A Study to Evaluate the Effects of Multiple Doses of FG-4592 on the Exposure, Safety and Tolerability and Effect of Warfarin in Healthy Subjects
26 septembre 2014 mis à jour par: Astellas Pharma Europe B.V.
A Phase 1, Open-label, One-sequence Crossover Study to Evaluate the Effect of Multiple Doses of FG 4592 on the Pharmacokinetics of Warfarin in Healthy Subjects
This study will determine the effect of multiple doses of FG-4592 on the pharmacokinetics (PK) of a single dose of warfarin.
It will evaluate the safety and tolerability of warfarin alone and in combination with multiple doses of FG-4592, and will evaluate the effect of multiple doses of FG-4592 on the pharmacodynamics (PD) of warfarin.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
The study consists of 2 periods, separated by a washout period (a minimum of 14 days after warfarin dosing on Day 1, Period 1). Screening takes place from Day -22 to Day -2.
Subjects are admitted to the clinical unit on Day -1 of Period 1. On Day 1 of the first period, subjects receive a single oral dose of warfarin. After completion of all assessments on Day 8, subjects are discharged from the clinical unit on the condition that there are no medical reasons for a prolonged stay. They return to the clinical unit on Day -1 of the second period, after the washout period.
In Period 2, the subjects receive multiple doses of FG 4592. On Day 7 of Period 2, FG 4592 is given concomitantly with warfarin. After completion of all assessments on Day 16 of Period 2, subjects are discharged from the clinic on the condition that there are no medical reasons for a prolonged stay. The subjects return for an End of Study Visit (ESV) 5 to 9 days after the last assessment of Period 2 (or after early withdrawal).
Safety assessments are performed throughout the study. Blood and urine samples are collected for PK and PD assessments.
Type d'étude
Interventionnel
Inscription (Réel)
22
Phase
- La phase 1
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Berlin, Allemagne, 14050
- Parexel International GmbH
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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 55 ans (Adulte)
Accepte les volontaires sains
Oui
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control.
- Male subject must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
- Female subject must be either of non-childbearing potential or, if of childbearing potential, must have a negative pregnancy test at screening and Day -1 and must use two forms of birth control.
- Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration.
Exclusion Criteria:
- Subject has a known or suspected hypersensitivity to FG 4592, warfarin, or any components of the formulations used.
- Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to admission to the clinical unit [Day -1].
- Subject is lactose intolerant.
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: Science basique
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: warfarin and FG-4592
Single dose of warfarin and Multiple doses of FG-4592 in combination with a single dose of warfarin
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Oral
Autres noms:
Oral
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
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PK of S-warfarin and R-warfarin in plasma measured by area under the curve from the time of dosing extrapolated to time infinity (AUCinf)
Délai: Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
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Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
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PK of S-warfarin and R-warfarin in plasma measured by maximum concentration (Cmax)
Délai: Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
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Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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PK profile of S-warfarin and R-warfarin in plasma
Délai: Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
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area under the concentration-time curve from the time of dosing to the last measurable concentration (Clast) (AUClast), unbound AUC from the time of dosing to Clast (AUClast,u), AUC from the time of dosing extrapolated to time infinity (AUCinf), unbound AUC extrapolated to infinity (AUCinf,u), maximum unbound plasma concentration (Cmax,u), apparent total body clearance after extra-vascular dosing (CL/F), unbound apparent total body clearance after extravascular dosing (CLu/F), fraction unbound (fu), time interval between the time of dosing and the first measurable concentration (tlag), time of the maximum concentration (tmax), terminal elimination half-life (t1/2), apparent volume of distribution during the terminal elimination phase after single extravascular dosing (Vz/F), unbound apparent volume of distribution during terminal phase after oral administration (Vz,u/F)
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Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
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PK profile of FG-4592 in plasma
Délai: Period 2 (Day 1 to Day 15)
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AUC from time point 0 to time point 24 hours (AUC0-24h), AUClast, AUCinf , Cmax, concentration at pre-dose for repeated dosing (Ctrough), tmax, t1/2, CL/F, and Vz/F
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Period 2 (Day 1 to Day 15)
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PK profile of FG-4592 in urine
Délai: Period 2 (Day 7 to Day 8)
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renal clearance (CLR), unbound CLR from time point 0 to 24 hours (CLR,0-24h), cumulative amount of drug excreted unchanged into urine from time of dosing extrapolated to time infinity (Aeinf), percent of drug excreted unchanged into urine from time of dosing extrapolated to time infinity in percent of dose (Aeinf%), cumulative amount of drug excreted unchanged into urine, from time of dosing up to the collection time of the last measurable concentration (Aelast), percent of drug excreted into urine from time of dosing up to the collection time of the last measurable concentration in percent of dose (Aelast%), cumulative amount of drug excreted unchanged into urine, from time of dosing up to the collection time of 24 hours (Ae0 24h), cumulative amount of drug excreted unchanged into urine, from time of dosing up to the collection time of 24 hours in percent of dose (Ae0-24h%)
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Period 2 (Day 7 to Day 8)
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Pharmacodynamics profile of warfarin in plasma
Délai: Period 1 Day 1 to to ESV (5 to 9 days after the last protocol defined assessment of Period 2 (or after early withdrawal))
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area under the Prothrombin Time (PT)-time curve from the time of dosing until the last sample collected (AUCPT,last), maximal PT (PTmax), time to reach PTmax (tPT,max), area under the International Normalized Ratio (INR)-time curve from the time of dosing until the last sample collected (AUCINR,last), maximal INR after Drug Administration (INRmax), time to reach the INRmax (tINR,max)
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Period 1 Day 1 to to ESV (5 to 9 days after the last protocol defined assessment of Period 2 (or after early withdrawal))
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Safety profile
Délai: Screening (Day -22 to Day -2) to ESV (5 to 9 days after the last protocol defined assessment of Period 2 (or after early withdrawal))
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Safety profile includes Adverse Events (AEs), vital signs, physical examination, laboratory tests, electrocardiogram (ECG)
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Screening (Day -22 to Day -2) to ESV (5 to 9 days after the last protocol defined assessment of Period 2 (or after early withdrawal))
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Directeur d'études: Study Physician, Astellas Pharma Europe B.V.
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
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 septembre 2013
Achèvement primaire (Réel)
1 novembre 2013
Achèvement de l'étude (Réel)
1 novembre 2013
Dates d'inscription aux études
Première soumission
10 juin 2014
Première soumission répondant aux critères de contrôle qualité
26 septembre 2014
Première publication (Estimation)
30 septembre 2014
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
30 septembre 2014
Dernière mise à jour soumise répondant aux critères de contrôle qualité
26 septembre 2014
Dernière vérification
1 septembre 2014
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 1517-CL-0509
- 2013-001043-31 (Numéro EudraCT)
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