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

Abstract

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.

Figure 1

CONSORT flow diagram for the phase IIIa trial. ^aOne patient missed the day 15 visit but returned for day 29. ^b‘Other reasons’ indicated no or not enough effect of treatment. EC, exclusion criterion; EOS, end of study; FU, follow‐up; GPB, glycopyrronium bromide; IC, inclusion criterion.

Figure 2

(a) Absolute sweat production (mg) in 5 min as measured by gravimetry at baseline and day 29. Data are shown for the full analysis set (n = 171). Boxes represent the lower and upper quartile; median values are indicated by the horizontal lines, mean values by a ‘+’, and upper and lower whiskers indicate the maximum and minimum values (excluding outliers). Outliers are shown as grey rectangles (placebo) or red circles [glycopyrronium bromide (GPB) 1%]. (b) Change in sweat production from baseline to day 29. Data are shown as mean (SD) for the full analysis set (n = 171: 84 in the placebo group and 87 in the GBP 1% group). *Statistically significant (P‐value for treatment effect is based on the mixed model using the absolute change in logarithmic values of sweat production).