Safety, Pharmacokinetics and Pharmacodynamics of Elbasvir (MK-8742) in Hepatitis C Infected Males (MK-8742-002)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hepatitis, Viral, Human

Treatments: Drug: Placebo; Drug: Elbasvir

Study type: Interventional

Funder types: Industry

Identifiers

NCT01532973

2011-005190-23 (EudraCT Number)

8742-002

Details and patient eligibility

About

The purpose of this study is to assess the safety, pharmacokinetics (PK) and pharmacodynamics of elbasvir (MK-8742) in Hepatitis C Virus (HCV)-infected participants. There will be 3 parts to this study; Part I will enroll only genotype (GT) 1 HCV-infected participants, Part II will enroll GT3 HCV-infected participants, and Part III will enroll only GT1a HCV-infected participants. All parts may run concurrently, or Parts II and III may be staggered.

Hypothesis (Part I): At a once-daily dose that is sufficiently safe and well tolerated in HCV-infected participants, elbasvir administered for 5 consecutive days has superior antiviral activity in GT1 HCV-infected participants compared to placebo, as measured by change from baseline in plasma HCV ribonucleic acid (RNA; log 10 copies/mL) at Day 5, 24-hour postdose timepoint. (a true mean viral RNA reduction of at least 3 log10 is anticipated).

Hypothesis (Part II): At a dose that is sufficiently safe in GT3 HCV-infected participants, the mean maximum reduction in HCV viral load is greater following multiple dose oral administration of elbasvir as compared to placebo.

Hypothesis (Part III): At a once-daily dose that is sufficiently safe and well tolerated in HCV-infected participants, elbasvir administered for 5 consecutive days has superior antiviral activity in GT1a HCV-infected participants compared to placebo, as measured by change from baseline in plasma HCV RNA (log 10 copies/mL) at Day 5, 24-hour postdose timepoint. (a true mean viral RNA reduction of at least 3 log10 is anticipated).

Enrollment: 48 patients

Sex: Male

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Body Mass Index (BMI) of 18 to ≤ 37 kg/m^2
• Clinical diagnosis of chronic HCV infection defined by positive serology for HCV for at least 6 months and detectable HCV RNA in peripheral blood ≥105 IU/mL at screening
• Participant must be infected with HCV GT1a, GT1b, or GT 3

Exclusion criteria

• Co-infection with GT1 and GT3
• Estimated creatinine clearance of ≤70 mL/min based on the Cockcroft-Gault equation
• History of stroke, chronic seizures, or major neurological disorder
• History of clinically significant endocrine, gastrointestinal (excepting HCV infection), cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• History of neoplastic disease
• Positive Hepatitis B surface antigen at the pre-study (screening) visit
• Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior to the prestudy (screening) visit.
• Previous treatments (s) with nonstructural protein 5A (NS5A) inhibitors
• <4 weeks since administration of any experimental protease inhibitor
• Previous exposure to interferon-alpha and/or ribavirin within 3 month prior to the first dose of elbasvir in the study
• Clinical or laboratory evidence of advanced or decompensated liver disease

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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48 participants in 10 patient groups

GT1 HCV 10-mg Elbasvir (Panel A)

Experimental group

Description:

Participants with GT1 HCV receive 10 -mg elbasvir or matching placebo for 5 consecutive days during Part I of the study.

Treatment:

Drug: Elbasvir

Drug: Placebo

GTI HCV 50-g Elbasvir (Panel B)

Experimental group

Description:

Participants with GT1 HCV receive 50-mg elbasvir or matching placebo for 5 consecutive days during Part I of the study.

Treatment:

Drug: Elbasvir

Drug: Placebo

GT1 HCV 5-mg Elbavir (Panel C)

Experimental group

Description:

Participants with GT1 HCV receive 5-mg elbasvir or matching placebo for 5 consecutive days during Part I of the study.

Treatment:

Drug: Elbasvir

Drug: Placebo

GT1 HCV 200-mg Elbasvir (Panel D)

Experimental group

Description:

Participants with GT1 HCV receive 200-mg elbasvir or matching placebo for 5 consecutive days during Part I of the study.

Treatment:

Drug: Elbasvir

Drug: Placebo

GT3 HCV 10-mg Elbasvir (Panel E)

Experimental group

Description:

Participants with GT3 HCV receive 10-mg elbasvir or matching placebo for 5 consecutive days during Part II of the study.

Treatment:

Drug: Elbasvir

Drug: Placebo

GT3 HCV 50-mg Elbasvir (Panel F)

Experimental group

Description:

Participants with GT3 HCV receive 50-mg elbasvir or matching placebo for 5 consecutive days during Part II of the study.

Treatment:

Drug: Elbasvir

Drug: Placebo

GT3 HCV 100-mg Elbasvir (Panel G)

Experimental group

Description:

Participants with GT3 HCV receive 100-mg elbasvir or matching placebo for 5 consecutive days during Part II of the study.

Treatment:

Drug: Elbasvir

Drug: Placebo

GT3 HCV 200-mg Elbasvir (Panel H)

Experimental group

Description:

Participants with GT3 HCV receive 200-mg elbasvir or matching placebo for 5 consecutive days during Part II of the study.

Treatment:

Drug: Elbasvir

Drug: Placebo

GT1a HCV 10-mg Elbasvir (Panel I)

Experimental group

Description:

Participants with GT1a only HCV receive 10-mg elbasvir or matching placebo for 5 consecutive days during Part III of the study.

Treatment:

Drug: Elbasvir

Drug: Placebo

GT1a HCV 50-mg Elbasvir (Panel J)

Experimental group

Description:

Participants with GT1a only HCV receive 50-mg elbasvir or matching placebo for 5 consecutive days during Part III of the study.

Treatment:

Drug: Elbasvir

Drug: Placebo