A glycopyrronium bromide 1% cream for topical treatment of primary axillary hyperhidrosis: efficacy and safety results from a phase IIIa randomized controlled trial*

Abstract

Summary Background Effective topical treatment options for patients with primary axillary hyperhidrosis (PAHH) are limited. A phase I trial showed promising results regarding the efficacy and safety of a topical cream containing glycopyrronium bromide (GPB). Objectives To assess the efficacy, safety and tolerability of a 4‐week topical treatment of GPB 1% cream in patients with PAHH vs. placebo. Methods In total, 171 patients (84 receiving placebo; 87 receiving GPB 1%) with PAHH were included in the 4‐week, multicentre, randomized, double‐blind, placebo‐controlled phase IIIa part of the pivotal study. Sweat production was measured by gravimetry. Patients rated the impact of disease with the Hyperhidrosis Disease Severity Scale (HDSS) and Hyperhidrosis Quality of Life Index (HidroQoL©). Results Absolute change in sweat production from baseline to day 29 in logarithmic values was significantly larger in the GPB 1% group compared with the placebo group (P = 0·004). The improvement in HidroQoL exceeded the minimal clinically important difference of 4. The proportion of responders was twofold higher for sweat reduction (–197·08 mg GPB 1% vs. –83·49 mg placebo), HDSS (23% GPB 1% vs. 12% placebo) and HidroQoL (60% GPB 1% vs. 26% placebo). Treatment was safe: most treatment‐emergent adverse effects were mild or moderate, and transient. Local tolerability was very good, with 9% of patients having only mild or moderate application‐site reactions. The most reported adverse drug reaction was dry mouth (16%), an expected anticholinergic effect of the treatment. Conclusions GPB 1% cream may provide an effective new treatment option exhibiting a good safety profile for patients with PAHH. The long‐term open‐label part (phase IIIb) is ongoing.

Topical anticholinergic medications for primary hyperhidrosis: A protocol for a systematic review and meta-analysis

“…Topical Sofpironium bromide(ECCLOCK®, 5%) gel reduces sweat secretion by inhibiting local sweat gland M3 muscarinic receptor [37] , approved in Japan in September 2020. In addition, topical preparation of GPB has aroused interest as a treatment option for PHH [38] , and 1% GPB cream has completed the phase IIIa study [39] . A dermal preparation of Umeclidinium (UMEC) ammonium bromide is also under way [40] .…”

Pharmacokinetic profile data of glycopyrronium bromide 1% cream beyond 2 weeks are important

“…In 2021, Pariser et al reported the pharmacokinetic (PK) profile of GP tosylate wipes applied by patients with hyperhidrosis for 4 weeks with a 2-week off-drug follow-up. 4 In view of the likely systemic absorption of topical anticholinergic agents, the possible risks of their long-term use and the potential interindividual variability, especially in elderly patients, we believe that data on the PK profile of the GPB 1% cream formulation for a time period beyond 2 weeks are of great importance in real-world practice and need to be considered and critically evaluated in an appropriately extended clinical trial programme. DEAR EDITOR, Gregoriou et al have asked for systemic pharmacokinetic (PK) data beyond 2 weeks after the topical application of glycopyrronium (GP) bromide (GPB)-containing cream for treatment of primary axillary hyperhidrosis, 1 compared to another recently approved GP tosylate (GPT)-containing topical product.…”

“…Dear Editor , Abels et al . have reported the results of a phase IIIa randomized placebo‐controlled study assessing the efficacy and safety of a formulation of glycopyrronium (GP) bromide (GPB) 1% cream applied for 4 weeks as a topical treatment for primary axillary hyperhidrosis 1 . In the preceding phase Ib trial, three concentrations of GPB cream were applied topically for 2 weeks: 0·5%, 1% and 2%.…”

Pharmacokinetic profile data of glycopyrronium bromide 1% cream beyond 2 weeks are important: reply from the authors

“…The PK data (C max ) of GP are predictive of anticholinergic adverse events (AEs) following topical application regarding frequency and severity. 2 As the frequency of systemic, anticholinergic AEs was lower after treatment with GPB cream than with GPT-containing wipes, 3,4 plasma concentrations after topical application of GPB cream are unlikely to exceed those of GPT-containing wipes.…”

“…This is not surprising, as 1% cream contains only 0Á8% GP vs. 2Á4% GP in wipes. Local tolerability was clearly worse after the application of the alcoholic wipes, 3,4 indicating impairment of the epidermal barrier and contributing to an increased permeation of GPT.…”