Long-term efficacy and safety of topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: Post hoc pediatric subgroup analysis from a 44-week open-label extension study

Abstract

Background/objectives: Glycopyrronium tosylate (GT) cloth, 2.4% is a topical anticholinergic approved in the United States for primary axillary hyperhidrosis in patients ≥9 years. This post hoc analysis evaluated long-term response (efficacy and safety) in pediatric patients (≥9 to ≤16 years) to GT in the 44-week, open-label extension (NCT02553798) of two, phase 3, double-blind, vehicle-controlled, 4-week trials (NCT02530281, NCT02530294).

Methods: In the double-blind trials, patients ≥9 years with primary axillary hyperhidrosis were randomized 2:1 to once-daily GT:vehicle. Those who completed the study could receive open-label GT for up to an additional 44 weeks. Safety assessments included treatment-emergent adverse events (TEAEs) and local skin reactions (LSRs). Descriptive efficacy assessments included gravimetrically measured sweat production, Hyperhidrosis Disease Severity Scale response (≥2-grade improvement), and Children's Dermatology Life Quality Index.

Results: Of 43 pediatric patients completing either double-blind trial, 38 (88.4%) entered the open-label extension (age, years: 9 [n = 1], 12 [n = 2], 13 [n = 7], 14 and 15 [n = 9 each], 16 [n = 10]). The safety profile observed was similar to the double-blind trials. Most TEAEs (>95%) were mild/moderate, related to anticholinergic activity, and infrequently led to discontinuation (n = 1/38 [2.6%]). No pediatric patients experienced a serious TEAE. Most anticholinergic TEAEs did not require a dose modification and resolved within 7 days. Approximately, one-third of patients (n = 13/38 [34.2%]) had LSRs; most were mild/moderate in severity. Improvements in efficacy measures were maintained from the double-blind trials.

Conclusions: Long-term, once-daily GT for up to 48 weeks (4-week double-blind plus 44 week open label) provides a noninvasive, well-tolerated treatment option for pediatric patients with primary axillary hyperhidrosis.

Keywords: anticholinergic; axilla; glycopyrronium tosylate; hyperhidrosis; sweat.

Conflict of interest statement

Dr Hebert is a consultant for Dermira, Inc. and an employee of the UTHealth McGovern Medical School, Houston, which received compensation from Dermira, Inc. for study participation. Dr Hebert has also been an investigator for Brickell Biotech, Inc. All research funds are paid to the medical school. Dr Glaser is a consultant for Dermira, Inc., and an investigator for Allergan, Atacama Therapeutics, Brickell Biotech, Inc., Galderma, and Revance Therapeutics, Inc. She has received honoraria for consulting with Allergan and Dermira, Inc. Dr Green is an investigator for Brickell Biotech, Inc., and a consultant, investigator, and speaker for Dermira, Inc. Dr Hull is an investigator for Northwestern Arkansas Clinical Trials Center which receives compensation from Dermira, Inc. for study participation. Dr Cather is an investigator and advisory board member who has received honoraria from AbbVie, Inc., Celgene Corporation, Eli Lilly and Company, and Regeneron Pharmaceuticals, Inc. She is an investigator for Dermira, Inc. Ms Drew and Dr Gopalan are employees of Dermira, Inc. Dr Pariser received honoraria for consulting for Atacama Therapeutics, Brickell Biotech, Inc., Biofrontera AG, Celgene Corporation, Dermira, Inc., DUSA Pharmaceuticals, Inc., LEO Pharma, Inc., Novartis Pharmaceuticals Corporation, Promius Pharma, LLC, Regeneron Pharmaceuticals, Inc., Sanofi, TDM SurgiTech, Inc., TheraVida, Inc., and Valeant Pharmaceuticals International, Inc. He received honoraria for advisory board participation for Pfizer, Inc. He received grants/research funding for serving as an investigator for Abbott Laboratories, Amgen, Inc., Asana BioSciences, LLC, Brickell Biotech, Inc., Celgene Corporation, Dermavant Sciences, Inc., Eli Lilly and Company, LEO Pharma, Inc., Merck & Company, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ortho Dermatologics, Inc., Peplin, Inc., Photocure ASA, Promius Pharma, LLC, Regeneron Pharmaceuticals, Inc., Stiefel Laboratories, and Valeant Pharmaceuticals International, Inc. He received honoraria for serving as an investigator for LEO Pharma, Inc. and Pfizer, Inc.

