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

NCT ID: NCT01390428

Last Updated: 2018-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-28
• Study Completion Date: 2014-09-12

Brief Summary

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.

Conditions

Hepatitis C

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1-Mild Hepatic Impairment (HI)

Participants with mild hepatic impairment will receive 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

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

Part 1-Healthy Matched to Mild HI

Healthy participants will receive 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

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

Part 2-Moderate HI

Participants with moderate hepatic impairment will receive 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

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

Part 2-Healthy Matched to Moderate HI

Healthy participants will receive 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

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

Part 3-Severe HI

Participants with severe hepatic impairment will receive 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

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

Part 3-Healthy Matched to Severe HI

Healthy participants will receive 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Caro L, Wenning L, Guo Z, Fraser IP, Fandozzi C, Talaty J, Panebianco D, Ho M, Uemura N, Reitmann C, Angus P, Gane E, Marbury T, Smith WB, Iwamoto M, Butterton JR, Yeh WW. Effect of Hepatic Impairment on the Pharmacokinetics of Grazoprevir, a Hepatitis C Virus Protease Inhibitor. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e00813-17. doi: 10.1128/AAC.00813-17. Print 2017 Dec.

Reference Type: RESULT

PMID: 28947470 (View on PubMed)

Other Identifiers

5172-013

Identifier Type: -

Identifier Source: org_study_id