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Completed

NCT Number: NCT01532973

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

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).

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Key information

Conditions

Hepatitis, Viral, Human Digestive System Diseases Hepatitis Infections Liver Diseases Virus Diseases

Age range

18 year–60 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Elbasvir

Drug

Elbasvir was administered orally by tablet(s)

Placebo

Drug

Dose-matched placebo tablets were administered orally.

Primary outcomes

  1. Mean Reduction From Baseline in Log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 5 - HCV GT1

    Time frame: Baseline (Predose on Day 1) and 24-hour post-dose on Day 5

    HCV RNA levels were assessed at baseline (predose on Day 1) and 24 hours postdose on Day 5 using the Roche TaqMan HCV 2.0 assay and transformed to Log10 values. The lower limits of quantification (LLOQ) and detection (LLD) were 25 and 9.3 IU/mL, respectively. Least squares means and confidence intervals obtained from the linear mixed model with log10 HCV RNA reduction as response and a fixed effect for treatment, time and treatment by time interaction.

  2. Mean Reduction From Baseline in Log10 Plasma HCV RNA at Day 5 - HCV GT3

    Time frame: Baseline (Predose on Day 1) and 24-hour post-dose on Day 5

    HCV RNA levels were assessed at baseline (predose on Day 1) and 24 hours postdose on Day 5 using the Roche TaqMan HCV 2.0 assay and transformed to Log10 values. The lower limits of quantification (LLOQ) and detection (LLD) were 25 and 9.3 IU/mL, respectively. Least squares means and confidence intervals obtained from the linear mixed model with log10 HCV RNA reduction as response and a fixed effect for treatment, time and treatment by time interaction

  3. Mean Reduction From Baseline in Log10 Plasma HCV RNA at Day 5 - HCV GT1a

    Time frame: Baseline (Predose on Day 1) and 24-hour post-dose on Day 5

    HCV RNA levels were assessed at baseline (predose on Day 1) and 24 hours postdose on Day 5 using the Roche TaqMan HCV 2.0 assay and transformed to Log10 values. The lower limits of quantification (LLOQ) and detection (LLD) were 25 and 9.3 IU/mL, respectively. Least squares means and confidence intervals obtained from the linear mixed model with log10 HCV RNA reduction as response and a fixed effect for treatment, time and treatment by time interaction.

  4. Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT1

    Time frame: Up to 5 days

    HCV RNA levels were assessed at baseline (predose Day 1) and 24 hours postdose on Days 1-5. using the Roche TaqMan HCV 2.0 assay and transformed to Log10 values. The lower limits of quantification (LLOQ) and detection (LLD) were 25 and 9.3 IU/mL, respectively. The change in log10 LS mean HCV RNA levels was calculated for each timepoint and the maximum change from baseline was recorded.

  5. Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT3

    Time frame: Up to 5 days

    HCV RNA levels were assessed at baseline (predose Day 1) and 24 hours postdose on Days 1-5. using the Roche TaqMan HCV 2.0 assay and transformed to Log10 values. The lower limits of quantification (LLOQ) and detection (LLD) were 25 and 9.3 IU/mL, respectively. The change in log10 LS mean HCV RNA levels was calculated for each timepoint and the maximum change from baseline was recorded.

  6. Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT1a

    Time frame: Up to 5 days

    HCV RNA levels were assessed at baseline (predose Day 1) and 24 hours postdose on Days 1-5. using the Roche TaqMan HCV 2.0 assay and transformed to Log10 values. The lower limits of quantification (LLOQ) and detection (LLD) were 25 and 9.3 IU/mL, respectively. The change in log10 LS mean HCV RNA levels was calculated for each timepoint and the maximum change from baseline was recorded.

  7. Number of Participants Experiencing an Adverse Event (AE) - Day 1 to Day 5

    Time frame: Up to 5 days

    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE.

  8. Number of Participants Who Had Study Drug Discontinued Due to an Adverse Event

    Time frame: Up to 5 days

    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. Participants who had study drug discontinued due to an AE were recorded.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8742 in Hepatitis C Infected Males

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
Feb 15, 2012
Registry last updated
Jul 17, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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