursing
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Efficacy and safety of Becaplermin (recombinant human platelet‐derived growth factor‐BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 1999Co-Authors: Janicem Smiell, T. Jeffery Wieman, Barbara H Perry, David L Steed, Allan R Sampson, Barry H. SchwabAbstract:The results of a combined analysis and separate analyses of four multicenter, randomized, parallel group studies that evaluated the effects of once-daily topical administration of Becaplermin gel for the treatment of chronic, full thickness, lower extremity diabetic ulcers are presented. The four studies included a total of 922 patients with nonhealing lower extremity diabetic ulcers of at least 8 weeks' duration. Following initial complete sharp debridement of the ulcer, patients were randomized to receive a standardized regimen of good ulcer care alone, good ulcer care plus placebo gel, or good ulcer care plus Becaplermin gel-30 microg/g, or good ulcer care plus Becaplermin gel-100 microg/g, with various combinations of regimens used in the four studies. Safety was assessed by monitoring adverse events and by clinical laboratory evaluations. Meta-analytic statistical techniques were used in the combined analysis to establish homogeneity of treatment comparisons across studies. Based on an analysis of patients with baseline ulcer area common to all trials (
Denise W Metry - One of the best experts on this subject based on the ideXlab platform.
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response of ulcerated perineal hemangiomas of infancy to Becaplermin gel a recombinant human platelet derived growth factor
Archives of Dermatology, 2004Co-Authors: Brandie J Metz, Melissa C Rubenstein, Moise L Levy, Denise W MetryAbstract:Background Hemangiomas of infancy are the most common tumors of childhood , and ulceration is the most common complication. Many treatments have been usedfor hemangioma ulceration, although none are uniformly effective. A recent report described the successful use of 0.01% Becaplermin gel, a recombinanthuman platelet-derived growth factor, for an ulcerated hemangioma refractory to standard care. We sought to further assess the responsiveness of hemangiomaulceration to 0.01% Becaplermin gel and to compare its cost to that of conventional modalities. Observations We report a case series of 8 infants treated with Becaplermin gel for ulcerated perineal hemangiomas of infancy. All infants were seen between Januaryand June 2003 in the pediatric dermatology clinic at Texas Children's Hospital.Six female and 2 male infants were included. All of the hemangiomas were large(≥6 cm 2 ), and of superficial or mixed superficial and deep morphology. Rapid ulcer healing occurred in all patients within 3 to 21 days (average,10.25 days). Conclusions In this small series, 0.01% Becaplermin gel was a safe and effective treatment for perineal hemangioma ulceration. The rapid healing achieved with0.01% Becaplermin gel allows a reduction in the risk of secondary infection, pain, and need for hospitalization, as well as in the costs that often accumulatefrom multiple follow-up visits and long-term therapy.
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Update on hemangiomas of infancy.
Current opinion in pediatrics, 2004Co-Authors: Denise W MetryAbstract:PURPOSE OF REVIEW: Recent clinical and basic science research has led to advances in the understanding of hemangiomas of infancy. RECENT FINDINGS: New developments include (1) the establishment of a relation between hemangiomas of infancy and placental tissue, (2) the discovery of unique immunohistochemical markers for hemangiomas of infancy, (3) the importance of morphology and location in determining potential risk for underlying complications, and (4) the discovery of Becaplermin 1% gel as an effective therapy for refractory ulceration. SUMMARY: The morphology and location of a hemangioma of infancy are critically important factors in determining potential risk for complications. Ongoing research is bringing closer an understanding of the cause of hemangioma, which will provide opportunities for the development of interventional, and ultimately preventative, therapies.
Dennis D. Gagnon - One of the best experts on this subject based on the ideXlab platform.
