A Multiple-Dose Study to Evaluate MK-1075 in Hepatitis C Virus (HCV) Infected Participants (MK-1075-004)

NCT02461563 | Completed Phase 1 Results

• 2 other identifiers: 1075-0042015-001687-18
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatitis C Virus Infection

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experienced an Adverse Event (AE)

  An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

  Up to Day 42

• Number of Participants Who Discontinued Treatment Due to an AE

  An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

  Up to Day 7

• Change From Baseline in Maximum log10 HCV RNA Following Multiple Dose Oral Administration of MK-1075

  Blood was collected on Days 1, 3, 4, 5, 6, 7, 21, 28 and 42, where baseline measurement was defined as the measurement obtained pre-dose on the first day of dosing. Change from baseline in log10 HCV RNA levels, was determined, and the maximum reduction in HCV RNA was analyzed by an ANOVA model with a fixed effect for treatment. The primary hypothesis is, with a posterior probability larger than 70%, there is at least a 3 log10 reduction from baseline in HCV RNA.

  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 (6)

• 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

  Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• AUC 0-24hr of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075

  Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• 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

  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

• AUC 0-last of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075

  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

• Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-1075 Following Multiple Dose Oral Administration of MK-1075

  Day 7 at 24 hours postdose

Study Arms (6)

GT1: 200 mg MK-1075

EXPERIMENTAL

Fasted GT1 participants are administered 200 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days

Drug: 200 mg MK-1075

GT1: 400 mg MK-1075

EXPERIMENTAL

Fasted GT1 participants are administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days

Drug: 400 mg MK-1075

GT1: 800 mg MK-1075

EXPERIMENTAL

Fasted GT1 participants are administered 800 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days

Drug: 800 mg MK-1075

GT3: 200 mg MK-1075

EXPERIMENTAL

Fasted GT3 participants are administered 200 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days

Drug: 200 mg MK-1075

GT3: 400 mg MK-1075

EXPERIMENTAL

Fasted GT3 participants are administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days

Drug: 400 mg MK-1075

GT3: 800 mg MK-1075

EXPERIMENTAL

Fasted GT3 participants are administered 800 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days

Drug: 800 mg MK-1075

Interventions

200 mg MK-1075 DRUG

Two 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days

GT1: 200 mg MK-1075; GT3: 200 mg MK-1075

400 mg MK-1075 DRUG

Four 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days

GT1: 400 mg MK-1075; GT3: 400 mg MK-1075

800 mg MK-1075 DRUG

Eight 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days

GT1: 800 mg MK-1075; GT3: 800 mg MK-1075

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2015
• First Posted: June 3, 2015
• Study Start: June 23, 2015
• Primary Completion: December 23, 2015
• Study Completion: December 23, 2015
• Last Updated: November 13, 2018
• Results First Posted: November 13, 2018

Record last verified: 2018-04