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Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172) (MK-5172-013)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01390428
First received: July 7, 2011
Last updated: November 9, 2014
Last verified: November 2014
  Purpose

This study will compare the pharmacokinetics (PK) of Grazoprevir (MK-5172) when administered to participants with mild, moderate or severe hepatic insufficiency (assessed by the criteria of the Child-Pugh's scale) with the PK of Grazoprevir when administered to healthy participants.


Condition Intervention Phase
Hepatitis C
Drug: Grazoprevir
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, 3-Part, Multiple Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-5172

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Area Under the Concentration Time-curve from 0 to 24 hours (AUC0-24) of Grazoprevir [ Time Frame: Hour 0 to Hour 24 postdose on Days 1 and 10 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) of Grazoprevir [ Time Frame: Days 1 and 10 ] [ Designated as safety issue: No ]
  • Time to peak concentration (Tmax) of Grazoprevir [ Time Frame: Days 1 and 10 ] [ Designated as safety issue: No ]
  • Concentrations 24 hours post-dose (C24) of Grazoprevir [ Time Frame: 24 hours postdose on Days 1 and 10 ] [ Designated as safety issue: No ]
  • Apparent terminal half-life (t1/2) of Grazoprevir [ Time Frame: Day 10 ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: July 2011
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1-Mild Hepatic Impairment
Participants with mild hepatic impairment will receive 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.
Drug: Grazoprevir
Part 1: oral morning dose of 200 mg daily for 10 days Part 2: oral morning dose of 100 mg daily for 10 days Part 3: oral morning dose of 50 mg daily for 10 days
Experimental: Part 1-Healthy
Healthy participants will receive 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.
Drug: Grazoprevir
Part 1: oral morning dose of 200 mg daily for 10 days Part 2: oral morning dose of 100 mg daily for 10 days Part 3: oral morning dose of 50 mg daily for 10 days
Experimental: Part 2-Moderate Hepatic Impairment
Participants with moderate hepatic impairment will receive 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.
Drug: Grazoprevir
Part 1: oral morning dose of 200 mg daily for 10 days Part 2: oral morning dose of 100 mg daily for 10 days Part 3: oral morning dose of 50 mg daily for 10 days
Experimental: Part 2-Healthy
Healthy participants will receive 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.
Drug: Grazoprevir
Part 1: oral morning dose of 200 mg daily for 10 days Part 2: oral morning dose of 100 mg daily for 10 days Part 3: oral morning dose of 50 mg daily for 10 days
Experimental: Part 3-Severe Hepatic Impairment
Participants with severe hepatic impairment will receive 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Drug: Grazoprevir
Part 1: oral morning dose of 200 mg daily for 10 days Part 2: oral morning dose of 100 mg daily for 10 days Part 3: oral morning dose of 50 mg daily for 10 days
Experimental: Part 3-Healthy
Healthy participants will receive 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Drug: Grazoprevir
Part 1: oral morning dose of 200 mg daily for 10 days Part 2: oral morning dose of 100 mg daily for 10 days Part 3: oral morning dose of 50 mg daily for 10 days

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • If female, must be of non-childbearing potential or willing to use at least 2 acceptable methods of contraception from enrollment to 2 weeks after the last dose of study drug
  • No clinically significant abnormality on electrocardiogram

Hepatic Insufficiency Participants Only:

  • Other than hepatic insufficiency with features of cirrhosis, is otherwise in good health based on medical history, physical examination, vital signs, and laboratory safety tests
  • Chronic (>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology
  • Score on the Child-Pugh scale must range from 5 to 6 (mild hepatic insufficiency) to from 7 to 9 (moderate hepatic insufficiency) to from 10 to 15 (severe hepatic insufficiency)

Matched Healthy Participants Only:

- In good health based on medical history, physical examination, vital signs, and laboratory safety tests

Exclusion Criteria:

  • History of any illness that might confound the results of the study or poses an additional risk to the participant
  • History of clinically significant endocrine, gastrointestinal (other than related to their hepatic impairment), cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
  • Pregnancy
  • Estimated creatinine clearance of ≤60 mL/min
  • History of stroke, chronic seizures, or major neurological disorder
  • History of neoplastic disease (including leukemia, lymphoma, malignant melanoma), or myeloproliferative disease, regardless of the time since treatment
  • Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort, green tea, gingko, coenzyme Q, ginseng, echinacea, etc.) or nutritional supplements (e.g., garlic supplements), beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study, until the poststudy visit
  • Participated in another investigational study within 4 weeks
  • History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food

Hepatic Insufficiency Participants Only:

- Has a history of hepatitis C infection by serology, regardless of most recent viral load status.

Matched Healthy Participants Only:

  • History of any chronic and/or active hepatic disease including elevations of serum transaminases, hepatitis, biliary tract disease, or a history of any significant gastrointestinal surgery.
  • History of hepatitis C. Participants with a history of self-limited hepatitis A with complete resolution documented at least 6 months prior to entry will be eligible for inclusion
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01390428     History of Changes
Other Study ID Numbers: 5172-013
Study First Received: July 7, 2011
Last Updated: November 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatic Insufficiency
Hepatitis C
Digestive System Diseases
Flaviviridae Infections
Hepatitis
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 27, 2014