- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01390428
Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172-013)
An Open-label, 3-Part, Multiple Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172)
Aperçu de l'étude
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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
|
|
Expérimental: 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
|
|
Expérimental: 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
|
|
Expérimental: 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
|
|
Expérimental: 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
|
|
Expérimental: 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
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
|
Collaborateurs et enquêteurs
Parrainer
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système digestif
- Infections par virus à ARN
- Maladies virales
- Infections
- Infections transmissibles par le sang
- Maladies transmissibles
- Maladies du foie
- Infections à Flaviviridae
- Hépatite, virale, humaine
- Hépatite
- Insuffisance hépatique
- Insuffisance hépatique
- Hépatite C
- Agents anti-infectieux
- Agents antiviraux
- Grazoprévir
Autres numéros d'identification d'étude
- 5172-013
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
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