Randomized, Placebo- and Active-Controlled Crossover Study of the Safety and Efficacy of THVD-102, a Fixed-dose Combination of Oxybutynin and Pilocarpine, in Subjects With Primary Focal Hyperhidrosis.

BACKGROUND: While muscarinic antagonists (anticholinergics) have shown efficacy in treating primary focal hyperhidrosis (PFH), side effects - most commonly dry mouth - are intolerable for most patients. THVD-102, a fixed-dose combination product has been developed combining oxybutynin, a muscarinic antagonist, and pilocarpine, a muscarinic agonist. The pilocarpine is at a dose level and release profile optimized to correct salivary flow impaired by oxybutynin yet not interfere with the therapeutic muscarinic antagonist effect of oxybutynin upon the sweat glands. OBJECTIVES: This study evaluated safety, efficacy, dry mouth and quality of life with THVD-102 (oxybutynin 7.5 mg / pilocarpine 7.5 mg) in subjects with axillary and / or palmar PFH. METHODS: After a 21-day open label treatment period with oxybutynin 5 mg twice daily to determine susceptibility of subjects to develop dry mouth, eligible subjects were randomized to 1 of 6 sequences of 3 study treatments (THVD-102, oxybutynin 7.5 mg, and placebo) in sequential 21day double-blind crossover treatment periods, each preceded by a washout period of at least 7 days. RESULTS: A total of 24 subjects were randomized and 19 finished all crossover treatments. Changes from baseline to end of treatment in symptoms associated with PFH were statistically significant for both THVD-102 versus placebo and for oxybutynin versus placebo as assessed by multiple measures. Beneficial trends, not statistically significant, for gravimetric measurements were also observed. There were no statistically significant differences between THVD-102 and oxybutynin in PFH efficacy. Fewer subjects reported moderate to severe dry mouth while receiving THVD-102 compared to oxybutynin and more subjects categorized their dry mouth as none or mild while receiving THVD-102 compared to oxybutynin. Differences in reported dry mouth were statistically significant. CONCLUSION: THVD-102 was generally well-tolerated. Both THVD-102 and oxybutynin 7.5 mg twice daily were effective in treating PFH. THVD-102 was associated with significantly reduced dry mouth compared to oxybutynin. J Drugs Dermatol. 2017;16(2):127-132..