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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 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: August 14, 2014
Last verified: August 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: October 2014
Estimated Primary Completion Date: October 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: August 14, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 21, 2014