ess. 33 out of the 34 subjects (97.1%) achieved SVR12 (96.6% in subjects with genotype 1a infection and 100% in subjects with genotype 1b infection). One subject with HCV genotype 1a infection relapsed post-treatment.
Clinical Trial in patients receiving chronic opioid substitution therapy
In a phase 2, multicentre, open-label, single arm study, 38 treatment-naïve or pegIFN/RBV treatment experienced, non-cirrhotic subjects with genotype 1 infection who were on stable doses of methadone (N=19) or buprenorphine with or without naloxone (N=19) received 12 weeks of Exviera in combination with ombitasvir/paritaprevir/ritonavir and ribavirin. Treated subjects had a median age of 51 years (range: 26 to 64); 65.8% were male and 5.3% were Black. A majority (86.8%) had baseline HCV RNA levels of at least 800,000 IU/mL and a majority (84.2%) had genotype 1a infection; 68.4% had IL28B non-CC genotype; 15.8% had portal fibrosis (F2) and 5.3% had bridging fibrosis (F3); and 94.7% were naïve to prior HCV treatment.
Overall, 37 (97.4%) of 38 subjects achieved SVR12. No subjects experienced on-treatment virologic failure or relapse.
Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with Exviera and ombitasvir/paritaprevir/ritonavir 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 Exviera with ombitasvir/paritaprevir/ritonavir have been eva luated in healthy adult subjects and in subjects with chronic hepatitis C. Table 16 shows mean Cmax and AUC of Exviera 250 mg twice daily with ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily following multiple doses with food in healthy volunteers.
Table 16. Geometric mean Cmax, AUC of multiple doses of Exviera 250 mg twice daily and ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily with food in healthy volunteers
Absorption
Dasabuvir was absorbed after oral administration with mean Tmax of approximately 4 to 5 hours. Dasabuvir exposures increased in a dose proportional manner and accumulation is minimal. Pharmacokinetic steady state for dasabuvir when coadministered with ombitasvir/paritaprevir/ritonavir is achieved after approximately 12 days of dosing.
Effects of food
Dasabuvir should be administered with food. All clinical trials with dasabuvir have been conducted following administration with food.
Food increased the exposure (AUC) of dasabuvir by up to 30% 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, Exviera should be taken with food without regard to fat or calorie content.
Distribution
Dasabuvir is highly bound to plasma proteins. Plasma protein binding is not meaningfully altered in patients with renal or hepatic impairment. The blood to plasma concentration ratios in human ranged from 0.5 to 0.7 indicating that dasabuvir was preferentially distributed in the plasma compartment of whole blood. Dasabuvir was greater than 99.5%, and M1 major metabolite of dasabuvir was 94.5% bound to human plasma proteins over a concentration range of 0.0