© 2020 The Authors. Pediatric Dermatology published by Wiley Periodicals, Inc.

Figures

Figure 1

Sweat productiona improvement: Grav‐50 responder rate (≥50% reduction in sweat production from Baselineb) at Week 4 of the double‐blind trials9 and Week 44 or ETc of the OLE. aGravimetrically measured average from the left and right axillae. bBaseline for the OLE is Baseline of the double‐blind trials for vehicle‐treated and GT‐treated patients who continued into the OLE and received GT treatment thereafter. cET refers to Week 44 for patients who completed the OLE and end of treatment for those who did not. dAge of pediatric patients in 1‐y increments at Week 44 or ET: 9 y, 12 y: n = 1 each; 13 y: n = 4; 14 y, 15 y, 16 y: n = 8 each. P‐values were not calculated for this post hoc analysis. In the double‐blind trials, multiple imputation (MCMC) was used to impute missing values; no imputation of missing values was performed in the OLE. ET, end of treatment; GT, glycopyrronium tosylate; ITT, intent‐to‐treat; MCMC, Markov chain Monte Carlo; OLE, open‐label extension; y, years

Figure 2

HDSS responder rate (≥2‐grade improvement from Baseline): Week 0 of the double‐blind trials9 (GT‐treated patients only) to Week 44a,b of the OLE (for all patients who continued into the OLE and received GT treatment thereafter). aWeek 44 data include observed cases at Week 44 (n = 21). bMost patients discontinued due to the protocol‐required study termination (study objective met). cAge of pediatric patients in 1‐year increments at Week 44: 13 y: n = 4; 14 y: n = 5, 15 y: n = 5, 16 y: n = 7. P‐values were not calculated for this post hoc analysis. Baseline for the OLE is the Baseline of the double‐blind trials for vehicle‐treated and GT‐treated patients who continued into the OLE and received GT treatment thereafter. In the double‐blind trials, multiple imputation (MCMC) was used to impute missing values; no imputation of missing values was performed in the OLE. GT, glycopyrronium tosylate; HDSS, Hyperhidrosis Disease Severity Scale; ITT, intent‐to‐treat; MCMC, Markov chain Monte Carlo; OLE, open‐label extension; y, years

Figure 3

Mean CDLQI scores at Baseline (Week 0 of double‐blind trials) and Week 4 of the double‐blind trials,9 Week 20 and 44 or ETa of the OLE. aET refers to Week 44 for patients who completed the OLE and end of treatment for those who did not. bAge of pediatric patients in 1‐year increments at Week 20:12 y: n = 1; 13 y, 14 y: n = 7 each; 15 y: n = 8; 16y: n = 5. cAge of pediatric patients in 1‐y increments at Week 44 or ET: 9 y, 12y: n = 1 each; 13y: n = 4; 14y: n = 8; 15 y: n = 7; 16 y: n = 5. The CDLQI questionnaire is validated for use in patients ≥4 to ≤16 y.16P‐values were not calculated for this post hoc analysis. Baseline for the OLE is the Baseline of the double‐blind trials for vehicle‐treated and GT‐treated patients who continued into the OLE and received GT treatment thereafter. No imputation of missing values in the double‐blind trials or OLE. CDLQI, children's Dermatology Life Quality Index; ET, end of treatment; GT, glycopyrronium tosylate; ITT, intent‐to‐treat; OLE, open‐label extension; y, years