Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection.

Abstract

BACKGROUND & AIMS:

Therapeutic regimens are being developed for patients with hepatitis C virus (HCV) infection that do not include the combination of peginterferon alfa and ribavirin. We investigated the antiviral effect and safety of BI 201335 (an inhibitor of the NS3/4A protease) and BI 207127 (an inhibitor of the NS5B non-nucleoside polymerase) with ribavirin.

METHODS:

Thirty-two treatment-naïve patients with chronic HCV genotype 1 infection were randomly assigned to groups that were given 400 mg or 600 mg BI 207127 3 times daily plus 120 mg BI 201335 once daily and 1000 to 1200 mg/day ribavirin for 4 weeks. The primary efficacy end point was virologic response (HCV RNA level <25 IU/mL at week 4). Thirty-two patients received treatment; 31 completed all 4 weeks of assigned combination therapy.

RESULTS:

In the group given BI 207127 400 mg 3 times daily, the rates of virologic response were 47%, 67%, and 73% at days 15, 22, and 29; a higher rate of response was observed in patients with genotype-1b compared with genotype-1a infections. In the group given BI 207127 600 mg 3 times daily, the rates of virologic response were 82%, 100%, and 100%, respectively, and did not differ among genotypes. One patient in the group given 400 mg 3 times daily had virologic breakthrough (≥1 log(10) rebound in HCV RNA) at day 22. The most frequent adverse events were mild gastrointestinal disorders, rash, and photosensitivity. There were no severe or serious adverse events; no patients discontinued therapy prematurely.

CONCLUSIONS:

The combination of the protease inhibitor BI 201335, the polymerase inhibitor BI 207127, and ribavirin has rapid and strong activity against HCV genotype-1 and did not cause serious or severe adverse events.

• Authors: Stefan Zeuzem, Tarik Asselah, Peter Angus, Jean-Pierre Zarski, Dominique Larrey, Beat Müllhaupt, Ed Gane, Marcus Schuchmann, Ansgar Lohse, Stanislas Pol, Jean-Pierre Bronowicki, Stuart Roberts, Keikawus Arasteh, Fabien Zoulim, Markus Heim, Jerry O Stern, George Kukolj, Gerhard Nehmiz, Carla Haefner, Wulf Otto Boecher
• Journal: Gastroenterology (Gastroenterology) Vol. 141 Issue 6 Pg. 2047-55; quiz e14 (Dec 2011) ISSN: 1528-0012 [Electronic] United States
• PMID: 21925126 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Acrylates
• Aminoisobutyric Acids
• Antiviral Agents
• Benzimidazoles
• Oligopeptides
• Protease Inhibitors
• Quinolines
• RNA, Viral
• Thiazoles
• Viral Nonstructural Proteins
• Ribavirin
• deleobuvir
• faldaprevir
• Proline
• NS-5 protein, hepatitis C virus
• RNA-Dependent RNA Polymerase
• Leucine

Topics

• Acrylates (adverse effects, therapeutic use)
• Aminoisobutyric Acids
• Antiviral Agents (adverse effects, therapeutic use)
• Benzimidazoles (adverse effects, therapeutic use)
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Leucine (analogs & derivatives)
• Male
• Middle Aged
• Oligopeptides (adverse effects, therapeutic use)
• Proline (analogs & derivatives)
• Protease Inhibitors (adverse effects, therapeutic use)
• Quinolines
• RNA, Viral (analysis, blood, drug effects)
• RNA-Dependent RNA Polymerase (antagonists & inhibitors)
• Ribavirin (adverse effects, therapeutic use)
• Thiazoles (adverse effects, therapeutic use)
• Treatment Outcome
• Viral Load
• Viral Nonstructural Proteins (antagonists & inhibitors)