Pharmacokinetic and Safety Study of Daclatasvir in Patients With Renal Impairment
13 november 2015 uppdaterad av: 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.
Studieöversikt
Detaljerad beskrivning
Treatment, Parallel Assignment, Open Label, Non-Randomized, Single Dose Adaptive Design, Pharmacokinetics Study
Studietyp
Interventionell
Inskrivning (Faktisk)
58
Fas
- Fas 1
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Florida
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Orlando, Florida, Förenta staterna, 32809
- Orlando Clinical Research Center
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Minnesota
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Minneapolis, Minnesota, Förenta staterna, 55404
- DaVita Clinical Research
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-
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 och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria:
- Meet renal function criteria in one of four categories
Exclusion Criteria:
- Unstable or uncontrolled medical conditions
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 |
|---|---|
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Experimentell: Group A (Normal renal function): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
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Andra namn:
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Experimentell: Group B (End Stage Renal Disease): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
|
Andra namn:
|
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Experimentell: Group C (Moderate renal impairment): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
|
Andra namn:
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Experimentell: Group D (Severe renal impairment): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
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Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir
Tidsram: 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)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.
|
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
Tidsram: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
|
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
Tidsram: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
|
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
Tidsram: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
|
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
Tidsram: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
|
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
Tidsram: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
|
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
Tidsram: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
|
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
Tidsram: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
|
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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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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Studieavstämningsdatum
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Studera stora datum
Studiestart
1 september 2012
Primärt slutförande (Faktisk)
1 juni 2013
Avslutad studie (Faktisk)
1 juni 2013
Studieregistreringsdatum
Först inskickad
10 april 2013
Först inskickad som uppfyllde QC-kriterierna
10 april 2013
Första postat (Uppskatta)
12 april 2013
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
16 november 2015
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
13 november 2015
Senast verifierad
1 november 2015
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- AI444-063
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