Phase 1
Completed N=50
Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172-013)
Source: ClinicalTrials.gov NCT01390428 ↗Enrolled (actual)
50
Serious AEs
2.0%
Results posted
Mar 2016
Primary outcomePrimary: Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir — 1.71; 1.42; 1.61; 0.321 uM*hr
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir |
1.71; 1.42; 1.61; 0.321; 1.17; 0.0592 | — |
| PRIMARY Maximum Concentration (Cmax) of Grazoprevir |
0.257; 0.305; 0.433; 0.0580; 0.238; 0.0157 | — |
| PRIMARY Time to Peak Concentration (Tmax) of Grazoprevir |
3.50; 2.50; 2.00; 1.75; 1.75; 1.50 | — |
| 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 |
21.4; 11.5; 17.7; 5.90 | — |
| PRIMARY Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Severe HI and Healthy Matched to Severe HI |
15.6; 1.86 | — |
| PRIMARY Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10 |
32.6; 17.0; 48.9; 13.6; 55.0; 5.89 | — |
| PRIMARY Apparent Terminal Half-life (t1/2) of Grazoprevir |
54.24; 35.85; 39.59; 39.80; 42.00; 31.02 | — |
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
Data sourced from ClinicalTrials.gov (NCT01390428). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.