April 11, 2015

Journal of Hepatology

Articles in Press

Jacob Lalezari, J. Greg Sullivan, Peter Varunok, Edward Galen, Kris V. Kowdley, Vinod Rustgi, Humberto Aguilar, Franco Felizarta, Barbara McGovern, Martin King, Akshanth R. Polepally, Daniel E. Cohen

DOI: http://dx.doi.org/10.1016/j.jhep.2015.03.029
Open access funded by the Author(s)
Publication stage: In Press Accepted Manuscript

Publication History

Published Online: March 31, 2015
Accepted: March 25, 2015
Received in revised form: March 17, 2015
Received: September 19, 2014

Abstract

Background & Aims

HCV-infected patients with a history of injection drug use have low rates of initiation and completion of interferon-based therapies. This study evaluated efficacy, safety, and pharmacokinetics of a 12-week all-oral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir +ribavirin in HCV genotype 1-infected patients on stable opioid replacement therapy.

Methods

This was a phase 2, multicenter, open-label, single arm study in treatment-naïve or peginterferon/ribavirin-treatment experienced HCV genotype 1-infected patients on methadone or buprenorphine +/-naloxone. Patients received 12 weeks of co-formulated ombitasvir/paritaprevir/ritonavir(25mg/150mg/100mg once daily) and dasabuvir(250mg twice daily) +weight-based ribavirin. The primary efficacy endpoint was sustained virologic response 12 weeks post-treatment.

Results

Thirty-eight non-cirrhotic patients on chronic methadone(n=19) or buprenorphine(n=19) were enrolled. A total of 37 patients(97.4%) had a sustained virologic response 12 weeks post-treatment. No patient had a viral breakthrough or relapse. One patient discontinued due to serious adverse events unrelated to study drug (cerebrovascular accident and sarcoma). The most frequent adverse events were nausea, fatigue, and headache. Eight patients had on-treatment hemoglobin concentrations <10g/dL. Pharmacokinetic analyses indicated no clinically meaningful impact of methadone or buprenorphine on ombitasvir, paritaprevir, ritonavir, dasabuvir, or dasabuvir M1 metabolite exposures. No dose adjustments of methadone or buprenorphine were required

Conclusions

The interferon-free regimen of ombitasvir/paritaprevir/r and dasabuvir +ribavirin for 12 weeks was well-tolerated and achieved sustained virologic response in 97.4% of patients on opioid substitution therapy in this study. This all-oral regimen may provide an effective alternative to interferon-based therapies for HCV-infected patients with a history of injection drug use.

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