Safety and Antiviral Activity of IDX184 in Combination With Pegylated Interferon and Ribavirin (MK-2355-004)
Phase 2
Completed
- Conditions
- Chronic Hepatitis C Infection
- Interventions
- Registration Number
- NCT01011166
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study will assess short term safety, antiviral activity and pharmacokinetics (PK) of IDX184 in combination with Peg-interferon (Peg-IFN)/Ribavirin (RBV) in participants with hepatitis C virus (HCV) genotype (GT) 1 infection. These data will guide dose selection for future, longer term studies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 81
Inclusion Criteria
- Has documented chronic HCV GT1 infection
- Agrees to use of double-barrier contraception and males agree not to donate sperm from the first dose of study therapy through at least 6 months after the final dose of study therapy
Exclusion Criteria
- Has received previous antiviral treatment for HCV infection
- Has cirrhosis or decompensated liver disease
- Is pregnant or breastfeeding
- Is co-infected with hepatitis B virus (e.g., hepatitis B surface antigen [HBsAg] positive) and/or human immunodeficiency virus (HIV)
- Has clinically significant concomitant disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description IDX184 100 mg BID + Peg-IFN/RBV Ribavirin (RBV) Participants randomized 4:1 (active:placebo) to receive IDX184 100 mg or placebo twice daily (BID) in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV alone on Days 14-28. IDX184 50 mg QD + Peg-IFN/RBV Placebo Participants randomized 4:1 (active:placebo) to receive IDX184 50 mg or placebo once daily (QD) in combination with Peg-IFN/RBV on Days 14-28 and Peg-IFN/RBV on Days 14-28. IDX184 100 mg QD + Peg-IFN/RBV Ribavirin (RBV) Participants randomized 4:1 (active:placebo) to receive IDX184 50 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV alone on Days 14-28. IDX184 200 mg QD + Peg-IFN/RBV Peginterferon alfa-2a (Peg-IFN) Participants randomized 4:1 (active:placebo) to receive IDX184 100 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 50 mg QD + Peg-IFN/RBV Peginterferon alfa-2a (Peg-IFN) Participants randomized 4:1 (active:placebo) to receive IDX184 50 mg or placebo once daily (QD) in combination with Peg-IFN/RBV on Days 14-28 and Peg-IFN/RBV on Days 14-28. IDX184 100 mg BID + Peg-IFN/RBV Placebo Participants randomized 4:1 (active:placebo) to receive IDX184 100 mg or placebo twice daily (BID) in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV alone on Days 14-28. IDX184 100 mg QD + Peg-IFN/RBV Placebo Participants randomized 4:1 (active:placebo) to receive IDX184 50 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV alone on Days 14-28. IDX184 100 mg BID + Peg-IFN/RBV IDX184 Participants randomized 4:1 (active:placebo) to receive IDX184 100 mg or placebo twice daily (BID) in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV alone on Days 14-28. IDX184 100 mg BID + Peg-IFN/RBV Peginterferon alfa-2a (Peg-IFN) Participants randomized 4:1 (active:placebo) to receive IDX184 100 mg or placebo twice daily (BID) in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV alone on Days 14-28. IDX184 150 mg QD + Peg-IFN/RBV Ribavirin (RBV) Participants randomized 4:1 (active:placebo) to receive IDX184 150 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 200 mg QD + Peg-IFN/RBV IDX184 Participants randomized 4:1 (active:placebo) to receive IDX184 100 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 200 mg QD + Peg-IFN/RBV Ribavirin (RBV) Participants randomized 4:1 (active:placebo) to receive IDX184 100 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 150 mg QD + Peg-IFN/RBV Peginterferon alfa-2a (Peg-IFN) Participants randomized 4:1 (active:placebo) to receive IDX184 150 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 200 mg BID + Peg-IFN/RBV IDX184 Participants randomized 4:1 (active:placebo) to receive IDX184 200 mg or placebo BID in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 200 mg BID + Peg-IFN/RBV Placebo Participants randomized 4:1 (active:placebo) to receive IDX184 200 mg or placebo BID in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 50 mg QD + Peg-IFN/RBV IDX184 Participants randomized 4:1 (active:placebo) to receive IDX184 50 mg or placebo once daily (QD) in combination with Peg-IFN/RBV on Days 14-28 and Peg-IFN/RBV on Days 14-28. IDX184 50 mg QD + Peg-IFN/RBV Ribavirin (RBV) Participants randomized 4:1 (active:placebo) to receive IDX184 50 mg or placebo once daily (QD) in combination with Peg-IFN/RBV on Days 14-28 and Peg-IFN/RBV on Days 14-28. IDX184 100 mg QD + Peg-IFN/RBV IDX184 Participants randomized 4:1 (active:placebo) to receive IDX184 50 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV alone on Days 14-28. IDX184 100 mg QD + Peg-IFN/RBV Peginterferon alfa-2a (Peg-IFN) Participants randomized 4:1 (active:placebo) to receive IDX184 50 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV alone on Days 14-28. IDX184 150 mg QD + Peg-IFN/RBV IDX184 Participants randomized 4:1 (active:placebo) to receive IDX184 150 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 150 mg QD + Peg-IFN/RBV Placebo Participants randomized 4:1 (active:placebo) to receive IDX184 150 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 200 mg QD + Peg-IFN/RBV Placebo Participants randomized 4:1 (active:placebo) to receive IDX184 100 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 200 mg BID + Peg-IFN/RBV Peginterferon alfa-2a (Peg-IFN) Participants randomized 4:1 (active:placebo) to receive IDX184 200 mg or placebo BID in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. IDX184 200 mg BID + Peg-IFN/RBV Ribavirin (RBV) Participants randomized 4:1 (active:placebo) to receive IDX184 200 mg or placebo BID in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28.
- Primary Outcome Measures
Name Time Method Change in HCV ribonucleic acid (RNA) level from Baseline to Day 15 Baseline and Day 15 Percentage of participants experiencing dose-limiting toxicities (DLTs) Up to 28 days Percentage of participants experiencing adverse events (AEs) Up to 28 days Percentage of participants experiencing Grade 1-4 laboratory abnormalities Up to 28 days Percentage of participants experiencing serious adverse events (SAEs) Up to 28 days
- Secondary Outcome Measures
Name Time Method Time to maximum concentration (Tmax) Up to 28 days Trough concentration (Ctrough) Up to 28 days Maximum concentration (Cmax) Up to 28 days Change in alanine aminotransferase (ALT) level from Baseline to Day 15 Baseline and Day 15 Observed terminal half-life (Thalf) Up to 28 days Change in HCV RNA level from Baseline to Day 28 Baseline and Day 28 Percentage of participants with undetectable HCV RNA at Day 15 Day 15 Change in ALT level from Baseline to Day 28 Baseline and Day 28 Area under the drug concentration-time curve (AUC) from time 0 to last measurable concentration (AUC0-t) Up to 28 days AUC from time zero to infinity (AUC0-~) Up to 28 days Percentage of participants with undetectable HCV RNA at Day 28 Day 28 Percentage of participants experiencing virologic breakthrough while on study therapy Up to 28 days