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

NCT ID: NCT01974687

Last Updated: 2018-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2015-09-11

Brief Summary

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.

Conditions

Chronic Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group A: Healthy

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.

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Uprifosbuvir 5 mg, 25 mg, or 50 mg capsule, or 150 mg tablet, administered by mouth.

Placebo

Intervention Type: DRUG

Matching placebo to uprifosbuvir capsule administered by mouth.

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

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.

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Uprifosbuvir 5 mg, 25 mg, or 50 mg capsule, or 150 mg tablet, administered by mouth.

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

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.

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Uprifosbuvir 5 mg, 25 mg, or 50 mg capsule, or 150 mg tablet, administered by mouth.

Placebo

Intervention Type: DRUG

Matching placebo to uprifosbuvir capsule administered by mouth.

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

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.

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Uprifosbuvir 5 mg, 25 mg, or 50 mg capsule, or 150 mg tablet, administered by mouth.

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

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.

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Uprifosbuvir 5 mg, 25 mg, or 50 mg capsule, or 150 mg tablet, administered by mouth.

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

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.

Group Type: EXPERIMENTAL

Itraconazole

Intervention Type: DRUG

Itraconazole is supplied as 10 mg/mL oral solution or 100 mg capsules administered by mouth.

Interventions

Uprifosbuvir

Uprifosbuvir 5 mg, 25 mg, or 50 mg capsule, or 150 mg tablet, administered by mouth.

Intervention Type: DRUG

Placebo

Matching placebo to uprifosbuvir capsule administered by mouth.

Intervention Type: DRUG

Itraconazole

Itraconazole is supplied as 10 mg/mL oral solution or 100 mg capsules administered by mouth.

Intervention Type: DRUG

Other Intervention Names

MK-3682/IDX21437; Sporanox®

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Other Identifiers

U1111-1149-5611

Identifier Type: OTHER

Identifier Source: secondary_id

IDX-04B-001

Identifier Type: OTHER

Identifier Source: secondary_id

2013-004043-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-3682-001

Identifier Type: OTHER

Identifier Source: secondary_id

3682-001

Identifier Type: -

Identifier Source: org_study_id