Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study.
OBJECTIVE
VX-950 specifically inhibits the NS3.4A protease of hepatitis C and has antiviral activity in vitro. This phase I, placebo-controlled, double-blind study evaluated the antiviral activity, pharmacokinetics, and safety of VX-950 in patients with chronic hepatitis C (CHC).


METHODS
Thirty-four patients with genotype 1 CHC were randomized to receive placebo or VX-950 at doses of 450 mg or 750 mg every 8 hours or 1250 mg every 12 hours for 14 days. Of the 34 participants, 27 (79%) had failed prior treatment. Patients were monitored for safety and tolerability of VX-950. Plasma VX-950 concentrations and HCV RNA levels were measured.


RESULTS
VX-950 was well tolerated and had substantial antiviral effects: viral loads dropped > or =2 log(10) in all 28 patients treated with VX-950 and > or =3 log(10) in 26 (93%) of the 28 patients. In the 750-mg-dose group, which had the highest trough plasma drug concentrations, the median reduction of HCV RNA was 4.4 log(10) after 14 days. In the 450-mg and 1250-mg groups, the maximal effect was seen between days 3 and 7 of dosing, and median HCV RNA increased between days 7 and 14; median reductions at day 14 were 2.4 log(10) and 2.2 log(10), respectively. Median alanine aminotransferase levels decreased during dosing in all VX-950 groups.


CONCLUSIONS
VX-950 was well tolerated and demonstrated substantial antiviral activity. Some patients had viral breakthrough during dosing, related to selection of variants with decreased sensitivity to VX-950. The results support further studies of VX-950 in patients with CHC.
Reesink
Hendrik W
HW
Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. h.w.reesink@amc.uva.nl
Zeuzem
Stefan
S
Weegink
Christine J
CJ
Forestier
Nicole
N
van Vliet
Andre
A
van de Wetering de Rooij
Jeroen
J
McNair
Lindsay
L
Purdy
Susan
S
Kauffman
Robert
R
Alam
John
J
Jansen
Peter L M
PL
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010919:Placebos; D012367:RNA, Viral / Q000097:blood*; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
D009842:Oligopeptides; D010919:Placebos; D012367:RNA, Viral; D015842:Serine Proteinase Inhibitors; C486464:telaprevir; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase