A 44-Week Open-Label Study Evaluating Safety and Efficacy of Topical Glycopyrronium Tosylate in Patients with Primary Axillary Hyperhidrosis

Abstract

Background: Glycopyrronium tosylate is a topical anticholinergic approved in the USA for primary axillary hyperhidrosis in patients aged ≥ 9 years (Qbrexza™ [glycopyrronium] cloth, 2.4%).

Objective: This 44-week open-label extension study assessed glycopyrronium tosylate safety and descriptive efficacy in patients completing one of two, phase III, double-blind, vehicle-controlled, 4-week trials (NCT02530281; NCT02530294).

Methods: Patients aged ≥ 9 years with primary axillary hyperhidrosis were randomized 2:1 (glycopyrronium tosylate: vehicle, once daily) in the double-blind trials. Completers could receive open-label glycopyrronium tosylate for up to an additional 44 weeks. Treatment-emergent adverse events and local skin reactions were assessed. Descriptive efficacy assessments were gravimetrically measured sweat production, Hyperhidrosis Disease Severity Scale responder rate (≥ 2 grade improvement), and Dermatology Life Quality Index/children's Dermatology Life Quality Index.

Results: Of 651 patients completing the double-blind trials, 564 (86.6%) entered the open-label extension; 550 were analyzed. Most patients experiencing treatment-emergent adverse events had mild or moderate events (> 90%). Discontinuation because of treatment-emergent adverse events remained low and relatively stable, with a cumulative rate of 8.0% (44/550) over 44 weeks. Common treatment-emergent adverse events (> 5%) were dry mouth (16.9%), vision blurred (6.7%), application-site pain (6.4%), nasopharyngitis (5.8%), and mydriasis (5.3%). Most patients (67.5%) had no local skin reactions; those occurring were predominantly mild/moderate. Glycopyrronium tosylate efficacy was maintained throughout the trial; at week 44, the Hyperhidrosis Disease Severity Scale responder rate was 63.2%, and improvements from baseline (double blind) in sweat production were - 71.3% and 8.7 ± 6.2/6.2 ± 4.9 for Dermatology Life Quality Index/children's Dermatology Life Quality Index.

Conclusions: Daily long-term application of glycopyrronium tosylate for up to 48 weeks (double blind plus open label) was generally well tolerated and efficacy was maintained. No new safety signals emerged.

Trial registry: Clinicaltrials.gov NCT02553798.

Conflict of interest statement

Dee Anna Glaser is an investigator for Allergan, Galderma, ATACAMA, Brickell Biotech, Inc., Dermira, Inc., Evolus, and Sienna Biopharmaceuticals, Inc. and a consultant for Dermira, Inc. William P. Werschler is a consultant and investigator for Dermira, Inc. Adelaide A. Herbert is a consultant for Dermira, Inc. and an employee of the UTHealth McGovern Medical School, which received compensation from Dermira, Inc. for study participation. Alexander Nast is an employee of Charité – Universitätsmedizin Berlin, which received compensation from Dermira, Inc. for study participation; he was an advisory board member for Boehringer Ingelheim, carried out educational activities for Bayer and Novartis, and received research grants from Eli Lilly and Company, Pfizer, GSK, Plc., and MEDA. Lawrence Green is an investigator for Brickell Biotech, Inc. and an advisory board member and investigator for Dermira, Inc. Richard D. Mamelok is a consultant for Dermira, Inc. John Quiring is an employee of QST Consultations. Janice Drew is an employee of Dermira, Inc. David M. Pariser is a consultant and investigator for Brickell Biotech, Inc., Celgene Corporation, Dermira, Inc., LEO Pharma US, Novartis Pharmaceuticals, Promius Pharmaceuticals, Regeneron, and Valeant Pharmaceuticals International, a consultant for ATACAMA, Biofrontera AG, DUSA Pharmaceuticals, Inc., Sonofi, TDM SurgiTech, Inc., and TheraVida, and an investigator for Abbott Laboratories, Amgen, Asana Biosciences, Dermavant Sciences, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Ortho Dermatologics, Peplin Inc., Pfizer Inc., Photocure ASA, and Stiefel (as GSK company).

