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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182965d12
Clinical Science

Randomized Placebo-Controlled Study of the Safety, Tolerability, Antiviral Activity, and Pharmacokinetics of 10-Day Monotherapy With BMS-986001, a Novel HIV NRTI, in Treatment-Experienced HIV-1–Infected Subjects

Cotte, Laurent MD*; Dellamonica, Pierre MD; Raffi, Francois MD, PhD; Yazdanpanah, Yazdan MD, PhD§; Molina, Jean-Michel MD; Boué, François MD; Urata, Yasuo MSc#; Chan, H. Phyllis PhD**; Zhu, Li PhD**; Chang, Ih PhD**; Bertz, Richard PhD**; Hanna, George J. MD**; Grasela, Dennis M. PharmD, PhD**; Hwang, Carey MD, PhD**

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Abstract

Objective: To investigate the safety, tolerability, pharmacokinetics, and antiviral activity of BMS-986001 (a nucleoside reverse transcriptase inhibitor) in treatment-experienced, HIV-1–infected subjects not exposed to antiretroviral treatment in the previous 3 months.

Methods: Thirty-two HIV-1–infected subjects were randomized (3:1) to receive BMS-986001 or placebo once daily for 10 days in this double-blind, placebo-controlled, dose-escalating monotherapy phase IIa study. There were 4 treatment groups (100, 200, 300, and 600 mg, all once daily) of 8 subjects each (BMS-986001, n = 6/placebo n = 2).

Results: BMS-986001 was generally well tolerated, with no discontinuations due to adverse events and no deaths occurring. Adverse events were experienced by 22 of 24 BMS-986001-treated subjects and did not seem to be dose related. The majority were mild and considered unrelated or unlikely to be related to the study drug. The pharmacokinetics of BMS-986001 were dose proportional. Median decrease in plasma HIV-1 RNA from baseline to day 11 was 0.97, 1.15, 1.28, and 1.15 log10 copies/mL for BMS-986001 at 100, 200, 300, and 600 mg, respectively. Plasma area under the curve correlated with the antiviral activity of BMS-986001, indicating that area under the curves produced by 100–600 mg doses were on the upper end of the exposure–response curve. One subject with a single thymidine analog mutation at baseline responded well to BMS-986001.

Conclusions: Administration of BMS-986001 for 10 days resulted in substantial decreases in plasma HIV-1 RNA levels for all dose groups and was generally well tolerated. These data support continued clinical development of BMS-986001 at a dose of 100 mg, once daily or greater.

Trial registration: EUDRACT Number 2008-004810-29.

© 2013 Lippincott Williams & Wilkins, Inc.

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