A Multiple Dose Study of MK-5172 in Hepatitis C-Infected Participants (MK-5172-010)

This study is currently recruiting participants.
Verified April 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01537900
First received: February 17, 2012
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

This study will compare hepatic pharmacokinetics (PK) derived from liver tissue to plasma PK after administration of MK-5172 to participants with chronic hepatitis C virus (HCV) infection. Participants will be randomized to one of four different liver ultrasound-guided Fine Needle Aspirate (FNA) schedules (at 4-, 8-, 24-, or 72-hours after the Day 7 dose).


Condition Intervention Phase
Hepatitis
Drug: MK-5172
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multiple Dose Study to Evaluate Pharmacokinetics and Hepatitis C Virus RNA Dynamics Following Administration of MK-5172 in Hepatitis C Infected Patients

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Area under the concentration versus time curve (AUC) for MK-5172 in the liver over 24 hours (AUC[H,0-24 hr]) [ Time Frame: Over 24 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
  • MK-5172 concentration in the liver at 4 hours post dose (C[H4hr]) [ Time Frame: 4 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
  • MK-5172 concentration in the liver at 8 hours post dose (C[H8hr]) [ Time Frame: 8 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
  • MK-5172 concentration in the liver at 24 hours post dose (C[H24hr]) [ Time Frame: 24 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
  • MK-5172 concentration in the liver at 72 hours post dose (C[H72hr]) [ Time Frame: 72 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
  • Apparent terminal half life (t½ ) of MK-5172 in the liver (t[H]½) [ Time Frame: Assessed at time of liver FNA (4, 8, 24, or 72 hours post-dose on Day 7) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • AUC[0-24 hr] for MK-5172 in the plasma over 24 hours [ Time Frame: Predose to 24 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) of MK-5172 in the plasma [ Time Frame: Predose to 24 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
  • Lowest concentration (Ctrough) of MK-5172 in the plasma [ Time Frame: Predose to 24 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
  • Time to maximum concentration (Tmax) of MK-5172 in the plasma [ Time Frame: Predose to 24 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
  • t½ of MK-5172 in the plasma [ Time Frame: Predose to 72 hours post-dose on Day 7 ] [ Designated as safety issue: No ]

Estimated Enrollment: 8
Study Start Date: October 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-5172 100 mg
Participants will receive 100 mg MK-5172 each day for 7 days and will undergo liver FNA on Day 7.
Drug: MK-5172
MK-5172, orally, 100 mg tablets, one tablet per day for 7 days.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Body Mass Index (BMI) ≥18.5 kg/m² and ≤36.0 kg/m²
  • Chronic compensated, genotype 1 HCV infection
  • No cirrhosis as confirmed by FibroSure®/Fibro Test® and/or local country procedure (e.g. transient elastography/Fibroscan)
  • No need for anticoagulants, nonsteroidal anti-inflammatory agents, and aspirin for at least fourteen (14) days preceding the initial liver biopsy and continuing throughout the entire study
  • Female participants of reproductive potential willing to use 2 medically acceptable forms of contraception for 2 weeks prior to start of treatment through 2 weeks after last study treatment
  • Male participants with partners of reproductive potential willing to use 2 medically acceptable forms of contraception from first dose to 90 days after last dose

Exclusion criteria:

  • History of stroke, chronic seizures, or major neurological disorder
  • Previous treatment with a Direct-Acting Antiviral (DAA)
  • Evidence of high grade bridging fibrosis from prior liver biopsy within 3 years of study entry
  • Evidence or history of chronic hepatitis not caused by HCV infection including but not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, or autoimmune hepatitis
  • Clinical or laboratory evidence of cirrhosis or other advanced liver disease
  • Decompensated liver disease as indicated by a history of ascites, hepatic encephalopathy, or bleeding esophageal varices
  • Diagnosed or suspected of having hepatocellular carcinoma
  • Clinically significant abnormality on an electrocardiogram (ECG)
  • Co-infection with human immunodeficiency virus (HIV)
  • Positive Hepatitis B surface antigen or other evidence of active Hepatitis B infection
  • History of gastric bypass surgery, bowel resection or other disorder that may interfere with absorption
  • History of clinically significant uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
  • Clinically significant neoplastic disease
  • Excessive use of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL], wine [118 mL], or distilled spirits [29.5 mL]) per day
  • Current regular user (including use of any illicit drugs) or history of drug (including alcohol) abuse within the last 3 months
  • Surgery, donation of 1 unit of blood (approximately 500 mL) or participation in another investigational study within a period of 4 weeks prior to the screening visit
  • History of multiple and/or severe allergies, or anaphylactic reaction or intolerability to prescription or nonprescription drugs or food
  • Pregnant or lactating
  • Expecting to donate eggs or sperm
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01537900

Contacts
Contact: Toll Free Number 1-888-577-8839

Locations
Germany
Merck Sharp & Dohme GmbH Recruiting
Haar, Germany
Contact: German Medical Information Center    49 800 673 673 673      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01537900     History of Changes
Other Study ID Numbers: 5172-010
Study First Received: February 17, 2012
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on April 17, 2014