Administration of Telaprevir Twice or 3 Times Daily

Boston—Patients with hepatitis C had similar sustained virologic response rates after 12 weeks whether they took 1125 mg of telaprevir twice daily or 750 mg of telaprevir every 8 hours, according to a randomized, open-label, multicenter, phase 3 trial.

Results were presented during a poster session at The Liver Meeting. The poster was titled OPTIMIZE Trial: Noninferiority of Twice-Daily Telaprevir versus Administration Every 8 Hours in Treatment-Naïve, Genotype 1 HCV-Infected Patients.

In May 2011, the FDA approved telaprevir for use in patients with chronic hepatitis C who had not received interferon-based drug therapy or had not responded to previous therapies. The recommended dosage is 750 mg taken 3 times daily with food. Patients are advised to take the combination of telaprevir, peginterferon alfa, and ribavirin for 12 weeks, followed by 12 or 36 weeks of peginterferon alfa and ribavirin depending on viral response and prior response status, according to the drug’s Prescribing Information.

In this trial, treatment-naïve patients with genotype 1 chronic hepatitis C infection were randomized to receive either 750 mg of telaprevir every 8 hours or 1125 mg of telaprevir twice daily plus peginterferon alfa and ribavirin for 12 weeks. For the next 12 weeks, the patients took only peginterferon alfa and ribavirin. If patients achieved hepatitis C RNA <25 IU/mL, the total treatment duration was 24 weeks. If not, they received treatment for a total of 48 weeks.

The authors defined noninferiority as plasma hepatitis C RNA levels <25 IU/mL at 12 weeks after the last planned dose of the study drug.

Of the 744 patients randomized, all but 4 received treatment: 371 took 750 mg of telaprevir every 8 hours and 369 took 1125 mg of telaprevir twice daily. The baseline characteristics were similar between the groups. Mean age was 48 years, 60% of patients were male, 92% were white, and mean body mass index was 27 kg/m².

The sustained virologic rate after 12 weeks was 74% in the 750-mg telaprevir group and 73% in the 1125-mg telaprevir group, a difference that the authors considered noninferior.

In addition, the sustained virologic rates for patients with cirrhosis were 54% and 49% for those who took 750 mg of telaprevir and 1125 mg of telaprevir, respectively. For patients without cirrhosis, the rates were 78% for the 750-mg telaprevir group and 77% for the 1125-mg telaprevir group.

Relapse rates were also similar: 7% in the 750-mg telaprevir group and 8% in the
1125-mg telaprevir group.

Further, serious adverse events were found in 9% of patients who took 750 mg of telaprevir every 8 hours and 8% of those who received 1125 mg of telaprevir twice daily. During the study, a patient in the 750-mg telaprevir group died due to a brain neoplasm, but the authors indicated that the brain neoplasm was not related to telaprevir, peginterferon alfa or ribavirin. There were no other deaths during the trial.

The most frequent adverse events were fatigue, pruritus, anemia, nausea, rash, and headache.

The authors concluded that because of the similar sustained virologic rates and adverse event rates, patients with genotype 1 hepatitis C might be able to use a simplified dosing regimen.

This study was supported by Tibotec/Janssen Pharmaceuticals, Inc. and Vertex Pharmaceuticals Incorporated.