Clinical trial NCT02461563: A Multiple-Dose Study to Evaluate MK-1075 in Hepatitis C Virus (HCV) Infected Participants (MK-1075-004)
Official title: A Multiple-Dose Study to Evaluate the Safety, Pharmacodynamics and Pharmacokinetics of MK-1075 in GT3 and GT1 HCV Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C Virus Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-06-03
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate safety, pharmacokinetics (PK), and the ability of MK-1075 to suppress viral load (VL) in HCV-infected participants during 7 days of once daily dose administration. The primary hypothesis is at a once-daily dose that is sufficiently safe and well tolerated in HCV-infected participants, the mean maximum HCV RNA (log10 IU/mL) reduction is at least 3 log10 IU/mL as compared to baseline following multiple dose oral administration of MK-1075 in HCV genotype 1 (GT1) and genotype 3 (GT3) infected participants.


Eligibility criteria: Inclusion Criteria:

* Female of non-childbearing potential
* Have a body mass index (BMI) \>=18 to =\< 37 kg/m\^2
* Excepting HCV infection, be in good health
* Have a clinical diagnosis of chronic HCV infection, exclusively GT1 or exclusively GT3
* Agree to follow smoking restrictions

Exclusion Criteria:

* Has a history of clinically significant, not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or diseases.
* Have been treated with amiodarone within the prior year, or is currently on beta-blockers or verapamil
* Has a history of cancer (malignancy)
* Has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
* Is positive for hepatitis B surface antigen or human immunodeficiency virus (HIV)
* Has had major surgery, donated or lost approximately 500 mL blood within 4 weeks prior to screening visit
* Has participated in another drug trial within 4 weeks prior to screening visit
* Is taking a non-permitted medication to treat a co-morbid condition
* Consumes greater than 2 glasses of alcoholic beverages
* Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 12 months
* Has evidence or history of chronic hepatitis not caused by HCV, including but not limited to non-HCV viral hepatitis, non-alcoholic steatohepatitis (NASH), drug-induced hepatitis, or autoimmune hepatitis
* Has been treated with other HCV inhibitors, such as sofosbuvir or VX-135
* Has evidence of advanced or decompensated liver disease, bridging fibrosis or higher grade fibrosis from a prior liver biopsy

Primary outcomes:
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to Day 42
measure: Number of Participants Who Discontinued Treatment Due to an AE
timeFrame: Up to Day 7
measure: Change From Baseline in Maximum log10 HCV RNA Following Multiple Dose Oral Administration of MK-1075
timeFrame: Day 1 (pre-dose, 2, 4, 8, 12, and 24 hours postdose); Days 3, 4, 5, 6 (pre-dose); Day 7 (predose, 4, 12, 24, 48, 72, 96, 120, and 192 hours postdose); Days 21, 28 and 42
Secondary outcomes:
measure: Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hrs (AUC 0-24hr) of MK-1075 Following Multiple Dose Oral Administration of MK-1075
timeFrame: Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
measure: AUC 0-24hr of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075
timeFrame: Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
measure: Area Under the Plasma Concentration Time Curve From Time 0 to Last (AUC 0-last) of MK-1075 Following Multiple Dose Oral Administration of MK-1075
timeFrame: Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
measure: AUC 0-last of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075
timeFrame: Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
measure: Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-1075 Following Multiple Dose Oral Administration of MK-1075
timeFrame: Day 7 at 24 hours postdose
measure: C24hr of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075
timeFrame: Day 7 at 24 hours postdose
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: