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

Hepatitis C Clinical Trial

Official title:

An Open-label, 3-Part, Multiple Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01390428
• Other study ID #: 5172-013
• Status: Completed
• Phase: Phase 1
• Start date: July 28, 2011
• Est. completion date: September 12, 2014

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 12, 2014
• Est. primary completion date: September 5, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatic Insufficiency
• Hepatitis C

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir	Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma AUC0-24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.	Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Primary	Maximum Concentration (Cmax) of Grazoprevir	Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Cmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.	Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Primary	Time to Peak Concentration (Tmax) of Grazoprevir	Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Tmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.	Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Primary	Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI	Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.	Day 1 at 24 hours postdose
Primary	Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Severe HI and Healthy Matched to Severe HI	Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.	Day 1 at 24 hours postdose
Primary	Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10	Blood samples were collected at 24 hours post-dose on Day 10 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.	Days 10 at 24 hours postdose
Primary	Apparent Terminal Half-life (t1/2) of Grazoprevir	Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Day 10 in order to determine the plasma t1/2 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.	Day 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose