PMID- 21095483
OWN - NLM
STAT- MEDLINE
DCOM- 20110304
LR  - 20201209
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 32
IP  - 11
DP  - 2010 Oct
TI  - Safety and tolerability of lersivirine, a nonnucleoside reverse transcriptase 
      inhibitor, during a 28-day, randomized, placebo-controlled, Phase I clinical 
      study in healthy male volunteers.
PG  - 1889-95
LID - 10.1016/j.clinthera.2010.10.007 [doi]
AB  - BACKGROUND: Lersivirine is a nonnucleoside reverse transcriptase inhibitor 
      undergoing clinical development for the treatment of HIV-1. OBJECTIVE: The goal 
      of this study was to investigate the safety and tolerability of multiple oral 
      doses of lersivirine administered to healthy male subjects to assist in the 
      planning of longer term studies. METHODS: This was a randomized, double-blind, 
      double-dummy, placebo-controlled, parallel-group, multicenter, Phase I clinical 
      study in fasting, healthy male volunteers. Subjects were randomly assigned in a 
      ratio of 7:7:4:4 to receive lersivirine 500 mg BID, lersivirine 750 mg once 
      daily, efavirenz 600 mg once daily, or placebo once daily for 28 days. Safety and 
      tolerability were assessed throughout the study by continuous collection of 
      adverse events (AEs), including adverse drug reactions, illnesses with onset 
      during the study, exacerbation of previous illnesses, and clinically significant 
      changes in physical examination findings. Vital sign measurements and ECGs were 
      performed at screening; on day 1 (predose and 2, 3, and 4 hours postdose); on 
      days 7, 14, 21, and 28 (predose); at discharge; and at follow-up. Safety 
      laboratory tests (including hematology, chemistry, and urinalysis) were performed 
      at screening; days 0, 7, 14, 21, and 27; and at follow-up. RESULTS: Of the 66 
      healthy male subjects enrolled (age range, 21-51 years; body mass index, 
      18.1-29.9 kg/m(2)), 40 were white, 22 were Asian, 3 were black, and 1 was of 
      mixed race. There were no clinically significant laboratory abnormalities, 
      including changes in lipid profile, liver or renal function test results, or ECG 
      findings. Overall, 86% (18/21) of subjects in the lersivirine 500-mg BID group, 
      81% (17/21) in the lersivirine 750-mg once-daily group, 92% (11/12) in the 
      efavirenz 600-mg once-daily group, and 92% (11/12) in the placebo group 
      experienced at least one treatment-related AE. Eight subjects were permanently 
      discontinued from the study; 4 subjects in the efavirenz group (3 of whom 
      participated in the trial at the Brussels study center) were permanently 
      discontinued due to AEs considered to be treatment related. No subjects receiving 
      lersivirine permanently discontinued the study due to treatment-related AEs, 
      although one subject temporarily discontinued treatment. In addition, 4 subjects 
      withdrew consent (2 subjects [1 of whom was at the Brussels study center] 
      receiving lersivirine 750 mg once daily and 2 subjects [1 of whom was at the 
      Brussels study center] receiving efavirenz). There were no deaths or serious AEs 
      in any of the study groups. CONCLUSION: Lersivirine appeared to be well tolerated 
      after 28 days of continuous dosing in this small, selected group of young, 
      healthy male volunteers.
CI  - Copyright (c) 2010 Excerpta Medica Inc. All rights reserved.
FAU - Davis, John
AU  - Davis J
AD  - Research Clinical Pharmacology, Pfizer Inc, Sandwich, Kent, United Kingdom. 
      john.davis@pfizer.com
FAU - Hackman, Frances
AU  - Hackman F
FAU - Ndongo, Marie-Noella
AU  - Ndongo MN
FAU - Choo, HengWee
AU  - Choo H
FAU - Lewis, Drew
AU  - Lewis D
FAU - Tawadrous, Margaret
AU  - Tawadrous M
FAU - Goodrich, James
AU  - Goodrich J
FAU - Langdon, Grant
AU  - Langdon G
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Alkynes)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Benzoxazines)
RN  - 0 (Cyclopropanes)
RN  - 0 (Nitriles)
RN  - 0 (Pyrazoles)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 0 (UK 453,061)
RN  - JE6H2O27P8 (efavirenz)
SB  - IM
MH  - Adult
MH  - Alkynes
MH  - Anti-HIV Agents/administration & dosage/*adverse effects
MH  - Benzoxazines/adverse effects
MH  - Cyclopropanes
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nitriles/administration & dosage/*adverse effects
MH  - Pyrazoles/administration & dosage/*adverse effects
MH  - Reverse Transcriptase Inhibitors/administration & dosage/*adverse effects
MH  - Young Adult
EDAT- 2010/11/26 06:00
MHDA- 2011/03/05 06:00
CRDT- 2010/11/25 06:00
PHST- 2010/09/16 00:00 [accepted]
PHST- 2010/11/25 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2011/03/05 06:00 [medline]
AID - S0149-2918(10)00346-2 [pii]
AID - 10.1016/j.clinthera.2010.10.007 [doi]
PST - ppublish
SO  - Clin Ther. 2010 Oct;32(11):1889-95. doi: 10.1016/j.clinthera.2010.10.007.