- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01390428
Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172-013)
16 augusti 2018 uppdaterad av: Merck Sharp & Dohme LLC
An Open-label, 3-Part, Multiple Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172)
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.
Studieöversikt
Studietyp
Interventionell
Inskrivning (Faktisk)
50
Fas
- Fas 1
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 65 år (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Ja
Kön som är behöriga för studier
Allt
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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.
|
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
|
|
Experimentell: 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.
|
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
|
|
Experimentell: 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.
|
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
|
|
Experimentell: 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.
|
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
|
|
Experimentell: 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.
|
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
|
|
Experimentell: 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.
|
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
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir
Tidsram: 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
|
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
|
|
Maximum Concentration (Cmax) of Grazoprevir
Tidsram: 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
|
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
|
|
Time to Peak Concentration (Tmax) of Grazoprevir
Tidsram: 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
|
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
|
|
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
Tidsram: Day 1 at 24 hours postdose
|
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
|
|
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Severe HI and Healthy Matched to Severe HI
Tidsram: Day 1 at 24 hours postdose
|
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
|
|
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10
Tidsram: Days 10 at 24 hours postdose
|
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
|
|
Apparent Terminal Half-life (t1/2) of Grazoprevir
Tidsram: 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
|
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
|
Samarbetspartners och utredare
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Sponsor
Publikationer och användbara länkar
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Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
28 juli 2011
Primärt slutförande (Faktisk)
5 september 2014
Avslutad studie (Faktisk)
12 september 2014
Studieregistreringsdatum
Först inskickad
7 juli 2011
Först inskickad som uppfyllde QC-kriterierna
7 juli 2011
Första postat (Uppskatta)
11 juli 2011
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
14 september 2018
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
16 augusti 2018
Senast verifierad
1 augusti 2018
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 5172-013
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
JA
IPD-planbeskrivning
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .