December 13, 2013

Gastroenterology. 2013 Dec 4. pii: S0016-5085(13)01728-9. doi: 10.1053/j.gastro.2013.11.047. [Epub ahead of print]

Buti M, Agarwal K, Horsmans Y, Sievert W, Janczewska E, Zeuzem S, Nyberg L, Brown RS Jr, Hezode C, Rizzetto M, Parana R, De Meyer S, De Masi R, Luo D, Bertelsen K, Witek J.

Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain. Electronic address: mbuti@vhebron.net.

Abstract

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 daily

PMID: 24316262 [PubMed - as supplied by publisher]
Source

0 comments :

Post a Comment