Open-label phase 2 study of faldaprevir, deleobuvir and ribavirin in Japanese treatment-naive patients with chronic hepatitis C virus genotype 1 infection.

AIM: The safety and efficacy of the NS3/4A protease inhibitor faldaprevir in combination with the non-nucleoside NS5B polymerase inhibitor deleobuvir and ribavirin in Japanese treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) infection was evaluated. METHODS: In this multicenter, open-label phase 2 study, patients were assigned to 8 weeks of treatment with 80 mg (group 1) or 120 mg (group 2) faldaprevir once daily (q.d.) in combination with deleobuvir 600 mg twice daily and weight-based ribavirin. This was followed by a 24-week treatment with faldaprevir 120 mg q.d. in combination with peginterferon-α-2a and ribavirin. The primary objective was safety; virological response at weeks 4 and 8 was a secondary endpoint. RESULTS: Twelve and 13 patients were treated in group 1 and 2, respectively; all were infected with HCV genotype 1b. All patients experienced a drug-related adverse event (AE). The frequency of individual events was generally numerically greater in group 2 than 1. The most common AEs were nausea (66.7%, group 1; 76.9%, group 2) and vomiting (33.3%, group 1; 61.5%, group 2). Virological response at weeks 4 and 8 was achieved by 11 (91.7%) patients in group 1; in group 2, 12 (92.3%) patients achieved virological response at week 4 and all at week 8. All patients who achieved the week 8 endpoint achieved sustained virological response at week 12. CONCLUSION: Faldaprevir 80 or 120 mg q.d. in combination with deleobuvir and ribavirin was tolerable and had similar efficacy in Japanese patients with HCV genotype 1 infection. ClinicalTrials.gov: NCT01528735.

Reliability study on the Japanese version of the Clinician's Interview-Based Impression of Change.

The Japanese version of the Clinician's Interview-Based Impression of Change (CIBIC-plus J) is a semistructured interview format including a 7-point Likert type scale for the Clinician's Global Impression of Change. It comprises subscales of DAD for ADL, Behave-AD for behavioral and psychiatric symptoms and MENFIS for cognitive and emotional impairment. DAD and Behave-AD are used for caregivers and MENFIS for both caregivers and patients. The objective of this study was to examine the interrater reliability of the CIBIC-plus J by the videotape method. Twenty videotaped patients including 13 real and 7 virtual patients were independently assessed by 11 raters. The kappa coefficient from the full set of data of 20 patients and 11 raters was 0.453, and from the limited data of 13 real patients, 0.383. By permitting one-point disagreements on the 7-point scale or by collapsing it into the 3-point scale (improved, no change, or worsened), kappa improved to 0.894 and 0.731, or 0.734 and 0.504, respectively. From these results, it was concluded that the reliability of a 7-point Clinician's Global Impression of Change was halfway, i.e., neither sufficient nor insufficient. However, if one-point disagreements or collapsing into 3-point scale are allowable, the CIBIC-plus J will be sufficiently reliable.