Pharmacokinetic and Safety Study of Daclatasvir in Patients With Renal Impairment
- Registration Number
- NCT01830205
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to assess the effect of renal function impairment on the single dose pharmacokinetics of Daclatasvir.
- Detailed Description
Treatment, Parallel Assignment, Open Label, Non-Randomized, Single Dose Adaptive Design, Pharmacokinetics Study
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 58
- Meet renal function criteria in one of four categories
- Unstable or uncontrolled medical conditions
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B (End Stage Renal Disease): Daclatasvir Daclatasvir Daclatasvir 60 mg tablet by mouth single dose on Day 1 Group C (Moderate renal impairment): Daclatasvir Daclatasvir Daclatasvir 60 mg tablet by mouth single dose on Day 1 Group D (Severe renal impairment): Daclatasvir Daclatasvir Daclatasvir 60 mg tablet by mouth single dose on Day 1 Group A (Normal renal function): Daclatasvir Daclatasvir Daclatasvir 60 mg tablet by mouth single dose on Day 1
- Primary Outcome Measures
Name Time Method Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir 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.
- Secondary Outcome Measures
Name Time Method Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir 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.
Percent Urinary Recovery (%UR) of Daclatasvir Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose 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.
Number of Participants With Clinically Significant Laboratory Marked Abnormalities Reported as Adverse Events Baseline up to Day 5 post dose Significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator.
Maximum Observed Plasma Concentration (Cmax) of Daclatasvir 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.
Unbound Maximum Observed Plasma Concentrations of Daclatasvir 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.
Plasma Half-life (T-half) of Daclatasvir 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.
Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration [AUC(0-T)] of Daclatasvir 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.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Daclatasvir 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.
Renal Clearance (CLR) of Daclatasvir Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose 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.
Apparent Volume of Distribution (Vd/F) of Daclatasvir Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose 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.
Apparent Total Body Clearance (CLT/F) of Daclatasvir 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.
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events and Who Died First dose up to Day 5 post last dose for AEs; up to 30 days post last dose for SAEs 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.
Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Reported as Adverse Events Baseline up to Day 5 post dose The number of participants with clinically relevant changes in ECG which were considered as adverse events was determined.
Unbound Apparent Clearance (CLU/F) of Daclatasvir 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.
Number of Participants With Out-of-range Vital Signs Reported as Adverse Events Baseline up to Day 5 post dose The total number of participants with abnormal range vital signs which were considered as adverse events was determined.
Trial Locations
- Locations (2)
Davita Clinical Research
🇺🇸Minneapolis, Minnesota, United States
Orlando Clinical Research Center
🇺🇸Orlando, Florida, United States