Makoto Kuboki

Safety and efficacy of faldaprevir with pegylated interferon alfa-2a and ribavirin in Japanese patients with chronic genotype-1 hepatitis C infection

Faldaprevir (BI 201335) is a potent once‐daily (QD) NS3/4A protease inhibitor for the treatment of patients with genotype‐1 (GT‐1) hepatitis C virus (HCV). The aim of this study was to evaluate the safety, pharmacokinetics and efficacy of faldaprevir plus pegylated interferon alfa‐2a (PegIFN) and ribavirin (RBV) in Japanese patients infected with chronic GT‐1 HCV.

Su1058 Early Stopping Rules for Faldaprevir Plus Pegylated Interferon α-2A and Ribavirin in Treatment-Naïve Patients: Exploratory Study of Pooled Data From Phase III Trials

Background: The HCV-PRO is a validated disease-specific patient reported outcome (PRO) instrument. This analysis reports on HCV-infected patient response in a trial of oral DAA therapy and assesses psychometric properties of the French-translated HCV-PRO. Method: French Genotype 1 patients in the multinational AVIATOR trial of interferon-free DAA therapy responded to theHCV-PRO, SF-36v.2, and EQ-5D 5L+VAS. HCV-PROwas translated under Harmonization standards. Approved French-language SF-36 and EQ-5Dwere included for psychometric comparison. Analyses of response were performed at Baseline, week 8 (Wk8), End of Treatment (EOT), and 24 week follow-up (PTW24), and included change from baseline. Internal consistency/reliability of HCV-PRO items and total score were evaluated using Cronbachs alpha. Convergent validity was assessed through Pearsons correlation (0.5-0.9=moderate-strong) to SF-36 MCS/PCS and EQ-5D VAS. Discriminant validity was assessed by dichotomizing HCV-PRO score on EQ-5D Anxiety/Depression and Pain/Discomfort dimensions (none versus some). Results: Demographics (N=58): 48% female, 88% white, 45% ≥50 years of age, 45% Genotype 1a, 86% IL28B non-CC. Clinical response (SVR24) was 93.1%. All PRO scores were minimally changed during treatment (Wk8, EOT). Mean HCV-PRO score at PTW24 was improved (p<0.03) over baseline. Cronbachs alpha for HCV-PRO items and total scores were 0.44-0.95. HCV-PRO total score exhibited moderateto-high correlation with SF-36 MCS/PCS and EQ-5D VAS total scores (r=0.54-0.87). HCVPRO scores were lower in patients with anxiety/depression or pain/discomfort (p<0.01). Conclusion: The French-translated HCV-PRO is a valid, responsive, disease-specific instrument. HCV-PRO score changed minimally during oral DAA treatment and improved over baseline after therapy.

Quantitative Measurement of Fluorescent Intensity of the Rat Liver Surface Using Video Fluorescence Laparoscopy Following Intravenous Fluorescein Injection

Abstract: A new method for the quantitative measurement of fluorescent intensity of the rats liver surface after fluorescein injection is described. The measuring system of fluorescent intensity on the rat liver surface consisted of a video laparoscopy with a video densitometer. An excitation filter was placed in the light source and an absorbing filter was attached to the eyepiece of the magnifying scope in this fluorescence video laparoscopy system. Fluorescein was injected intravenously into the inferior vena cava. Video fluorescence images of the liver surface were recorded with a CCD TV camera which was connected to the scope. In measuring the mean intensity of video images, a region of interest was designated on the TV monitor. The fluorescent intensity in this region was measured by a video densitometer and expressed in volts. The time‐intensity curve was graphically presented using a pen recorder. In this way, the time course of the liver surface fluorescent intensity could be analyzed with data expressed in volts. In normal livers, the fluorescent intensity began to rise 4.0 ± 0.5 seconds after fluorescein injection and reached a peak at 14.4 ± 1.5 seconds. Thereafter, the intensity fell slightly but then rose again to a second peak 170±50 seconds after injection.