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

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.

Hyperhidrosis Quality of Life Index (HidroQoL©): further validation and clinical application in patients with axillary hyperhidrosis using data from a phase III randomized controlled trial.

BACKGROUND: The Hyperhidrosis Quality of Life Index (HidroQoL©) is a validated patient-reported outcome measure capturing the quality of life of people affected by hyperhidrosis. OBJECTIVES: We aimed to extend the validity evidence to physician-confirmed diagnosis of primary axillary hyperhidrosis. METHODS: Data from a phase III randomized placebo-controlled clinical trial were used (n = 171). Confirmatory factor analysis was carried out to confirm the a priori two-factor structure of the HidroQoL. Internal consistency was assessed using Cronbach's α. Intraclass correlation coefficients (ICCs) were calculated to evaluate test-retest reliability after days -7 to -4. Convergent validity was assessed using correlations with the Dermatology Life Quality Index (DLQI), the Hyperhidrosis Disease Severity Scale (HDSS) and gravimetric sweat production. Known groups were analysed to evaluate discriminative validity. Responsiveness after 29 days was assessed and minimal important difference (MID) values were calculated using both anchor- and distribution-based approaches. All analyses were carried out for total HidroQoL and its two domains. RESULTS: The two-factor structure of the HidroQoL was confirmed. Internal consistency and test-retest reliability were strong (Cronbach's α 0·81-0·90; ICCs 0·89-0·93). Correlations with other outcome measures were in line with a priori hypotheses. The HidroQoL discriminated between different severity groups (P ≤ 0·001) and showed sensitivity to change towards improvement (P < 0·001). An MID value of 4 is proposed for the total scale. CONCLUSIONS: This study supports excellent measurement properties including clinical applicability of the HidroQoL in primary axillary hyperhidrosis and suggests a MID of 4 be applied to clinical trial data.

Efficacy and safety of non-hormonal remedies for vaginal dryness: open, prospective, randomized trial.

OBJECTIVES: To prove non-inferiority of the first non-hormonal vaginal cream in Germany, Vagisan(®) Moisturising Cream (CREAM), compared to a non-hormonal vaginal gel (GEL) for vulvovaginal atrophy (VVA) symptom relief. METHOD: This was a 12-week multicenter, open-label, prospective, randomized, two-period, cross-over phase-III trial. The primary endpoint was the cumulative VVA subjective symptom score of the respective treatment period. Secondary endpoints were assessment of single VVA subjective and objective symptoms, VVA objective symptom score, vaginal pH, safety parameters, overall assessment of efficacy, tolerability and evaluation of product properties. In total, 117 women were randomly allocated to either one of the two treatments, each administered for 4 weeks; 92 women were included in the per-protocol analysis (primary analysis). The main outcome measure was cumulative VVA subjective symptom score. RESULTS: Regarding VVA symptom relief, results confirmed non-inferiority of CREAM compared to GEL and even indicated superiority of CREAM. Frequency and intensity of subjective symptoms and objective findings were clearly reduced, with CREAM showing better results compared to GEL. Mean VVA objective symptom score significantly decreased; improvement was significantly greater with CREAM. Vaginal pH decreased only following CREAM treatment. Tolerability was superior for CREAM: burning and itching, mostly rated as mild, occurred markedly less often with CREAM than with GEL. Overall satisfaction with treatment efficacy, tolerability and most product properties were rated significantly superior for CREAM. CONCLUSIONS: Subjective and objective VVA symptoms were reliably and safely reduced by both non-hormonal topical products. However, efficacy and tolerability of CREAM were shown to be superior to GEL.