ombitasvir/paritaprevir/ritonavir and dasabuvir

SVR12 is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) \< lower limit of quantification (LLOQ) 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.

SVR12 was defined as 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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in participants in the treatment arm 3-DAA + RBV 600 mg) for 12 weeks compared with the historical control rate for subjects treated with 3-DAA + weight-based RBV for 12 weeks.

The percentage of participants with hemoglobin \<10 g/dL during treatment is provided.

The mean change in hemoglobin (g/L) from baseline to each study visit and to the final treatment visit (up to 12 weeks) is provided.

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity from first dose of study drug until 30 days after the last dose. For more details on AEs please see the Adverse Event section.

SVR24 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of active study drug. The primary efficacy endpoint was superiority of the percentage of treatment-naïve and treatment-experienced HCV subgenotype 1b (GT1b)-infected participants treated with 3-DAA (ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 once daily\] and dasabuvir \[250 mg twice daily\]) who achieved SVR24 compared with the historical control rate for comparable patients treated with telaprevir (TVR) plus pegylated interferon (pegIFN) and RBV.

The changes from week 0 to post-treatment (PT) week 12 in key ISG expression in PBMCs for participants achieving sustained virologic response 12 weeks PT (SVR12) where SVR12 was defined as 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. For each key ISG, fold change was defined as the ratio of the difference between PT Week 12 and baseline expressions over the baseline expression.

The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL.

SVR12, defined as HCV RNA \< lower limit of quantification (LLOQ) in the SVR12 window (12 weeks after the last actual dose of study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Flanking imputation: for participants with missing HCV RNA at a visit who have an undetectable HCV RNA or unquantifiable HCV RNA at the preceding visit and the succeeding visit, the missing value was imputed as undetectable or unquantifiable. For SVR analyses, if there was no value in the window after the flanking imputation but there was an HCV RNA value after the window, then it was imputed into the SVR window. After above imputations were applied, if there was still no value in the window but there was an HCV RNA value from a local laboratory present, then it was imputed into the SVR window. Otherwise, participants with missing data were counted as failures. The 95% confidence interval was calculated using the Wilson score method.

SVR12 was defined as 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.

SVR12 was defined as 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.

Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.

AUC is a measure of how long and how much drug is present in the body after dosing. The amount of ombitasvir present was measured up to 24 hours after dosing.

Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.

Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.

AUC is a measure of how long and how much drug is present in the body after dosing. The amount of paritaprevir present was measured up to 24 hours after dosing.

Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.

Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.

AUC is a measure of how long and how much drug is present in the body after dosing. The amount of dasabuvir present was measured up to 12 hours after dosing. For two subjects in the 15-29 kg group, the 24 h concentration was used as the 12 h concentration due to the significant sampling time deviation. For one subject in the 30-44 kg group, the 24 h concentration was used as the 12 h concentration due to the significant sampling time deviation.

Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.

Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.

AUC is a measure of how long and how much drug is present in the body after dosing. The amount of ritonavir present was measured up to 24 hours after dosing.

Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.

SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) \< lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.

HCV viral kinetics in plasma during therapy were modeled through non-linear mixed effect models, including a rapid first phase of initial decline and a slower second phase decline. The slope of the second phase decline was estimated for each treatment arm.

SVR12 was defined as 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.