title: Randomized, placebo-controlled single-ascending-dose study to evaluate the safety, tolerability and pharmacokinetics of the HIV nucleoside reverse transcriptase inhibitor, BMS-986001, in healthy subjects.
abstract: The objectives of this study were to evaluate the safety, tolerability and pharmacokinetics (PK) of BMS-986001 as a single oral dose in healthy male subjects. Sixty-four healthy male subjects were randomized to receive a single dose of BMS-986001 or placebo in this single-blind, placebo-controlled, sequential ascending-dose study. There were eight treatment groups (10, 30, 100, 300, 600, and 900 mg fed; and 100 and 300 mg fasted) of eight subjects each (BMS-986001 n = 6/placebo n = 2). BMS-986001 was well tolerated, with no serious adverse events (AEs), deaths, or discontinuations due to AEs reported. AEs were experienced by 14.6% of subjects receiving BMS-986001; however, these did not appear to be dose related and were not considered to be related to study drug. BMS-986001 was rapidly absorbed and exhibited a linear dose-exposure relationship across the dose range studied. PK appeared similar whether administered with or without food. Administration of BMS-986001 as a single dose was generally safe and well tolerated. A linear dose-exposure relationship was seen across all doses studied, with no apparent food effect. Further clinical development is warranted.
authors.affiliation: Oncolys BioPharma, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Urata
authors.forename: E
authors.initials: E
authors.lastname: Paintsil
authors.forename: Y-C
authors.initials: YC
authors.lastname: Cheng
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: H
authors.initials: H
authors.lastname: Sevinsky
authors.forename: D
authors.initials: D
authors.lastname: Hawthorne
authors.forename: R
authors.initials: R
authors.lastname: Bertz
authors.forename: G J
authors.initials: GJ
authors.lastname: Hanna
authors.forename: D
authors.initials: D
authors.lastname: Grasela
authors.forename: C
authors.initials: C
authors.lastname: Hwang
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000378:metabolism; D018565:Food-Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016037:Single-Blind Method; D013936:Thymidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; C583040:BMS-986001; D018894:Reverse Transcriptase Inhibitors; D013936:Thymidine
keywords: BMS-986001; human immunodeficiency virus type 1; nucleoside reverse transcriptase inhibitor; pharmacokinetics; safety