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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hepatitis C

Treatments: Drug: Grazoprevir

Study type: Interventional

Funder types: Industry

Identifiers

NCT01390428

5172-013

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

50 participants in 6 patient groups

Part 1-Mild Hepatic Impairment (HI)

Experimental group

Description:

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

Treatment:

Drug: Grazoprevir

Part 1-Healthy Matched to Mild HI

Experimental group

Description:

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

Treatment:

Drug: Grazoprevir

Part 2-Moderate HI

Experimental group

Description:

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

Treatment:

Drug: Grazoprevir

Part 2-Healthy Matched to Moderate HI

Experimental group

Description:

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

Treatment:

Drug: Grazoprevir

Part 3-Severe HI

Experimental group

Description:

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

Treatment:

Drug: Grazoprevir

Part 3-Healthy Matched to Severe HI

Experimental group

Description:

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

Treatment:

Drug: Grazoprevir