title: Phase 2a randomized controlled trial of short-term activity, safety, and pharmacokinetics of a novel nonnucleoside reverse transcriptase inhibitor, RDEA806, in HIV-1-positive, antiretroviral-naive subjects.
abstract: RDEA806 is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with potent in vitro activity against wild-type and NNRTI-resistant HIV-1. A phase 2a randomized, double-blind, placebo-controlled, dose-escalating study evaluated the short-term antiviral activity, safety, and pharmacokinetics (PKs) of RDEA806 monotherapy in antiretroviral-naïve, HIV-1-infected subjects. The subjects were randomized to four cohorts comprising four dosage regimens and two formulations of RDEA806 or placebo in a 3:1 ratio within each cohort. The investigators were blinded to the results for each cohort. The subjects received RDEA806 or placebo for 7 days. The primary end point was the change in the HIV RNA load from the baseline to day 9 for each of the four RDEA806 dose regimens compared to that achieved with placebo. The RDEA806 PKs and the immune response to RDEA806 were evaluated along with the safety and tolerability of each dose. Of a total of 48 enrolled subjects, 36 subjects (9 in each cohort) were randomized to RDEA806 study drug, and 12 (3 in each cohort) took placebo. A statistically significant decrease in the viral load from the baseline to day 9 was observed for all RDEA806 treatment groups (P<0.001). On day 9, the mean changes in the HIV RNA load from that at the baseline were -1.95 log10 copies/ml (400 mg twice a day), -1.39 log10 copies/ml (600 mg once a day [q.d.]), -1.62 log10 copies/ml (800 mg q.d.), and -1.70 log1) copies/ml (1,000 mg q.d.). The pharmacokinetics were linear and dose proportional. Treatment with RDEA806 was well tolerated, and there were no discontinuations due to adverse events. In conclusion, all doses of RDEA806 were safe and well tolerated and exhibited robust antiretroviral activity in this short-term monotherapy study with antiretroviral-naïve HIV-infected subjects. RDEA806 is a potent and promising novel NNRTI.
authors.affiliation: Department of HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom. gm@moyleg.demon.co.uk
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stoehr
authors.forename: Armin
authors.initials: A
authors.lastname: Rieger
authors.forename: Zancong
authors.initials: Z
authors.lastname: Shen
authors.forename: Kimberly
authors.initials: K
authors.lastname: Manhard
authors.forename: Beth
authors.initials: B
authors.lastname: Sheedy
authors.forename: Vijay
authors.initials: V
authors.lastname: Hingorani
authors.forename: Anneke
authors.initials: A
authors.lastname: Raney
authors.forename: Mai
authors.initials: M
authors.lastname: Nguyen
authors.forename: Tranh
authors.initials: T
authors.lastname: Nguyen
authors.forename: Voon
authors.initials: V
authors.lastname: Ong
authors.forename: Li-Tain
authors.initials: LT
authors.lastname: Yeh
authors.forename: Barry
authors.initials: B
authors.lastname: Quart
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors