NCT03832426

A Pharmacokinetic Study of Narlaprevir as a Single Dose or With Ritonavir Combination in Patients With Hepatic Impairment and Healthy Matched Volunteers

An Open Label, Parallel Design Study to Assess the Pharmacokinetics of Narlaprevir 200 mg as a Single Oral Dose and in Combination With Ritonavir 100 mg in Patients With Hepatic Impairment and Healthy Matched Volunteers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: R-Pharm · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Accepted

Summary

This study was conducted to evaluate narlaprevir (NVR) pharmacokinetics (PK) after a single dose with or without ritonavir (RTV) in cirrhotic Child-Pugh class A patients without active HCV infection versus healthy subjects as well as to assess safety and tolerability of such treatment combination.

Detailed description

The objective of this study was to evaluate PK after a single oral dose of NVR alone and in combination with RTV in patients with compensated liver cirrhosis and in matched healthy controls. The study consisted of 2 parts. In Part I of the study, 8 patients with compensated cirrhosis (Child-Pugh Class A) and 8 matched healthy adult subjects received single doses of NVR at 200 mg with 240 ml of water after a standard breakfast. The 200-mg NVR dose was chosen since this is the intended therapeutic dose. Blood and urine samples were obtained to determine narlaprevir concentration in plasma and urine. As an additional safety precaution, patients with Child-Pugh Class A hepatic impairment were studied successively in Part I and Part II on the basis of the results of an interim safety analysis data and PK data. Based on the results of the interim analysis after the Part I of the study, it was decided to reduce the dose of narlaprevir from baseline 200 mg to 100 mg in Part II of the study. In part 2 of the study, 8 patients with compensated cirrhosis (Child-Pugh Class A) and 8 healthy subjects received NVR at 100 mg in combination with RTV at 100 mg with 240 ml of water after a standard breakfast. Blood and urine samples were obtained to determine narlaprevir concentration, its metabolite and ritonavir in plasma and urine. The total duration of the study for each subject was a maximum of 35 days.

Conditions

• Hepatic Impairment

Interventions

Type	Name	Description
DRUG	Narlaprevir	100 mg film-coated tablets
DRUG	Ritonavir	100 mg film-coated tablets

Timeline

• Start date: 2013-11-08
• Primary completion: 2014-10-24
• Completion: 2014-10-24
• First posted: 2019-02-06
• Last updated: 2019-05-22

Locations

3 sites across 2 countries: Georgia, Russia