nt, confirmed increase from nadir in HCV RNA > 1 log10 IU/mL during treatment, or HCV RNA ≥ 25 IU/mL persistently during treatment with at least 6 weeks of treatment.
b. Relapse was defined as confirmed HCV RNA ≥ 25 IU/mL post-treatment before or during SVR12 window among subjects with HCV RNA less than 25 IU/mL at last observation during at least 11 weeks of treatment.
c. Other includes subjects not achieving SVR12 but not experiencing on-treatment VF or relapse (e.g. missing HCV RNA values in the SVR12 window).
* Ombitasvir tablets, paritaprevir tablets and ritonavir capsules administered separately.
Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with Viekirax in one or more subsets of the paediatric populations in the treatment of chronic hepatitis C (see section 4.2 for information on paediatric use).
The pharmacokinetic properties of the combination of Viekirax with dasabuvir have been eva luated in healthy adult subjects and in subjects with chronic hepatitis C. Table 17 shows mean Cmax and AUC of Viekirax 25 mg/150 mg/100 mg once daily with dasabuvir 250 mg twice daily following multiple doses with food in healthy volunteers.
Table 17. Geometric mean Cmax, AUC of multiple doses of Viekirax 150 mg/100 mg/25 mg once daily with dasabuvir 250 mg twice daily with food in healthy volunteers
Absorption
Ombitasvir, paritaprevir and ritonavir were absorbed after oral administration with mean Tmax of approximately 4 to 5 hours. While ombitasvir exposures increased in a dose proportional manner, paritaprevir and ritonavir exposures increased in a more than dose proportional manner. Accumulation is minimal for ombitasvir and approximately 1.5- to 2-fold for ritonavir and paritaprevir. Pharmacokinetic steady state for the combination is achieved after approximately 12 days of dosing.
The absolute bioavailability of ombitasvir and paritaprevir was approximately 50% when administered with food as Viekirax.
Effect of paritaprevir/ritonavir on ombitasvir and dasabuvir
In the presence of paritaprevir/ritonavir, dasabuvir exposures decreased by approximately 50% to 60% while ombitasvir exposures increased by 31-47%.
Effect of ombitasvir on paritaprevir/ritonavir and dasabuvir
In the presence of ombitasvir, paritaprevir exposures were minimally affected (5% to 27% change) while dasabuvir exposures increase by approximately 30%.
Effect of dasabuvir on paritaprevir/ritonavir and ombitasvir
In the presence of dasabuvir, paritaprevir exposures increased by 50% to 65% while there was no change in ombitasvir exposures.
Effects of food
Ombitasvir, paritaprevir and ritonavir should be administered with food. All clinical trials with ombitasvir, paritaprevir and ritonavir have been conducted following administration with food.
Food increased the exposure (AUC) of ombitasvir, paritaprevir and ritonavir by up to 82%, 211% and 49%, respectively relative to the fasting state. The increase in exposure was similar regardless of meal type (e.g., high-fat versus moderate-fat) or calorie content (approximately 600 Kcal versus approximately 1000 Kcal). To maximise absorption, Viekirax should be taken with food without regard to fat or calorie content.
Distribution
Ombitasvir, paritaprevir and rit
