BACKGROUND:KP-1461 is a prodrug to KP-1212. KP-1212 is a viral mutagen designed to increase viral error rate. METHODS: We describe 2 phase I studies: KP1461-101 (double-blind, placebo-controlled, single, escalating doses, 100 to 1600 mg study in 42 non-HIV-infected participants) andKP-1461-102 (double-blind placebo-controlled dose escalation 14-day study in HIV-infected participants, 400-3200 mg). Primary objectives were safety/tolerability. Secondary objectives included pharmacokinetic analysis with exploratory objective to characterize KP-1212 effects on viral load. RESULTS:KP-1461 was well tolerated. Majority of adverse events were grade 1 (neurological, gastrointestinal, cardiovascular). Four participants experienced grade 3 and 1 experienced a grade 4 event. Analysis demonstrated no difference in pharmacokinetic parameters at day 1 or 14. Linear pharmacokinetics found in 1600 mg arm. Compared to placebo, only at the 3200 mg dose demonstrated a marginally statistically significant virologic response. CONCLUSIONS: These studies provide safety/tolerability information and suggest virologic efficacy. KP-1212, a first-in-class antiretroviral, demonstrates the ability to induce viral eradication in vitro. Viral reduction in vivo may foretell a paradigm shift in HIV pharmacotherapy.
RCT Entities:
BACKGROUND: KP-1461 is a prodrug to KP-1212. KP-1212 is a viral mutagen designed to increase viral error rate. METHODS: We describe 2 phase I studies: KP1461-101 (double-blind, placebo-controlled, single, escalating doses, 100 to 1600 mg study in 42 non-HIV-infectedparticipants) and KP-1461-102 (double-blind placebo-controlled dose escalation 14-day study in HIV-infectedparticipants, 400-3200 mg). Primary objectives were safety/tolerability. Secondary objectives included pharmacokinetic analysis with exploratory objective to characterize KP-1212 effects on viral load. RESULTS: KP-1461 was well tolerated. Majority of adverse events were grade 1 (neurological, gastrointestinal, cardiovascular). Four participants experienced grade 3 and 1 experienced a grade 4 event. Analysis demonstrated no difference in pharmacokinetic parameters at day 1 or 14. Linear pharmacokinetics found in 1600 mg arm. Compared to placebo, only at the 3200 mg dose demonstrated a marginally statistically significant virologic response. CONCLUSIONS: These studies provide safety/tolerability information and suggest virologic efficacy. KP-1212, a first-in-class antiretroviral, demonstrates the ability to induce viral eradication in vitro. Viral reduction in vivo may foretell a paradigm shift in HIV pharmacotherapy.
Authors: Jonathan M Rawson; Richard H Heineman; Lauren B Beach; Jessica L Martin; Erica K Schnettler; Michael J Dapp; Steven E Patterson; Louis M Mansky Journal: Bioorg Med Chem Date: 2013-08-20 Impact factor: 3.641
Authors: Charles Hicks; Patrick Clay; Robert Redfield; Jay Lalezari; Ralph Liporace; Stefan Schneider; Michael Sension; MaryPeace McRae; Jean-Pierre Laurent Journal: AIDS Res Hum Retroviruses Date: 2012-08-27 Impact factor: 2.205