Single and Multiple Dose Study of Uprifosbuvir (MK-3682/IDX21437) in Healthy and Hepatitis C Virus (HCV)-Infected Participants (MK-3682-001)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Chronic Hepatitis C

Treatments: Drug: Placebo; Drug: Uprifosbuvir; Drug: Itraconazole

Study type: Interventional

Funder types: Industry

Identifiers

NCT01974687

2013-004043-23 (EudraCT Number)

MK-3682-001 (Other Identifier)

3682-001

IDX-04B-001 (Other Identifier)

U1111-1149-5611 (Other Identifier)

Details and patient eligibility

About

This is a multi-part study to evaluate the safety, tolerability, and pharmacokinetics (PK) of uprifosbuvir (MK-3682/IDX21437) in healthy participants and in participants infected with Hepatitis C virus (HCV) genotype (GT)1-GT6. The effect of food on the PK of uprifosbuvir will be evaluated. The antiviral activity of uprifosbuvir will also be assessed in HCV-infected participants.

Enrollment: 178 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

All Participants:

• of childbearing potential must have agreed to use a double method of birth control (one of which must be a barrier) from Screening through at least 90 days after the last dose of the study drug
• must not have consumed grapefruit or grapefruit juice within 7 days of Day -1 and throughout the study

HCV Participants:

• documented clinical history compatible with chronic hepatitis C.
• have not received direct-acting antiviral treatment for hepatitis C infection
• has HCV Genotype 1, 2, 3, 4, 5 or 6

Exclusion criteria

All Participants:

• pregnant or breastfeeding
• co-infected with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV).
• decompensated liver disease
• other clinically significant medical conditions or laboratory abnormalities.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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178 participants in 6 patient groups

Group A: Healthy

Experimental group

Description:

Healthy participants will receive sequentially higher doses of uprifosbuvir (10 mg - 300 mg) capsules or matching placebo capsules once daily (QD) on Day 1 (Cohorts 1a-3a, 5a), Days 1 and 7 (Cohort 4a), or Day 1 - Day 7 (Cohort 6a). Dosing of next cohort will be based on review of available safety and PK data. Dosing will occur under fasted conditions with the exception of Cohort 4a, in which drug administration will occur under both fasted and fed conditions.

Treatment:

Drug: Placebo

Drug: Uprifosbuvir

Group B: GT1 HCV-infected, treatment naive on Day 1

Experimental group

Description:

HCV GT1 participants with no prior direct-acting antiviral (DAA) exposure will receive a single dose of uprifosbuvir (10 mg - 300 mg) for 1 day across sequential dose cohorts. Dosing will commence following review of available safety and PK data from respective dose cohorts in Group A. All dosing will occur under fasted conditions.

Treatment:

Drug: Uprifosbuvir

Group C: GT1 HCV-infected on Days 1-7

Experimental group

Description:

HCV GT1 participants will receive uprifosbuvir (50 mg - 400 mg in capsules or 300 mg or 450 mg in tablets) or matching placebo capsules QD for 7 days. Dosing will commence following review of available safety and PK data of Group A. Fed vs. fasted dosing will be dependent on food effect results from Group A.

Treatment:

Drug: Placebo

Drug: Uprifosbuvir

Group D: GT2 through GT6 HCV-infected on Days 1-7

Experimental group

Description:

HCV GT2 - GT6 participants will receive uprifosbuvir (50 mg - 300 mg) capsules QD for 7 days. Dosing will commence following review of available safety and PK data from Group A. Fed vs. fasted dosing will be dependent on food effect results from Group A.

Treatment:

Drug: Uprifosbuvir

Group E: GT1 HCV-infected on Days 1-7, mild hepatic impairment

Experimental group

Description:

HCV GT1 participants with mildly impaired hepatic function will receive uprifosbuvir (150 mg - 450 mg) capsules QD for 1 or 7 days. Dosing of subsequent cohorts will be based on review of available safety and PK data. Fed vs. fasted dosing will be dependent on food effect results from Group A.

Treatment:

Drug: Uprifosbuvir

Group F: GT1 HCV-infected on Days 1-7, + Itraconazole

Experimental group

Description:

HCV GT1 participants will receive itraconazole 200 mg twice daily (BID) on Day -5 and itraconazole 200 mg QD from Day -4 to Day 11. Participants will also be co-administered uprifosbuvir 300 mg from Day 1 to Day 7.

Treatment:

Drug: Itraconazole