Figures

Fig. 1

Patient disposition. a651 of 697 patients (93.4%) randomized to treatment in ATMOS-1 and ATMOS-2 completed the ATMOS studies. bSponsor terminated the study early, per protocol, when the study objective of 100 patients receiving treatment for at least 12 months was achieved. GT glycopyrronium tosylate

Fig. 2

Local skin reactions (LSRs) in the open-label trial to week 44/end of treatment/early termination (ET) [n = 550]. The safety population includes patients receiving one or more doses of glycopyrronium tosylate (GT) and having one or more post-baseline assessments in the open-label extension. Patients were counted as having an LSR if any post-baseline assessment was mild, moderate, or severe; percentages represent the proportion of patients who had LSR events with a maximum post-baseline severity of mild, moderate, or severe

Fig. 3

Sweat production: change from baseline (week 0 of double-blind trials) for (a) all glycopyrronium tosylate (GT)-treated patients and (b) analysis by double-blind treatment assignment. aSweat production values reported were gravimetrically measured averages from the left and right axillae. bBaseline in the double-blind ATMOS-1/ATMOS-2 trials for GT-treated patients only. cPooled ATMOS-1/ATMOS-2 intent-to-treat (ITT) population (all randomized patients dispensed the study drug in ATMOS-1/ATMOS-2); missing data were imputed by Markov chain Monte Carlo. dBaseline in the double-blind ATMOS-1/ATMOS-2 trials for vehicle (VEH)- and GT-treated patients who continued into the open-label extension and received GT treatment thereafter. eOpen-label safety population (patients receiving one or more doses of GT and having one or more post-baseline assessments in the open-label extension); the pre-specified analysis of week 44/end of treatment/early termination (ET) included patients who completed 44 weeks of open-label GT and patients who terminated the study early; there was no imputation for missing data. fData are for week 4 of the double-blind ATMOS-1/ATMOS-2 trials for those patients entering the open-label extension. CfB change from baseline, GT → GT patients assigned to GT in the double-blind trials who continued taking GT in the open-label extension, VEH → GT patients assigned to VEH in the double-blind trials who were newly exposed to GT in the open-label extension

Fig. 4

Hyperhidrosis Disease Severity Scale (HDSS) improvement from baseline (week 0 of double-blind trials) for (a) proportion of glycopyrronium tosylate (GT)-treated patients with 0-, 1-, 2-, or 3-grade HDSS improvement from baseline to week 4 of double-blind trials and week 44/end of treatment/early termination (ET) of the open-label extension trial, (b) HDSS responder rate (≥ 2-grade improvement from baseline) in the open-label trial to week 44/ET, and (c) analysis by double-blind treatment assignment: HDSS responder rate to week 44. The open-label safety population includes patients receiving one or more doses of GT and having one or more post-baseline assessments in the open-label extension. The pre-specified analysis of week 44/ET included patients who completed 44 weeks of open-label GT and patients who terminated the study early; there was no imputation for missing data. GT → GT patients assigned to GT in the double-blind trials who continued on GT in the open-label extension, VEH vehicle, VEH → GT patients assigned to VEH in the double-blind trials who were newly exposed to GT in the open-label extension

Fig. 5

Dermatology Life Quality Index (DLQI) and children’s DLQI (CDLQI) mean scores for (a) change from baseline (week 0 of double-blind trials) in DLQIa, (b) change from baseline (week 0 of double-blind trials) in CDLQIf, and (c) analysis by double-blind treatment assignment: change in DLQI. aPatients > 16 years of age. bBaseline in ATMOS-1/ATMOS-2 for glycopyrronium tosylate (GT)-treated patients only. cATMOS-1/ATMOS-2 intent-to-treat population (all randomized patients dispensed the study drug in ATMOS-1/ATMOS-2). dBaseline in ATMOS-1/ATMOS-2 for vehicle (VEH)- and GT-treated patients who continued into ARIDO and received GT treatment thereafter. eOpen-label safety population (patients receiving one or more doses of GT and having one or more post-baseline assessments in the open-label extension); the pre-specified analysis of week 44/end of treatment/early termination (ET) included patients who completed 44 weeks of open-label GT and patients who terminated the study early; there was no imputation of missing data. fPatients ≤ 16 years of age. CfB change from baseline, GT → GT patients assigned to GT in the double-blind trials who continued on GT in the open-label extension, VEH → GT patients assigned to VEH in the double-blind trials who were newly exposed to GT in the open-label extension