Pharmacokinetic and Safety Study of Daclatasvir in Patients With Renal Impairment
13 novembre 2015 mis à jour par: Bristol-Myers Squibb
Single Dose Pharmacokinetics and Safety of Daclatasvir in Subjects With Renal Function Impairment
The purpose of this study is to assess the effect of renal function impairment on the single dose pharmacokinetics of Daclatasvir.
Aperçu de l'étude
Description détaillée
Treatment, Parallel Assignment, Open Label, Non-Randomized, Single Dose Adaptive Design, Pharmacokinetics Study
Type d'étude
Interventionnel
Inscription (Réel)
58
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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Florida
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Orlando, Florida, États-Unis, 32809
- Orlando Clinical Research Center
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Minnesota
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Minneapolis, Minnesota, États-Unis, 55404
- DaVita Clinical Research
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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 et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Meet renal function criteria in one of four categories
Exclusion Criteria:
- Unstable or uncontrolled medical conditions
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: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Group A (Normal renal function): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
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Autres noms:
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Expérimental: Group B (End Stage Renal Disease): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
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Autres noms:
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Expérimental: Group C (Moderate renal impairment): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
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Autres noms:
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Expérimental: Group D (Severe renal impairment): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
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Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
|
AUC(INF) was estimated by summing the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and the extrapolated area, computed by the quotient of the last observable concentration and elimination rate constant.
The pharmacokinetic (PK) analysis was based on Cockcroft-Gault (C-G) creatinine clearance (CLcr) grouping method: normal renal function, end stage renal disease (ESRD), moderate and severe renal impairment.
Mild participants were counted as per their original allocation.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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AUC(INF)u was calculated by multiplying the area under the plasma concentration-time curve from time zero extrapolated to infinite time by mean fraction of unbound drug from 1 hour post-dose time point.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Maximum Observed Plasma Concentration (Cmax) of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Maximum observed plasma concentration following drug administration from the raw plasma concentration-time data.
The plasma samples were analyzed for daclatasvir by using a validated liquid chromatography tandem mass spectrometric (LC-MS/MS) assay.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Unbound Maximum Observed Plasma Concentrations of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Unbound Maximum observed plasma concentrations (Cmaxu) was calculated by multiplying maximum observed plasma concentrations by mean fraction of unbound drug from 1 hour post-dose time point.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration [AUC(0-T)] of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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AUC(0-T) was calculated as the sum of linear trapezoids using non-compartmental analysis.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
|
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Time to Reach Maximum Observed Plasma Concentration (Tmax) of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Tmax was defined as the time required to reach maximum observed plasma concentration.
Tmax was directly determined from the raw plasma concentration-time data.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Plasma Half-life (T-half) of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Apparent Total Body Clearance (CLT/F) of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Apparent total body clearance was calculated by dividing the dose by area under the plasma concentration-time curve from time zero extrapolated to infinite time.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Unbound Apparent Clearance (CLU/F) of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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The CLU/F was calculated by dividing the apparent total body clearance by mean fraction of unbound drug from 1 hour post dose time point.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Percent Urinary Recovery (%UR) of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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The percentage of daclatasvir recovered in the urine was determined by using validated liquid chromatography-tandem mass spectrometry methods.
The sum of the percentage of dose recovered in urine from all intervals was calculated to obtain the total percentage of urinary excretion.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Renal Clearance (CLR) of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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The CLR was calculated by dividing the total amount excreted in the urine from 0 to 96 hours by the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Apparent Volume of Distribution (Vd/F) of Daclatasvir
Délai: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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The Vd/F was calculated by dividing the product of the dose and mean residence time by area under the plasma concentration-time curve from time zero extrapolated to infinite time.
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Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
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Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events and Who Died
Délai: First dose up to Day 5 post last dose for AEs; up to 30 days post last dose for SAEs
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Adverse event (AE) was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment.
SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalisation.
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First dose up to Day 5 post last dose for AEs; up to 30 days post last dose for SAEs
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Number of Participants With Clinically Significant Laboratory Marked Abnormalities Reported as Adverse Events
Délai: Baseline up to Day 5 post dose
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Significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator.
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Baseline up to Day 5 post dose
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Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Reported as Adverse Events
Délai: Baseline up to Day 5 post dose
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The number of participants with clinically relevant changes in ECG which were considered as adverse events was determined.
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Baseline up to Day 5 post dose
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Number of Participants With Out-of-range Vital Signs Reported as Adverse Events
Délai: Baseline up to Day 5 post dose
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The total number of participants with abnormal range vital signs which were considered as adverse events was determined.
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Baseline up to Day 5 post dose
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Collaborateurs et enquêteurs
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Publications et liens utiles
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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 2012
Achèvement primaire (Réel)
1 juin 2013
Achèvement de l'étude (Réel)
1 juin 2013
Dates d'inscription aux études
Première soumission
10 avril 2013
Première soumission répondant aux critères de contrôle qualité
10 avril 2013
Première publication (Estimation)
12 avril 2013
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
16 novembre 2015
Dernière mise à jour soumise répondant aux critères de contrôle qualité
13 novembre 2015
Dernière vérification
1 novembre 2015
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- AI444-063
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