BACKGROUND: The aim of this study is to explore the efficacy, safety and pharmacokinetics of 750 mg telaprevir (TVR) given at 8 or 12 h intervals during triple therapy with pegylated interferon-α2b (PEG-IFN) and ribavirin (RBV) for patients with chronic HCV infection. METHODS: A total of 52 patients with high viral loads of HCV genotype 1b who were expected to respond well to therapy (rs8099917 TT genotype or relapse to previous therapy) were randomly assigned to two groups who were given 750 mg TVR at either 8 h (q8h) or 12 h (q12h) intervals in combination with PEG-IFN and RBV for 12 weeks, followed by 12 additional weeks of treatment with PEG-IFN and RBV alone. The primary end point of the study was undetectable HCV RNA at 12 weeks after the end of treatment (sustained virological response [SVR]12). RESULTS:SVR12 rates were 92.3% (24/26) for both q8h and q12h. The changes in mean log10 HCV RNA levels and viral response were also similar in q8h compared to q12h, whereas pharmacokinetic properties such as maximum plasma concentration, area under the concentration-time curve at 24 h and trough plasma concentration of TVR were slightly higher in q8h than in q12h (P>0.2). The frequency of TVR discontinuation due to anaemia or renal damage was significantly higher in q12h than in q8h (6/26 [23%] versus 0/20 [0%], respectively; P=0.02). CONCLUSIONS:TVR given at 12 h intervals should be considered for patients with lower body weight, especially patients with prior relapse and with IL28B polymorphisms at rs8099917 TT (interferon-λ 4 ss469415590 polymorphism TT/TT) genotype in patients with genotype 1b HCV infection.
RCT Entities:
BACKGROUND: The aim of this study is to explore the efficacy, safety and pharmacokinetics of 750 mg telaprevir (TVR) given at 8 or 12 h intervals during triple therapy with pegylated interferon-α2b (PEG-IFN) and ribavirin (RBV) for patients with chronic HCV infection. METHODS: A total of 52 patients with high viral loads of HCV genotype 1b who were expected to respond well to therapy (rs8099917 TT genotype or relapse to previous therapy) were randomly assigned to two groups who were given 750 mg TVR at either 8 h (q8h) or 12 h (q12h) intervals in combination with PEG-IFN and RBV for 12 weeks, followed by 12 additional weeks of treatment with PEG-IFN and RBV alone. The primary end point of the study was undetectable HCV RNA at 12 weeks after the end of treatment (sustained virological response [SVR]12). RESULTS: SVR12 rates were 92.3% (24/26) for both q8h and q12h. The changes in mean log10 HCV RNA levels and viral response were also similar in q8h compared to q12h, whereas pharmacokinetic properties such as maximum plasma concentration, area under the concentration-time curve at 24 h and trough plasma concentration of TVR were slightly higher in q8h than in q12h (P>0.2). The frequency of TVR discontinuation due to anaemia or renal damage was significantly higher in q12h than in q8h (6/26 [23%] versus 0/20 [0%], respectively; P=0.02). CONCLUSIONS:TVR given at 12 h intervals should be considered for patients with lower body weight, especially patients with prior relapse and with IL28B polymorphisms at rs8099917 TT (interferon-λ 4 ss469415590 polymorphism TT/TT) genotype in patients with genotype 1b HCV infection.
Authors: Sathej M Gopalakrishnan; Akshanth R Polepally; Sven Mensing; Amit Khatri; Rajeev M Menon Journal: Clin Pharmacokinet Date: 2017-01 Impact factor: 6.447