Topical Glycopyrronium Tosylate for the Treatment of Primary Axillary Hyperhidrosis: Patient-Reported Outcomes from the ATMOS-1 and ATMOS-2 Phase III Randomized Controlled Trials

Abstract

Background: Glycopyrronium tosylate (GT) is a topical anticholinergic approved in the USA for primary axillary hyperhidrosis in patients aged ≥ 9 years. GT was evaluated for primary axillary hyperhidrosis in replicate, randomized, double-blind, vehicle-controlled, phase III trials. GT reduced sweating severity and production versus vehicle and was generally well tolerated.

Objective: Our objective was to evaluate patient-reported outcomes (PROs) from these trials.

Methods: Patients aged ≥ 9 years with primary axillary hyperhidrosis ≥ 6 months, gravimetrically measured sweat production ≥ 50 mg/5 min in each axilla, Axillary Sweating Daily Diary (ASDD) Item 2 severity score ≥ 4, and Hyperhidrosis Disease Severity Scale (HDSS) score ≥ 3 were randomized 2:1 to GT 3.75% or vehicle applied once daily to each axilla for 4 weeks. The 4-item ASDD, 6 Weekly Impact (WI) items, Patient Global Impression of Change (PGIC), HDSS, and Dermatology Life Quality Index (DLQI) were utilized.

Results: In the pooled population, 463 patients were randomized to GT and 234 to vehicle; 426 (92.0%) and 225 (96.2%) completed the trials. At baseline, most patients considered their axillary sweating to be at least moderate in severity, impact, and bothersomeness (ASDD items 2, 3, and 4, respectively). Improvement was substantially greater for GT than for vehicle at every study week, and, at week 4, ASDD scores improved from baseline by 62.6 versus 34.0% (severity), 65.5 versus 40.3% (impact), and 65.4 versus 39.0% (bothersomeness). Improvements favoring GT versus vehicle also occurred for WI items, PGIC, HDSS, and DLQI.

Conclusions: PRO results demonstrated that GT reduced the disease burden of primary axillary hyperhidrosis.

Trial registration: Clinicaltrials.gov; ATMOS-1 (NCT02530281), ATMOS-2 (NCT02530294).

Conflict of interest statement

Ethical Approval/Informed Consent

ATMOS-1 was conducted in the USA and Germany; ATMOS-2 was conducted in the USA. Trial protocols and informed consent forms were approved by local institutional review boards or independent ethics committees on 13 May 2015, and the first patients were enrolled in July 2015 (ATMOS-1) and August 2015 (ATMOS-2). The trials were registered on ClinicalTrials.gov on 21 August 2015 (ATMOS-1 [NCT02530281] and ATMOS-2 [NCT02530294]). Both trials were carried out in accordance with Good Clinical Practice and the Declaration of Helsinki.

Conflicts of Interest

DMP has received honoraria for consultancy from Brickell Biotech, Inc., Biofrontera AG, Celgene, Dermira, Inc., DUSA Pharmaceuticals, Inc., LEO Pharma, Novartis, Promius Pharma, LLC, Regeneron Pharmaceuticals, Inc., Sanofi, TheraVida, Inc., and Valeant Pharmaceuticals International, Inc; honoraria for participating on an advisory board for Pfizer, Inc.; investigator grants/research funding from Abbott Laboratories; Amgen, Inc.; Brickell Biotech, Inc.; Celgene; Dermavant Sciences; Eli Lilly and Company; LEO Pharma; Merck & Co, Inc.; Novartis; Novo Nordisk A/S; Ortho Dermatologics; Peplin, Inc.; Photocure ASA; Promius Pharma, LLC; Regeneron Pharmaceuticals, Inc.; Stiefel Laboratories; and Valeant Pharmaceuticals International, Inc.; and investigator honoraria from LEO Pharma and Pfizer, Inc. AAH has received investigator research funding from Dermira, Inc. (paid to the UTHealth McGovern Medical School, Houston); advisory board honoraria from Dermira, Inc.; research funding (all monies paid to the UTHealth McGovern Medical School) from Allergan, Plc., Amgen, Inc., Cassiopea, Celgene, Dermavant Sciences, Eli Lilly and Company, Galderma S.A., GSK, Plc., LEO Pharma, Mayne Pharma, Medimetriks Pharmaceuticals, Novan, Inc., Promius Pharma, LLC, and Vanda Pharmaceuticals; honoraria from Amgen, GSK, Plc., Pfizer, Inc., and Valeant Pharmaceutics International, Inc. JD and RG are employees of Dermira, Inc. JQ is a consultant for Dermira, Inc. and an employee of QST Consultations. DAG is a consultant and investigator for Dermira, Inc. and an investigator for Allergan, ATACAMA, Brickell, Galderma, Revance, and Sienna.

Figures

Fig. 1

Axillary sweating weekly impact at baseline and week 4 (pooled population). GT glycopyrronium tosylate

Fig. 2

Improvement from baseline on patient-reported outcome measures (pooled population). ASDD Axillary Sweating Daily Diary, ASDD-C children’s version of the ASDD (two items), GT glycopyrronium tosylate

Fig. 3

Patient Global Impression of Change at week 4 (pooled population). No patients in either the ATMOS-1 or the ATMOS-2 trial rated their change as “moderately worse” (score = 6) or “much worse” (score = 7); therefore, these categories were combined with the category of “a little worse” (score  = 5). p value for the comparison of GT vs. vehicle was derived from an ANCOVA with factors of treatment group and analysis center. ANCOVA analysis of covariance, GT glycopyrronium tosylate

Fig. 4

Improvement from baseline to week 4 in DLQI and CDLQI (pooled population). CfB values are mean ± standard deviation. **p < 0.01 for GT vs. vehicle at week 4 from an ANCOVA with factors of treatment group and analysis center and a covariate of baseline score. ANCOVA analysis of covariance, CDLQI children’s Dermatology Life Quality Index, CfB change from baseline, CDLQI children’s Dermatology Life Quality Index, DLQI Dermatology Life Quality Index, GT glycopyrronium tosylate