cted Subjects in TURQUOISE-I
a. On-treatment VF was defined as confirmed HCV ≥ 25 IU/mL after HCV RNA < 25 IU/mL during treatment, confirmed 1 log10 IU/mL increase in HCV RNA from nadir, or HCV RNA persistently ≥ 25 IU/mL 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 < 25 IU/mL at last observation during at least 11 weeks of treatment.
c. These virologic failures appear to have resulted from reinfection based on analyses of baseline and virologic failure samples
d. Other includes subjects not achieving SVR12 but not experiencing on-treatment VF or relapse (e.g. missing HCV RNA values in the SVR12 window).
In TURQUOISE-I, the SVR12 rates in HCV/HIV-1 co-infected subjects were consistent with SVR12 rates in the phase 3 trials of HCV mono-infected subjects. 7 of 7 subjects with genotype 1b infection and 51 of 56 subjects with genotype 1a infection achieved SVR12. 5 of 6 subjects with compensated cirrhosis in each arm achieved SVR12.
Clinical Trial in liver transplant recipients
In the CORAL-1 study, the safety and efficacy of Exviera and ombitasvir/paritaprevir/ritonavir with ribavirin for 24 weeks was studied in 34 HCV genotype 1-infected liver transplant recipients who were at least 12 months post-transplant at study enrolment. The dose of ribavirin was individualized at the discretion of the investigator, with most patients receiving 600 to 800 mg as a starting dose, and most patients also receiving 600 to 800 mg per day at the end of treatment.
34 subects (29 with HCV genotype 1a infection and 5 with HCV genotype 1b infection) were enrolled who had not received treatment for HCV infection after transplantation and had a METAVIR fibrosis score of F2 or less. 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).
5.2 Pharmacokinetic properties
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 a |
