Gastroenterology. 2013 Dec 4. pii: S0016-5085(13)01728-9. doi: 10.1053/j.gastro.2013.11.047. [Epub ahead of print]
Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain. Electronic address: email@example.com.
BACKGROUND & AIMS: We performed an open-label, multi-center, Phase 3 study of the safety and efficacy of twice-daily telaprevir in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype 1 infection, including those with cirrhosis.
METHODS: Patients were randomly assigned to groups given telaprevir 1125 mg twice-daily or 750 mg every 8 hrs, plus peg-interferon alfa-2a and ribavirin for 12 weeks; patients were then given peg-interferon alfa-2a and ribavirin alone for 12 weeks if their week 4 level of HCV RNA was <25 IU/mL, or for 36 weeks if their level was higher. The primary objective was noninferiority of telaprevir twice-daily vs every 8 hrs in producing a sustained virologic response 12 weeks after the end of therapy (SVR12) (based on a -11% lower limit of the 95% lower confidence interval for the difference between groups).
RESULTS: At baseline, of 740 patients, 85% had levels of HCV RNA ≥800,000 IU/mL, 28% had fibrosis (F3-4), 14% had cirrhosis (F4), 57% were infected with HCV genotype 1a, and 71% had the non-CC IL28B genotype. Of patients who received telaprevir twice-daily, 74.3% achieved SVR12, compared with 72.8% of patients who received telaprevir every 8 hrs (difference in response, 1.5%; 95% confidence interval, -4.9% to 12.0%), so telaprevir twice-daily is noninferior to telaprevir every 8 hrs. All subgroups of patients who received telaprevir twice-daily vs those who received it every 8 hrs had similar rates of SVR12. Most frequent adverse events (AEs) in the telaprevir phase were fatigue (47%), pruritus (43%), anemia (42%), nausea (37%), rash (35%), and headache (26%); serious AEs were reported in 9% of patients. Rates of AEs and serious AEs were similar or slightly higher among patients receiving telaprevir every 8 hrs.
CONCLUSIONS: Based on a phase 3 trial, telaprevir twice-daily is noninferior to every 8 hrs in producing SVR12, with similar levels of safety and tolerability. These results support use of telaprevir twice-daily in patients with chronic HCV genotype 1 infection, including those with cirrhosis. ClinicalTrials.gov number: NCT01241760.
Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS: AEs, AUC, BMI, C(max), C(max,ss), C(min), C(trough,ss), CI, DAA, DRESS, ESA, G1, HCV, ITT, IU, LLOQ, OPTIMIZE, P, Peg-IFN, PK, PP, PR, R, RBV, RVR, SD, SE, SSC, SVR, TVR, adverse events, area under curve, bid, body mass index, clinical trial, confidence interval, drug reaction with eosinophilia and systemic symptoms, e-diary, eRVR, electronic diary, erythropoiesis-stimulating agents, every 12 hours, every 8 hours, extended rapid virologic response, genotype 1, hepatitis C virus, intent-to-treat, international unit, lower limit of quantification, maximum concentration, maximum steady-state concentration, peginterferon, peginterferon alfa/ribavirin, per-protocol, pharmacokinetics, predose concentration, predose steady-state concentration, protease inhibitor, q12h, q8h, rapid virologic response, ribavirin, special search category, standard deviation, standard error, sustained virologic response, telaprevir, twice dailyPMID: 24316262 [PubMed - as supplied by publisher]