TY - JOUR
T1 - Safety, Tolerability, and Pharmacokinetics of KP-1461 in Phase I Clinical Studies
T2 - A Single Oral Dose Study in Non-HIV-Infected Adults, and a 14-Day Dose-Escalating Study in Highly Antiretroviral-Experienced HIV-Infected Adults
AU - Clay, Patrick G.
AU - Mcrae, Marypeace
AU - Laurent, Jean Pierre
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: NCT00504452 ( http://clinicaltrials.gov/ct2/show/NCT00504452?term=KP-1461&rank=1 ) was sponsored in total by the drug manufacturer, Koronis Pharmaceuticals.
PY - 2011/8
Y1 - 2011/8
N2 - 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) and KP-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.
AB - 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) and KP-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.
KW - HIV/AIDS
KW - KP-1212
KW - KP-1461
KW - antiretroviral
KW - pharmacokinetics
KW - phase I
UR - http://www.scopus.com/inward/record.url?scp=80052836937&partnerID=8YFLogxK
U2 - 10.1177/1545109711406442
DO - 10.1177/1545109711406442
M3 - Review article
C2 - 21593403
AN - SCOPUS:80052836937
SN - 2325-9574
VL - 10
SP - 232
EP - 238
JO - Journal of the International Association of Providers of AIDS Care (JIAPAC)
JF - Journal of the International Association of Providers of AIDS Care (JIAPAC)
IS - 4
ER -