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Development and validation of the Diabetic Foot Ulcer Scale-Short Form (DFS-SF)
PharmacoEconomics, 2003Co-Authors: Carla M. Bann, Sheri E. Fehnel, Dennis D. GagnonAbstract:Background: The Diabetic Foot Ulcer Scale (DFS) provides comprehensive measurement of the impact of diabetic foot ulcers on patients’ QOL through self-administration of 64 items comprising 15 subscales. Objective: To develop and evaluate a short form of the DFS (DFS-SF) to reduce patient burden and the number of outcome measures, and to improve sensitivity to change in clinical condition. Methods: The DFS-SF was created through the analysis of data from a doubleblind, placebo-controlled, randomised trial of the efficacy and safety of Becaplermin (recombinant human platelet-derived growth factor BB) in the treatment of chronic, full-thickness, neuropathic, diabetic foot ulcers. Using these data, items demonstrating poor psychometric properties were eliminated. Exploratory factor analyses were then conducted to develop a new, more parsimonious scaling algorithm that optimised the internal consistency of the new subscales. Finally, data from two additional clinical trials were used to assess replicability of the DFS-SF subscale structure. Results: The DFS-SF contains a total of 29 items comprising six subscales. The results of both confirmatory and exploratory factor analyses provided support for the scaling algorithm. The DFS-SF subscales showed good internal consistency, reliability and construct validity, and demonstrated sensitivity to ulcer healing. Conclusions: The results of this investigation indicate that the DFS-SF has good psychometric properties and replicability.
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Development and Validation of the Diabetic Foot Ulcer Scale-Short Form (DFS-SF)
1Co-Authors: Carla M. Bann, Sheri E. Fehnel, Dennis D. GagnonAbstract:Background: The Diabetic Foot Ulcer Scale (DFS) provides comprehensive measurement of the impact of diabetic foot ulcers on patients Objective: To develop and evaluate a short form of the DFS (DFS-SF) to reduce patient burden and the number of outcome measures, and to improve sensitivity to change in clinical condition. Methods: The DFS-SF was created through the analysis of data from a double- blind, placebo-controlled, randomised trial of the efficacy and safety of Becaplermin (recombinant human platelet-derived growth factor BB) in the treatment of chronic, full-thickness, neuropathic, diabetic foot ulcers. Using these data, items demonstrating poor psychometric properties were eliminated. Exploratory factor analyses were then conducted to develop a new, more parsimonious scaling algorithm that optimised the internal consistency of the new subscales. Finally, data from two additional clinical trials were used to assess replicability of the DFS-SF subscale structure. Results: The DFS-SF contains a total of 29 items comprising six subscales. The results of both confirmatory and exploratory factor analyses provided support for the scaling algorithm. The DFS-SF subscales showed good internal consistency, reliability and construct validity, and demonstrated sensitivity to ulcer healing. Conclusions: The results of this investigation indicate that the DFS-SF has good psychometric properties and replicability.Diabetic-foot-ulcer, Quality-of-life-rating-scales
Jeffrey I Jones - One of the best experts on this subject based on the ideXlab platform.
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Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor That Accelerates Healing.
Journal of medicinal chemistry, 2018Co-Authors: Trung T. Nguyen, Derong Ding, William R. Wolter, Rocio L Pérez, Matthew M. Champion, Kiran V. Mahasenan, Dusan Hesek, Mijoon Lee, Valerie A. Schroeder, Jeffrey I JonesAbstract:Diabetic foot ulcers (DFUs) are a significant health problem. A single existing FDA-approved drug for this ailment, Becaplermin, is not standard-of-care. We previously demonstrated that upregulation of active matrix metalloproteinase (MMP)-9 is the reason that the diabetic wound in mice is recalcitrant to healing and that MMP-8 participates in wound repair. In the present study, we validate the target MMP-9 by identifying and quantifying active MMP-8 and MMP-9 in human diabetic wounds using an affinity resin that binds exclusively to the active forms of MMPs coupled with proteomics. Furthermore, we synthesize and evaluate enantiomerically pure ( R)- and ( S)-ND-336, as inhibitors of the detrimental MMP-9, and show that the ( R)-enantiomer has superior efficacy in wound healing over Becaplermin. Our results reveal that the mechanisms of pathology and repair are similar in diabetic mice and diabetic humans and that ( R)-ND-336 holds promise for the treatment of DFUs as a first-in-class therapeutic.
