Limited Systemic Exposure with Topical Glycopyrronium Tosylate in Primary Axillary Hyperhidrosis

Abstract

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

Objective: The objective of this study was to compare the pharmacokinetics and safety of GT to oral glycopyrrolate (phase I study) and assess the relationship between glycopyrronium pharmacokinetics and anticholinergic-related adverse events or efficacy with population pharmacokinetics using data from two phase II studies.

Methods: In the phase I study, study staff applied GT to axillae of patients with primary axillary hyperhidrosis (aged 9-65 years) once daily (5 days); oral glycopyrrolate was administered to healthy adults (aged 18-65 years) every 8 hours (15 days). In the phase II studies (NCT02016885 [20 December, 2013], NCT02129660 [2 May, 2014]), adults with primary axillary hyperhidrosis applied topical glycopyrronium (0.8-3.2%) or vehicle to axillae once daily (4 weeks). Pharmacokinetic and adverse event data were collected in all studies.

Results: Glycopyrronium pharmacokinetic parameters were similar between adult and pediatric patients treated with GT; there was no evidence of accumulation. Systemic absorption of glycopyrronium was lower with GT vs oral glycopyrrolate. No anticholinergic-related adverse events occurred with GT in the phase I study, while dry mouth and nasal dryness occurred with oral glycopyrrolate; anticholinergic adverse events occurred in the phase II studies. In the population pharmacokinetic analysis, frequency/severity of anticholinergic-related adverse events increased with higher glycopyrronium concentration; no relationship was observed between efficacy and pharmacokinetic measures.

Conclusions: These studies indicate limited absorption of GT compared to oral glycopyrrolate and a low risk of anticholinergic adverse events with proper GT administration when following instructions for use (wipe each underarm once with same cloth, wash hands, avoid ocular contact).

Conflict of interest statement

David M. Pariser was an investigator and consultant for Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company, and received writing assistance. Edward L. Lain has received payment from the sponsor for work as a principal investigator, advisory board member, speaker, and consultant, but did not receive compensation for work related to the preparation and publication of this article. Richard D. Mamelok is a paid consultant to Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company, and received financial support for reviewing data and for reviewing the manuscript. Janice Drew is a full-time employee and receives a salary from the sponsor of the study, Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company. Diane R. Mould is the president of Projections Research Inc., a consulting company for the pharmaceutical industry and was a paid consultant of Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company for the conduct of the data analysis.

Figures

Fig. 1

Phase I study design. Study staff administered all the study drug. Topical glycopyrronium tosylate (GT; 2.4%) was applied to each axilla once daily. Because of the oral glycopyrrolate titration schedule (1.0 mg/8 h, then increased by 1.0-mg increments every 5 days to a maximum of 3.0 mg/8 h if no dose-limiting side effects), the oral glycopyrrolate arm was 17 days long whereas the GT arm, which did not involve titration, was 7 days long. Pediatric patients (included only in the GT arm; age 9 to

Fig. 2

Population pharmacokinetic study: probability of anticholinergic adverse events (frequency). Shading denotes the 95% confidence interval; patients randomized to vehicle were assigned a value of “0” for glycopyrronium exposure. CI confidence interval, Cmax maximum plasma concentration

Fig. 3

Population pharmacokinetic study: probability of anticholinergic adverse events (severity). Shading denotes the 95% confidence interval. CI confidence interval, Cmax maximum plasma concentration