Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Participants With Hepatitis C (MK-2248-002)
5 juin 2015 mis à jour par: Merck Sharp & Dohme LLC
A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Subjects With Hepatitis C Infection
The objective of this study is to identify a safe dose of MK-2248 in participants with Hepatitis C Virus (HCV) that mediates at least a 3 log10 reduction in viral load (VL) from baseline.
It is anticipated that once-daily administration of a safe and well tolerated dose of MK-2248 will reduce VL by at least 3 log10 IU/mL.
Aperçu de l'étude
Description détaillée
In this Phase 1b study, the pharmacokinetic (PK), pharmacodynamic (PD), and safety profile of MK-2248 in HCV-infected participants will be evaluated as follows: Part I will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (A, B, C, and D).
Part II will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (E, F, G, and H).
Part III will assess sequentially ascending MK-2248 doses ranging up to ≤800 mg in 2 panels (I and J).
The potential relationship between plasma MK-2248 levels and VL reduction will be determined.
Type d'étude
Interventionnel
Inscription (Réel)
13
Phase
- La phase 1
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 65 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- clinical diagnosis of chronic HCV defined by positive serology for HCV or positive HCV RNA for at least 6 months and detectable HCV RNA in peripheral blood ≥10^5 IU/mL at screening
- Body Mass Index (BMI) ≥18 to <37 kg/m^2
- in good health other than HCV infection with normal laboratory values
Exclusion Criteria:
- history of clinically significant and not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic (excepting HCV infection), immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
- history of cancer other than adequately treated non-melanomatous skin carcinoma, malignancies which have been successfully treated ≥10 years prior with no recurrence, or cancer that is unlikely to sustain a recurrence for the duration of the trial
- 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
- positive for hepatitis B surface antigen or human immunodeficiency virus
- had major surgery or lost 1 unit of blood within 4 weeks prior to screening
- QTc interval ≥470 msec (males) or ≥480 msec (females)
- received prior treatment with other HCV inhibitors
- clinical or laboratory evidence of decompensated liver disease
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Part I: MK-2248 200 mg (Panel A)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Expérimental: Part I: MK-2248 ≤800 mg (Panel B)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Expérimental: Part I: MK-2248 ≤800 mg (Panel C)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Expérimental: Part I: MK-2248 ≤800 mg (Panel D)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Expérimental: Part II: MK-2248 200 mg (Panel E)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Expérimental: Part II: MK-2248 ≤800 mg (Panel F)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Expérimental: Part II: MK-2248 ≤800 mg (Panel G)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Expérimental: Part II: MK-2248 ≤800 mg (Panel H)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Expérimental: Part III: MK-2248 ≤800 mg (Panel I)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Expérimental: Part III: MK-2248 ≤800 mg (Panel J)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
|
Maximum change from baseline in VL
Délai: Up to Day 42
|
Up to Day 42
|
|
Number of participants experiencing an adverse event (AE)
Délai: Up to Day 42
|
Up to Day 42
|
|
Number of participants who discontinue from study treatment due to an AE
Délai: Up to Day 7
|
Up to Day 7
|
Mesures de résultats secondaires
Mesure des résultats |
Délai |
|---|---|
|
Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s)
Délai: Up to Day 10
|
Up to Day 10
|
|
Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s)
Délai: Up to Day 10
|
Up to Day 10
|
|
Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)
Délai: Up to Day 10
|
Up to Day 10
|
|
Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs
Délai: Up to Day 10
|
Up to Day 10
|
|
Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma
Délai: Up to Day 10
|
Up to Day 10
|
|
Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma
Délai: Up to Day 10
|
Up to Day 10
|
|
Total clearance (amount of drug cleared relative to the total systemically available amount per unit time [CL/F]) of MK-2248 in plasma
Délai: Up to Day 10
|
Up to Day 10
|
|
Apparent volume of distribution (V/F) of MK-2248 in plasma
Délai: Up to Day 10
|
Up to Day 10
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 juillet 2014
Achèvement primaire (Réel)
1 novembre 2014
Achèvement de l'étude (Réel)
1 avril 2015
Dates d'inscription aux études
Première soumission
10 juin 2014
Première soumission répondant aux critères de contrôle qualité
10 juin 2014
Première publication (Estimation)
11 juin 2014
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
8 juin 2015
Dernière mise à jour soumise répondant aux critères de contrôle qualité
5 juin 2015
Dernière vérification
1 juin 2015
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 2248-002
- 2014-001494-14 (Numéro EudraCT)
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