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Phase 1 Completed N=50 Treatment

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

OutcomeResultp-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
View full record on ClinicalTrials.gov →

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.

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