A Drug-Drug Interaction Study Evaluating the Combination of IDX320 and IDX184 in Healthy Participants (MK-6844-002)

A Phase I, Double-Blind, Multiple-Dose Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between IDX320 and IDX184 in Healthy Subjects

This study is designed to evaluate the potential for a pharmacokinetic (PK) drug-drug interaction between IDX320 and IDX184 and to assess the safety and tolerability when the two drugs are administered in combination in healthy participants.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: IDX320; Drug: IDX184; Drug: IDX184 placebo; Drug: IDX320 placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

To participate in the study, participants must meet the following requirements:

1. Must be a healthy male or female between 19 and 65 years of age with body mass index (BMI) between 18 and 35 kg/m2.
2. Must be a non-smoker.
3. Must agree to use an acceptable double-barrier method of birth control.
4. Must provide written informed consent after the study has been fully explained.

Exclusion Criteria:

Participants are not eligible if they meet any of the following:

1. Pregnant or breastfeeding.
2. History of clinically significant diseases, as determined by the investigator.
3. Safety laboratory abnormalities at screening which are clinically significant.
4. Positive screening test for hepatitis B virus, hepatitis C virus or human immunodeficiency virus (HIV).
5. Use of chronic prescription medications within 3 months, acute prescription medications within 14 days, or systemic over-the-counter (OTC) medications within 7 days of the starting the study.
6. Current abuse of alcohol or illicit drugs, or history of alcohol or illicit drug abuse within the preceding two years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IDX320 + PBO → IDX320 + IDX184; 400 mg IDX320 and IDX184 matching placebo (PBO) once daily for 7 days; followed by 400 mg IDX320 and 100 mg IDX184 once daily for 7 days	Drug: IDX320; IDX320 400 mg in tablets (8x50 mg) administered orally once daily; Drug: IDX184; IDX184 100 mg in capsules (2x50 mg) administered orally once daily; Drug: IDX184 placebo; IDX184 matching placebo in capsules administered orally once daily
Experimental: IDX184 + PBO → IDX184 + IDX320; 100 mg IDX184 and IDX320 matching PBO for 7 days; followed by 100 mg IDX184 and 400 mg IDX320 for 7 days	Drug: IDX320; IDX320 400 mg in tablets (8x50 mg) administered orally once daily; Drug: IDX184; IDX184 100 mg in capsules (2x50 mg) administered orally once daily; Drug: IDX320 placebo; IDX320 matching placebo in tablets administered orally once daily
Placebo Comparator: IDX320 PBO + IDX184 PBO; IDX320 matching PBO + IDX184 matching PBO for 14 days	Drug: IDX184 placebo; IDX184 matching placebo in capsules administered orally once daily; Drug: IDX320 placebo; IDX320 matching placebo in tablets administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the curve at steady state (AUCss) of plasma IDX320	Days 1-7 pre-dose; Day 7: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 hrs postdose; Days 8-14 pre-dose; Day 14: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hrs postdose
AUCss of plasma IDX184	Days 1-7 pre-dose; Day 7: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 hrs postdose; Days 8-14 pre-dose; Day 14: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hrs postdose
AUCss of plasma 2'-methylguanosine (2'-MeG)	Days 1-7 pre-dose; Day 7: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 hrs postdose; Days 8-14 pre-dose; Day 14: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hrs postdose
Maximum observed concentration (Cmax) of plasma IDX320	Days 1-7 pre-dose; Day 7: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 hrs postdose; Days 8-14 pre-dose; Day 14: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hrs postdose
Cmax of plasma IDX184	Days 1-7 pre-dose; Day 7: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 hrs postdose; Days 8-14 pre-dose; Day 14: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hrs postdose
Cmax of plasma 2'-MeG	Days 1-7 pre-dose; Day 7: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 hrs postdose; Days 8-14 pre-dose; Day 14: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hrs postdose
Trough concentration (Ctrough) of plasma IDX320	Days 1-7 pre-dose; Day 7: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 hrs postdose; Days 8-14 pre-dose; Day 14: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hrs postdose
Ctrough of plasma IDX184	Days 1-7 pre-dose; Day 7: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 hrs postdose; Days 8-14 pre-dose; Day 14: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hrs postdose
Ctrough of plasma 2"-MeG	Days 1-7 pre-dose; Day 7: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 hrs postdose; Days 8-14 pre-dose; Day 14: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hrs postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with an adverse event (AE)	Up to Day 19
Number of participants who discontinued treatment due to an AE	Up to Day 14

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: July 2, 2010
• First Submitted That Met QC Criteria: July 2, 2010
• First Posted (Estimate): July 5, 2010

Study Record Updates

• Last Update Posted (Estimate): January 22, 2016
• Last Update Submitted That Met QC Criteria: January 20, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: HCV; Hepatitis C
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: 6844-002; IDX-07A-002 (Other Identifier: Idenix)