P15.09
Background: The Dapivirine Vaginal Ring-004 (25 mg dapivirine) is a topical microbicide currently being evaluated in Phase III trials. Given the potential for interactions with co-administered vaginal products, pharmacokinetic assessments were performed during co-use of Ring-004 and the antifungal miconazole nitrate.
Methods: An open-label, randomised, crossover trial was conducted among 36 healthy, HIV-negative women, aged 18–40 years. Participants used dapivirine Ring-004 for 28 days, alone or together with a single dose of miconazole nitrate (1200 mg vaginal capsule). A single dose of miconazole nitrate was administered alone in a third treatment period. Washout periods of 3 weeks were included between treatments. Dapivirine and miconazole concentrations were determined in plasma and vaginal fluid (CVF) samples, and residual dapivirine levels were assessed in used rings.
Results: A single vaginal dose of miconazole nitrate at the time of dapivirine ring insertion increased the systemic exposure (Cmax and AUC) of dapivirine by approximately 20%, but decreased dapivirine CVF levels up to 14 days post-ring insertion (decreases of 26% in Cmax and 69% in AUC0–24h). No significant difference was observed between dapivirine ring residual levels with and without concomitant miconazole, suggesting similar dapivirine release. Dapivirine CVF levels remained at least 100 times higher than the in vitro IC99 in cervical tissue (3.3 ng/mL). Local and systemic miconazole exposure was increased after co-administration with Ring-004 (1.4 to 6-fold higher). Concomitant use of the two products was safe and well tolerated. One product-unrelated SAE occurred (acetabulum fracture); one Grade 2 event of vulvovaginal candidiasis (ring alone) was considered product-related.
Conclusions: Concomitant use of Ring-004 and a single vaginal dose of miconazole nitrate altered the local and systemic levels of both drugs, but these changes are considered unlikely to affect adversely the efficacy of either drug.
