Phase 1
Completed N=18
Safety, Pharmacokinetics and Pharmacodynamics of Elbasvir (MK-8742) in Hepatitis C Infected Males (MK-8742-002)
Hepatitis, Viral, Human
Source: ClinicalTrials.gov NCT01532973 ↗
Enrolled (actual)
18
Serious AEs
0.0%
Results posted
Nov 2016
Primary outcomePrimary: Mean Reduction From Baseline in Log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 5 - HCV GT1 — 4.25; 4.40; 3.56; 0.00 IU/mL
Summary
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Reduction From Baseline in Log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 5 - HCV GT1 |
4.25; 4.40; 3.56; 0.00 | — |
| PRIMARY Mean Reduction From Baseline in Log10 Plasma HCV RNA at Day 5 - HCV GT3 |
1.01; 2.06; 2.72; 0.00 | — |
| PRIMARY Mean Reduction From Baseline in Log10 Plasma HCV RNA at Day 5 - HCV GT1a |
3.20; 3.95; 0.00 | — |
| PRIMARY Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT1 |
4.44; 5.21; 4.15; 0.54 | — |
| PRIMARY Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT3 |
1.27; 3.12; 3.38; 0.54 | — |
| PRIMARY Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT1a |
3.72; 4.17; 0.54 | — |
| PRIMARY Number of Participants Experiencing an Adverse Event (AE) - Day 1 to Day 5 |
4; 6; 7; 1; 4 | — |
| PRIMARY Number of Participants Who Had Study Drug Discontinued Due to an Adverse Event |
0; 0; 0; 0; 0 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01532973). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.