Clinical trial NCT01532973: Safety, Pharmacokinetics and Pharmacodynamics of Elbasvir (MK-8742) in Hepatitis C Infected Males (MK-8742-002)
Official title: A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8742 in Hepatitis C Infected Males
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis, Viral, Human
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-02-15
Enrollment: 48
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Mean Reduction From Baseline in Log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 5 - HCV GT1
timeFrame: Baseline (Predose on Day 1) and 24-hour post-dose on Day 5
measure: Mean Reduction From Baseline in Log10 Plasma HCV RNA at Day 5 - HCV GT3
timeFrame: Baseline (Predose on Day 1) and 24-hour post-dose on Day 5
measure: Mean Reduction From Baseline in Log10 Plasma HCV RNA at Day 5 - HCV GT1a
timeFrame: Baseline (Predose on Day 1) and 24-hour post-dose on Day 5
measure: Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT1
timeFrame: Up to 5 days
measure: Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT3
timeFrame: Up to 5 days
measure: Mean Maximum Reduction in Log10 HCV Viral Load - HCV GT1a
timeFrame: Up to 5 days
measure: Number of Participants Experiencing an Adverse Event (AE) - Day 1 to Day 5
timeFrame: Up to 5 days
measure: Number of Participants Who Had Study Drug Discontinued Due to an Adverse Event
timeFrame: Up to 5 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Yeh 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.