Pharmacokinetics, safety and preliminary pharmacodynamic evaluation of DARE-VVA1: a soft gelatin capsule containing tamoxifen for the treatment of vulvovaginal atrophy.

This study aimed to measure safety, systemic pharmacokinetics and preliminary efficacy of a vaginal tamoxifen capsule (DARE-VVA1) among postmenopausal women with moderate-to-severe vulvovaginal atrophy. This was a randomized, placebo-controlled, double-blind, phase 1/2 study of DARE-VVA1, in four doses (1, 5, 10 and 20 mg). Seventeen women were enrolled and 14 completed the 8-week treatment. DARE-VVA1 was safe. All adverse events were of mild or moderate severity and distributed similarly among active and placebo groups. Plasma tamoxifen concentrations were highest among women using DARE-VVA1 20 mg, but the maximum mean (standard deviation) plasma tamoxifen concentrations on day 1 (2.66 ± 0.85 ng/ml) and day 56 (5.69 ± 1.87 ng/ml) were <14% of those measured after one oral tamoxifen dose. Active study product users had significant decreases from pre-treatment baseline in vaginal pH and proportion of vaginal parabasal cells ( DARE-VVA1 is safe and results in minimal systemic exposure to tamoxifen. Preliminary efficacy data support further development of this product.