Safety, Pharmacokinetics and Pharmacodynamics of Elbasvir (MK-8742) in Hepatitis C Infected Males (MK-8742-002)
A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8742 in Hepatitis C Infected Males
2 other identifiers
interventional
48
0 countries
N/A
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2012
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 10, 2012
CompletedFirst Posted
Study publicly available on registry
February 15, 2012
CompletedStudy Start
First participant enrolled
February 16, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 17, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
May 17, 2013
CompletedResults Posted
Study results publicly available
November 23, 2016
CompletedJuly 17, 2018
June 1, 2018
1.2 years
February 10, 2012
October 3, 2016
June 19, 2018
Conditions
Outcome Measures
Primary Outcomes (8)
Mean Reduction From Baseline in Log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 5 - HCV GT1
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.
Baseline (Predose on Day 1) and 24-hour post-dose on Day 5
Mean Reduction From Baseline in Log10 Plasma HCV RNA at Day 5 - HCV GT3
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
Baseline (Predose on Day 1) and 24-hour post-dose on Day 5
Mean Reduction From Baseline in Log10 Plasma HCV RNA at Day 5 - HCV GT1a
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.
Baseline (Predose on Day 1) and 24-hour post-dose on Day 5
Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT1
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.
Up to 5 days
Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT3
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.
Up to 5 days
Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT1a
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.
Up to 5 days
Number of Participants Experiencing an Adverse Event (AE) - Day 1 to Day 5
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.
Up to 5 days
Number of Participants Who Had Study Drug Discontinued Due to an Adverse Event
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.
Up to 5 days
Study Arms (10)
GT1 HCV 10-mg Elbasvir (Panel A)
EXPERIMENTALParticipants with GT1 HCV receive 10 -mg elbasvir or matching placebo for 5 consecutive days during Part I of the study.
GTI HCV 50-g Elbasvir (Panel B)
EXPERIMENTALParticipants with GT1 HCV receive 50-mg elbasvir or matching placebo for 5 consecutive days during Part I of the study.
GT1 HCV 5-mg Elbavir (Panel C)
EXPERIMENTALParticipants with GT1 HCV receive 5-mg elbasvir or matching placebo for 5 consecutive days during Part I of the study.
GT1 HCV 200-mg Elbasvir (Panel D)
EXPERIMENTALParticipants with GT1 HCV receive 200-mg elbasvir or matching placebo for 5 consecutive days during Part I of the study.
GT3 HCV 10-mg Elbasvir (Panel E)
EXPERIMENTALParticipants with GT3 HCV receive 10-mg elbasvir or matching placebo for 5 consecutive days during Part II of the study.
GT3 HCV 50-mg Elbasvir (Panel F)
EXPERIMENTALParticipants with GT3 HCV receive 50-mg elbasvir or matching placebo for 5 consecutive days during Part II of the study.
GT3 HCV 100-mg Elbasvir (Panel G)
EXPERIMENTALParticipants with GT3 HCV receive 100-mg elbasvir or matching placebo for 5 consecutive days during Part II of the study.
GT3 HCV 200-mg Elbasvir (Panel H)
EXPERIMENTALParticipants with GT3 HCV receive 200-mg elbasvir or matching placebo for 5 consecutive days during Part II of the study.
GT1a HCV 10-mg Elbasvir (Panel I)
EXPERIMENTALParticipants with GT1a only HCV receive 10-mg elbasvir or matching placebo for 5 consecutive days during Part III of the study.
GT1a HCV 50-mg Elbasvir (Panel J)
EXPERIMENTALParticipants with GT1a only HCV receive 50-mg elbasvir or matching placebo for 5 consecutive days during Part III of the study.
Interventions
Elbasvir was administered orally by tablet(s)
Dose-matched placebo tablets were administered orally.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (2)
Liu R, Curry S, McMonagle P, Yeh WW, Ludmerer SW, Jumes PA, Marshall WL, Kong S, Ingravallo P, Black S, Pak I, DiNubile MJ, Howe AY. Susceptibilities of genotype 1a, 1b, and 3 hepatitis C virus variants to the NS5A inhibitor elbasvir. Antimicrob Agents Chemother. 2015 Nov;59(11):6922-9. doi: 10.1128/AAC.01390-15. Epub 2015 Aug 24.
PMID: 26303801BACKGROUNDYeh WW, Fraser IP, Jumes P, Petry A, Lepeleire I, Robberechts M, Reitmann C, Van Dyck K, Huang X, Guo Z, Panebianco D, Nachbar RB, O'Mara E, Wagner JA, Butterton JR, Dutko FJ, Moiseev V, Kobalava Z, Huser A, Visan S, Schwabe C, Gane E, Popa S, Ghicavii N, Uhle M, Wagner F. Antiviral Activity, Safety, and Tolerability of Multiple Ascending Doses of Elbasvir or Grazoprevir in Participants Infected With Hepatitis C Virus Genotype-1 or -3. Clin Ther. 2018 May;40(5):704-718.e6. doi: 10.1016/j.clinthera.2018.03.002. Epub 2018 Apr 25.
PMID: 29703432RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Vice President, Global Clinical Development
- Organization
- Merck, Sharp & Dohme Corp.
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 10, 2012
First Posted
February 15, 2012
Study Start
February 16, 2012
Primary Completion
May 17, 2013
Study Completion
May 17, 2013
Last Updated
July 17, 2018
Results First Posted
November 23, 2016
Record last verified: 2018-06