Pharmacokinetics of Favipiravir in Volunteers With Hepatic Impairment

• Cmax of favipiravir [ Time Frame: 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 ] [ Designated as safety issue: No ]
  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.
• AUC of favipiravir [ Time Frame: 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 ] [ Designated as safety issue: No ]
  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.

• vital signs [ Time Frame: 13 days ] [ Designated as safety issue: Yes ]
• electrocardiograms [ECGs] [ Time Frame: 13 days ] [ Designated as safety issue: Yes ]
• clinical laboratory assessment [ Time Frame: 13 days ] [ Designated as safety issue: Yes ]
• adverse events [AEs] [ Time Frame: 13 days ] [ Designated as safety issue: Yes ]
• physical examination [ Time Frame: 13 days ] [ Designated as safety issue: Yes ]

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

• Healthy
• Hepatic Impairment

• Drug: Favipiravir
  1200 mg BID for Day 1 + 800 mg BID for Day 2-5
  Other Name: T-705a
• Drug: Favipiravir
  800 mg BID for Day 1 + 400 mg BID for Day 2-3
  Other Name: T-705a
• Drug: Favipiravir
  800 mg Single Dose

• Experimental: Group 1
  Normal hepatic function
  Interventions:

  • Drug: Favipiravir
  • Drug: Favipiravir
• Experimental: Group 2
  Mild hepatic impairment
  Intervention: Drug: Favipiravir
• Experimental: Group 3
  Moderate hepatic impairment
  Intervention: Drug: Favipiravir
• Experimental: Group 4
  Severe hepatic impairment
  Interventions:

  • Drug: Favipiravir
  • Drug: Favipiravir

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.