Samatasvir (IDX719) in Combinations With Simeprevir and/or TMC647055/Ritonavir With or Without Ribavirin for 12 Weeks in Participants With Chronic Hepatitis C Infection (MK-1894-005)
Phase 2
Completed
- Conditions
- Chronic Hepatitis C Virus
- Interventions
- Biological: Pegylated interferon (Peg-IFN)Other: Samatasvir matching placebo
- Registration Number
- NCT01852604
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Parts A and B of this study are designed to evaluate the safety, tolerability, efficacy and pharmacokinetic profiles of samatasvir and simeprevir when administered in combination with ribavirin (RBV) for 12 weeks in treatment-naïve, Genotype (GT) 1b, 4 and 6 hepatitic C virus (HCV)-infected participants.
Part C of this study is designed to evaluate the safety, tolerability, efficacy and pharmacokinetic profiles of samatasvir, simeprevir, TMC647055 and ritonavir (RTV) when administered in combination with or without RBV for 12 weeks in treatment-naïve or interferon/RBV-treatment relapsed, GT 1a and 1b HCV-infected participants.
- Detailed Description
Part A of this study is randomized and double-blind. Parts B and C are randomized and open-label.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 143
Inclusion Criteria
- Must have Genotype 1a, 1b, 4 or 6 HCV infection.
- Documented clinical history compatible with chronic hepatitis C
- HCV treatment-naïve or interferon/RBV-treatment relapsed (Part C)
- Must agree to use an acceptable double method of birth control (one of which must be a barrier method) for at least 6 months after the last dose of study drugs.
Exclusion Criteria
- Female participants who are pregnant or breastfeeding.
- Body Mass Index (BMI) > 36 kg/m2.
- Co-infected with hepatitis B virus or human immunodeficiency virus (HIV).
- History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC.
- History or signs of decompensated liver disease: ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency.
- Has one or more known primary or secondary causes of liver disease, other than hepatitis C
- History of, or active, acute or chronic, liver or biliary injury due to drugs, toxins, non-HCV viral hepatitis, gallstones or other etiologies
- Donated blood or had significant blood loss 30 days prior to dosing
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV Ritonavir (RTV) Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily plus RTV 30 mg once daily for 12 weeks Part A: GT 1b, 4 - samatasvir 150/simeprevir/RBV Ribavirin (RBV) Part A: Participants with genotype 1b or 4 received samatasvir 150 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV Ribavirin (RBV) Part A: Participants with genotype 1b or 4 received samatasvir 50 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV Ribavirin (RBV) Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily plus RTV 30 mg once daily for 12 weeks Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV Pegylated interferon (Peg-IFN) Part A: Participants with genotype 1b or 4 received samatasvir 50 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV Samatasvir matching placebo Part A: Participants with genotype 1b or 4 received samatasvir 100 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV Ribavirin (RBV) Part A: Participants with genotype 1b or 4 received samatasvir 100 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV Samatasvir matching placebo Part A: Participants with genotype 1b or 4 received samatasvir 50 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV Pegylated interferon (Peg-IFN) Part A: Participants with genotype 1b or 4 received samatasvir 100 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 150/simeprevir/RBV Pegylated interferon (Peg-IFN) Part A: Participants with genotype 1b or 4 received samatasvir 150 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 1b, 4 - samatasvir 100/simeprevir/RBV Ribavirin (RBV) Part B: Participants with genotype 1b or 4 received samatasvir 100 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 6 - samatasvir 100/simeprevir/RBV Ribavirin (RBV) Part B: Participants with Genotype 6 received samatasvir 100 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV Pegylated interferon (Peg-IFN) Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily plus RTV 30 mg once daily for 12 weeks Part B: GT 1b, 4 - samatasvir 25/simeprevir/RBV Pegylated interferon (Peg-IFN) Part B: Participants with genotype 1b or 4 received samatasvir 25 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV Ribavirin (RBV) Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily, plus RTV 30 mg once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV Ritonavir (RTV) Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily, plus RTV 30 mg once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 1b, 4 - samatasvir 