Jacob Lalezari1, J Greg Sullivan2, Peter Varunok3, Edward Galen4, Kris V Kowdley5, Vinod Rustgi6, Humberto Aguilar7, Franco Felizarta8, Barbara McGovern9, Martin King9, Akshanth R Polepally9, Daniel E Cohen9. 1. Quest Clinical Research, San Francisco, CA, United States. Electronic address: drjay@questclinical.com. 2. Parkway Medical Center, Birmingham, AL, United States. 3. Premier Medical Group of the Hudson Valley, PC, Poughkeepsie, NY, United States. 4. Northwest Gastroenterology Clinic, Portland, OR, United States. 5. Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, United States. 6. Thomas E. Starzl Transplantation Institute, UPMC Montefiore, Pittsburgh, PA, United States. 7. Louisiana Research Center, LLC, Shreveport, LA, United States. 8. Private Practice, Bakersfield, CA, United States. 9. AbbVie Inc., North Chicago, IL, United States.
Abstract
BACKGROUND & AIMS: Hepatitis C virus (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 II, multicenter, open-label, single-arm study in treatment-naïve or peginterferon/ribavirintreatment-experienced HCV genotype 1-infected patients on methadone or buprenorphine±naloxone. Patients received 12weeks 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) orbuprenorphine (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/ritonavir and dasabuvir+ribavirin for 12weeks 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.
RCT Entities:
BACKGROUND & AIMS:Hepatitis C virus (HCV)-infectedpatients 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 II, 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 12weeks 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/ritonavir and dasabuvir+ribavirin for 12weeks 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-infectedpatients with a history of injection drug use.
Authors: Asher J Schranz; Jessica Barrett; Christopher B Hurt; Carlos Malvestutto; William C Miller Journal: Curr HIV/AIDS Rep Date: 2018-06 Impact factor: 5.071
Authors: Akshanth R Polepally; Prajakta S Badri; Doerthe Eckert; Sven Mensing; Rajeev M Menon Journal: Eur J Drug Metab Pharmacokinet Date: 2017-04 Impact factor: 2.441
Authors: Jason Grebely; Geert Robaeys; Philip Bruggmann; Alessio Aghemo; Markus Backmund; Julie Bruneau; Jude Byrne; Olav Dalgard; Jordan J Feld; Margaret Hellard; Matthew Hickman; Achim Kautz; Alain Litwin; Andrew R Lloyd; Stefan Mauss; Maria Prins; Tracy Swan; Martin Schaefer; Lynn E Taylor; Gregory J Dore Journal: Int J Drug Policy Date: 2015-07-17