Pharmacokinetics of Favipiravir in Volunteers With Hepatic Impairment

A Phase I, Open-Label, Parallel-Group, Multiple-Dose Study to Determine the Pharmacokinetics of Favipiravir in Volunteers With Hepatic Impairment and in Healthy Control Volunteers

This study is designed to determine the pharmacokinetics of favipiravir in volunteers with hepatic impairment and in healthy control volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy; Hepatic Impairment
• Intervention / Treatment: Drug: Favipiravir; Drug: Favipiravir; Drug: Favipiravir

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States
      • University of Miami
    • Orlando, Florida, United States
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hepatically impaired groups:

  • Agree to doctor approved birth control methods from Day 1 until 3 months following the final dose of study drug.
  • Have mild hepatic impairment (Child-Pugh Clinical Assessment Score Grade A, score 5 6) or moderate hepatic impairment (Child-Pugh Clinical Assessment Score Grade B, score 7-9) or severe hepatic impairment (Child-Pugh Clinical Assessment Score Grade C, score 10-15);

• Control group

  • Agree to doctor approved birth control methods from Day 1 until 3 months following the final dose of study drug.
  • Healthy as determined by medical history, physical exam, vital signs, ECGs, and clinical laboratory tests.

Exclusion Criteria:

• Hepatically impaired groups:

  • Have used any drugs known to significantly affect hepatic metabolism within 28 days, or is unable or unwilling to forgo the use of such products throughout the study;
  • Have any acute or unstable condition or disease, other than impaired hepatic function, as determined by medical history, physical exam, ECG and clinical laboratory tests;
  • Known ongoing alcohol and/or drug abuse within 1 month
  • Any evidence of progressive worsening liver function disease as indicated by laboratory values;
  • Have had an acute flare of hepatitis A or B within 6 months;
  • Have acute, fulminant alcoholic hepatitis, determined either clinically or by histology;
  • Have a history of hepatoma or metastatic disease of the liver;

• Control group:

  • Have used any drugs known to significantly affect hepatic metabolism within 28 days, or is unable or unwilling to forgo the use of such products throughout the study;
  • Have a history or presence of clinically cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, hepatic, immunologic, neurologic, oncologic, psychiatric, pulmonary, or renal disease or any other condition.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Normal hepatic function	Drug: Favipiravir; 1200 mg BID for Day 1 + 800 mg BID for Day 2-5; Other Names: T-705a; Drug: Favipiravir; 800 mg BID for Day 1 + 400 mg BID for Day 2-3; Other Names: T-705a; Drug: Favipiravir; 800 mg Single Dose
Experimental: Group 2; Mild hepatic impairment	Drug: Favipiravir; 1200 mg BID for Day 1 + 800 mg BID for Day 2-5; Other Names: T-705a; Drug: Favipiravir; 800 mg BID for Day 1 + 400 mg BID for Day 2-3; Other Names: T-705a; Drug: Favipiravir; 800 mg Single Dose
Experimental: Group 3; Moderate hepatic impairment	Drug: Favipiravir; 1200 mg BID for Day 1 + 800 mg BID for Day 2-5; Other Names: T-705a; Drug: Favipiravir; 800 mg BID for Day 1 + 400 mg BID for Day 2-3; Other Names: T-705a; Drug: Favipiravir; 800 mg Single Dose
Experimental: Group 4; Severe hepatic impairment	Drug: Favipiravir; 1200 mg BID for Day 1 + 800 mg BID for Day 2-5; Other Names: T-705a; Drug: Favipiravir; 800 mg BID for Day 1 + 400 mg BID for Day 2-3; Other Names: T-705a; Drug: Favipiravir; 800 mg Single Dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of favipiravir	The PK parameters for favipiravir and its metabolite in hepatically impaired adult subjects relative to healthy adult subjects matched for age, weight, gender, and race status on Day 1 and on Day 5.	predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 18, 24, 36, 48 hours post-dose on Day 1 and Day 5
AUC of favipiravir	The PK parameters for favipiravir and its metabolite in hepatically impaired adult subjects relative to healthy adult subjects matched for age, weight, gender, and race status on Day 1 and on Day 5.	predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 18, 24, 36, 48 hours post-dose on Day 1 and Day 5

Secondary Outcome Measures

Outcome Measure	Time Frame
vital signs	13 days
electrocardiograms [ECGs]	13 days
clinical laboratory assessment	13 days
adverse events [AEs]	13 days
physical examination	13 days

Collaborators and Investigators

• Sponsor: MDVI, LLC
• Investigators: Principal Investigator: Richard A. Preston, MD/MSHP/MBA, University of Miami

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: August 10, 2011
• First Submitted That Met QC Criteria: August 17, 2011
• First Posted (Estimate): August 18, 2011

Study Record Updates

• Last Update Posted (Estimate): October 22, 2015
• Last Update Submitted That Met QC Criteria: October 20, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Healthy; Favipiravir; hepatic impairment; T-705a
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Anti-Infective Agents; Antiviral Agents; Favipiravir
• Other Study ID Numbers: T705aUS109