25/simeprevir/RBV Ribavirin (RBV) Part B: Participants with genotype 1b or 4 received samatasvir 25 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 1b, 4 - samatasvir 100/simeprevir/RBV Pegylated interferon (Peg-IFN) Part B: Participants with genotype 1b or 4 received samatasvir 100 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 6 - samatasvir 100/simeprevir/RBV Pegylated interferon (Peg-IFN) Part B: Participants with Genotype 6 received samatasvir 100 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV Pegylated interferon (Peg-IFN) Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily, plus RTV 30 mg once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV TMC647055 Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily plus RTV 30 mg once daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV TMC647055 Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily, plus RTV 30 mg once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV Simeprevir Part A: Participants with genotype 1b or 4 received samatasvir 50 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV Simeprevir Part A: Participants with genotype 1b or 4 received samatasvir 100 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 150/simeprevir/RBV Simeprevir Part A: Participants with genotype 1b or 4 received samatasvir 150 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 150/simeprevir/RBV Samatasvir Part A: Participants with genotype 1b or 4 received samatasvir 150 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 1b, 4 - samatasvir 25/simeprevir/RBV Simeprevir Part B: Participants with genotype 1b or 4 received samatasvir 25 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 1b, 4 - samatasvir 100/simeprevir/RBV Simeprevir Part B: Participants with genotype 1b or 4 received samatasvir 100 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 6 - samatasvir 100/simeprevir/RBV Simeprevir Part B: Participants with Genotype 6 received samatasvir 100 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV Simeprevir Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily plus RTV 30 mg once daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV Simeprevir Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily, plus RTV 30 mg once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV Samatasvir Part A: Participants with genotype 1b or 4 received samatasvir 50 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV Samatasvir Part A: Participants with genotype 1b or 4 received samatasvir 100 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 1b, 4 - samatasvir 25/simeprevir/RBV Samatasvir Part B: Participants with genotype 1b or 4 received samatasvir 25 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 1b, 4 - samatasvir 100/simeprevir/RBV Samatasvir Part B: Participants with genotype 1b or 4 received samatasvir 100 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part B: GT 6 - samatasvir 100/simeprevir/RBV Samatasvir Part B: Participants with Genotype 6 received samatasvir 100 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV Samatasvir Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily plus RTV 30 mg once daily for 12 weeks Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV Samatasvir Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily, plus RTV 30 mg once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks
- Primary Outcome Measures
Name Time Method Percentage of participants who experienced an adverse event (AE) Up to approximately 95 weeks Percentage of participants who experienced a serious adverse event (SAE) Up to approximately 95 weeks Percentage of participants who experienced a Grade 1-4 laboratory abnormality Up to 66 weeks Percentage of participants who experienced sustained virologic response 4 weeks after the end of treatment (SVR4) Up to 16 weeks
- Secondary Outcome Measures
Name Time Method Percentage of participants who experienced rapid virologic response (RVR) Week 4 Percentage of participants who experienced early virologic response (EVR) Week 12 Percentage of participants who experienced sustained virologic response 8 weeks after the end of treatment (SVR8) Up to 20 weeks Percentage of participants who experienced sustained virologic response 12 weeks after the end of treatment (SVR12) Up to 24 weeks Percentage of participants who experienced sustained virologic response 24 weeks after the end of treatment (SVR24) Up to 36 weeks Pharmacokinetic Parameter:Area under the concentration-time curve from time zero to t Days 1, 4, 7, 10, 14, 21, 28, 42, 56 and 84 Pharmacokinetic Parameter: Maximum observed drug concentration (Cmax) Days 1, 4, 7, 10, 14, 21, 28, 42, 56 and 84 Pharmacokinetic Parameter: Trough drug concentration (Ctrough) Days 1, 4, 7, 10, 14, 21, 28, 42, 56 and 84