154. Pharmacokinetics and Safety of GS-1720 Following Multiple Ascending Doses in a Phase 1a Study in People Without HIV-1

作者：Haeyoung Zhang, Ines Mendes, Eva Mortensen, Hui Wang, Aaron Share, Monika Sobczyk, Ramesh Palaparthy, Dhananjay Marathe · 发表于：Open Forum Infectious Diseases · 年份：2025 · DOI：10.1093/ofid/ofae631.040 · 研究领域：HIV/AIDS drug development and treatment、Drug Transport and Resistance Mechanisms、HIV-related health complications and treatments

Abstract Background Long-acting antiretrovirals for HIV-1 treatment may improve adherence by reducing treatment fatigue. GS-1720 is an oral integrase strand transfer inhibitor (INSTI) with potent anti-HIV-1 activity. Pharmacokinetics (PK) and safety of single ascending GS-1720 doses in participants without HIV-1 have been previously reported. Here, we report preliminary PK and safety of multiple ascending doses (MAD). Methods In this Phase 1a, randomized, blinded, placebo-controlled, multicohort study, oral GS-1720 or placebo (6:3/cohort) was administered under fasting conditions in 3 once-weekly (QW) and 2 once-daily (QD) MAD cohorts. Participants received 150, 450, or 1350 mg of GS-1720, or placebo, for 6 weeks or 450 or 900 mg of GS-1720, or placebo, for 7 or 14 days, respectively. Primary endpoints were plasma PK parameters (including AUC, Cmax, and accumulation ratios) and incidence of adverse events (AEs) and laboratory abnormalities. Participants were followed up to Day (D) 105. Results Overall, 45 participants were enrolled: median age, 29–40 years; 47% female. For QW doses of 150, 450, or 1350 mg at Week 6, respectively, mean (coefficient of variation [CV]%) Cmax was 19.9 (21.3), 39.6 (23.3), and 60.6 (25.8) μg/mL, and median (range) Tmax was 6 (4–8), 4 (3–4), and 4 (2–6) hours. Accumulation ratios ranged from 2.4–2.9 for AUC and 2.0–2.2 for Cmax. For QD doses of 450 and 900 mg at D7 and D14, respectively, mean (CV%) Cmax was 64.5 (13.6) and 126 (13.6) μg/mL, and med...