MTN-030/IPM 041

Primary Objectives

• To characterize the local and systemic pharmacokinetics of a DPV vaginal ring formulation and a DPV-LNG vaginal ring formulation used continuously for 14 days
• To evaluate the safety of a DPV vaginal ring formulation and a DPV-LNG vaginal ring formulation used continuously for 14 days

Study Summary
MTN-030/IPM 041 was a multi-site, randomized (1:1), double blind Phase 1 trial. The study assessed pharmacokinetics and safety of two silicone elastomer vaginal matrix rings containing either 200 mg of dapivirine alone or 200 mg of dapivirine and 320 mg of levonorgestrel. The study population consisted of healthy, HIV-uninfected, non-pregnant women between 18-45 years of age. Twenty-four participants were randomized to use one of the two vaginal rings for a period of approximately 14 days and were followed up for a total duration of approximately 16 days. The primary objectives of MTN-030/IPM 041 was to collect pharmacokinetic and safety data on rings containing either dapivirine alone or a combination of dapivirine and levonorgestrel, formulated with higher dapivirine dose strengths than previously evaluated in Phase 3 trials. The effects of the study product had on vaginal bleeding patterns was also examined. MTN-030/IPM 041 also assessed the acceptability of and adherence to this dual-purpose product and evaluated the vaginal microenvironment (microflora and biomarkers) during 14 days of continuous study product use. MTN-030/IPM 041 was the first in human study of a vaginal ring containing a combination of dapivirine and levonorgestrel.

MTN-030/IPM 041 completed follow-up August 18, 2017. Results were presented at the HIV Research for Prevention (HIVR4P) meeting held on October 22-25, 2018, in Madrid, Spain. Primary and secondary manuscripts are in development.

Primary Results
Of the 24 enrolled participants, 23 were evaluable. Both formulations were well-tolerated and no safety concerns were identified. A total of 43 AEs were reported (36 Grade 1 and 7 Grade 2). The number of women with related Grade 2 genitourinary AEs in the dapivirine vs dapivirine/ levonorgestrel arms was not significantly different (2/11 (18%) vs 0/12 (0%), p=0.2). No Grade 3 or higher AEs were reported. All participants reported full adherence to within 15-min over 14-days. Median plasma dapivirine C_max trended higher in dapivirine/ levonorgestrel arm compared to the dapivirine arm (661 vs 499 pg/mL, respectively, p=0.05). Median vaginal fluid dapivirine C_max was not significantly different between dapivirine/levonorgestrel and dapivirine users (183 vs 107 ng/mL, respectively, p=0.09). The median plasma dapivirine t1/2 was 50h (IQR 37-52h) for the dapivirine/ levonorgestrel ring. Median plasma levonorgestrel C_max was 1.6 ng/mL (IQR 1.1-2.6). These reported local and systemic dapivirine and levonorgestrel concentrations support further evaluation of this vaginal ring.