Safety, pharmacokinetics, and preliminary pharmacodynamics of 1% and 3% diclofenac vaginal hydrogel for the treatment of primary dysmenorrhea: a randomized, placebo controlled trial.

This article focuses on a Phase 1 randomized, double-blind, placebo-controlled clinical trial evaluating the safety and pharmacokinetics (PK) of a novel 1% and 3% diclofenac vaginal hydrogel (DARE-PDM1) in healthy premenopausal women with symptomatic primary dysmenorrhea. The study found that both concentrations were well tolerated, with no significant differences in treatment emergent adverse events compared to placebo, and systemic diclofenac exposure was substantially lower than oral dosing. Vaginal fluid concentrations of diclofenac were markedly higher than plasma levels, supporting localized drug delivery. Preliminary exploratory efficacy data suggested non-significant reductions in dysmenorrhea-associated pain scores, though the study was not powered for efficacy outcomes and baseline pain scores varied between groups. These findings support further development of vaginal diclofenac hydrogel as a potential alternative to oral NSAIDs for primary dysmenorrhea to reduce systemic side effects.