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Validation of Matrix Metalloproteinase‑9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP‑9 Inhibitor That Accelerates Healing
2018Co-Authors: Trung T. Nguyen, Derong Ding, William R. Wolter, Matthew M. Champion, Kiran V. Mahasenan, Dusan Hesek, Mijoon Lee, Valerie A. Schroeder, Rocio L. Pérez, Jeffrey I JonesAbstract:Diabetic foot ulcers (DFUs) are a significant health problem. A single existing FDA-approved drug for this ailment, Becaplermin, is not standard-of-care. We previously demonstrated that upregulation of active matrix metalloproteinase (MMP)-9 is the reason that the diabetic wound in mice is recalcitrant to healing and that MMP-8 participates in wound repair. In the present study, we validate the target MMP-9 by identifying and quantifying active MMP-8 and MMP-9 in human diabetic wounds using an affinity resin that binds exclusively to the active forms of MMPs coupled with proteomics. Furthermore, we synthesize and evaluate enantiomerically pure (R)- and (S)-ND-336, as inhibitors of the detrimental MMP-9, and show that the (R)-enantiomer has superior efficacy in wound healing over Becaplermin. Our results reveal that the mechanisms of pathology and repair are similar in diabetic mice and diabetic humans and that (R)-ND-336 holds promise for the treatment of DFUs as a first-in-class therapeutic
Carla M. Bann - One of the best experts on this subject based on the ideXlab platform.
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Development and validation of the Diabetic Foot Ulcer Scale-Short Form (DFS-SF)
PharmacoEconomics, 2003Co-Authors: Carla M. Bann, Sheri E. Fehnel, Dennis D. GagnonAbstract:Background: The Diabetic Foot Ulcer Scale (DFS) provides comprehensive measurement of the impact of diabetic foot ulcers on patients’ QOL through self-administration of 64 items comprising 15 subscales. Objective: To develop and evaluate a short form of the DFS (DFS-SF) to reduce patient burden and the number of outcome measures, and to improve sensitivity to change in clinical condition. Methods: The DFS-SF was created through the analysis of data from a doubleblind, placebo-controlled, randomised trial of the efficacy and safety of Becaplermin (recombinant human platelet-derived growth factor BB) in the treatment of chronic, full-thickness, neuropathic, diabetic foot ulcers. Using these data, items demonstrating poor psychometric properties were eliminated. Exploratory factor analyses were then conducted to develop a new, more parsimonious scaling algorithm that optimised the internal consistency of the new subscales. Finally, data from two additional clinical trials were used to assess replicability of the DFS-SF subscale structure. Results: The DFS-SF contains a total of 29 items comprising six subscales. The results of both confirmatory and exploratory factor analyses provided support for the scaling algorithm. The DFS-SF subscales showed good internal consistency, reliability and construct validity, and demonstrated sensitivity to ulcer healing. Conclusions: The results of this investigation indicate that the DFS-SF has good psychometric properties and replicability.
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Development and Validation of the Diabetic Foot Ulcer Scale-Short Form (DFS-SF)
1Co-Authors: Carla M. Bann, Sheri E. Fehnel, Dennis D. GagnonAbstract:Background: The Diabetic Foot Ulcer Scale (DFS) provides comprehensive measurement of the impact of diabetic foot ulcers on patients Objective: To develop and evaluate a short form of the DFS (DFS-SF) to reduce patient burden and the number of outcome measures, and to improve sensitivity to change in clinical condition. Methods: The DFS-SF was created through the analysis of data from a double- blind, placebo-controlled, randomised trial of the efficacy and safety of Becaplermin (recombinant human platelet-derived growth factor BB) in the treatment of chronic, full-thickness, neuropathic, diabetic foot ulcers. Using these data, items demonstrating poor psychometric properties were eliminated. Exploratory factor analyses were then conducted to develop a new, more parsimonious scaling algorithm that optimised the internal consistency of the new subscales. Finally, data from two additional clinical trials were used to assess replicability of the DFS-SF subscale structure. Results: The DFS-SF contains a total of 29 items comprising six subscales. The results of both confirmatory and exploratory factor analyses provided support for the scaling algorithm. The DFS-SF subscales showed good internal consistency, reliability and construct validity, and demonstrated sensitivity to ulcer healing. Conclusions: The results of this investigation indicate that the DFS-SF has good psychometric properties and replicability.Diabetic-foot-ulcer, Quality-of-life-rating-scales