An Open-label, Single Arm, Phase 2 Study to Evaluate ABT-450/r/ABT-267 and ABT-333 With Ribavirin (RBV) in Adults With Genotype 1 HCV Infection Taking Methadone or Buprenorphine

The percentage of participants with sustained virologic response (plasma hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantification [< LLOQ]) 12 weeks after the last dose of study drug.

Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment) or fail to suppress (HCV RNA ≥ LLOQ) persistently during treatment with at least 6 weeks [≥ 36 days] of treatment.

Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment. Completion of treatment was defined as a study drug duration ≥ 77 days.

Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and were analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC24 in ng*hr/mL)] was estimated using noncompartmental analyses. For ABT-450, ritonavir, and ABT-267, the AUC from time 0 to the last measureable concentration (AUCt in ng*hr/mL) was calculated instead of AUC24 due to time deviations at 24 hours. The AUCt values are approximately equivalent to AUC24. For ABT-333, ABT-333 M1, and RBV, the AUC from time 0 to 12 hours (AUC12 in ng*hr/mL) after the morning dose was calculated using the 24-hour concentration as the 12-hour concentration as dosing was twice a day and a 12-hour sample was not collected in this study.

Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and were analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Maximum plasma concentration (Cmax; measured in ng/mL) was directly determined from the concentration-time data.

Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. The time to maximum plasma concentration (Tmax; measured in hours) was directly determined from the concentration-time data.

Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Minimum plasma concentration (C trough; measured in ng/mL) was directly determined from the concentration-time data.