Pharmacokinetic and Safety Study of Daclatasvir in Patients With Renal Impairment

Hepatitis C Clinical Trial

Official title:

Single Dose Pharmacokinetics and Safety of Daclatasvir in Subjects With Renal Function Impairment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01830205
• Other study ID #: AI444-063
• Status: Completed
• Phase: Phase 1
• First received: April 10, 2013
• Last updated: November 13, 2015
• Start date: September 2012
• Est. completion date: June 2013

Study information

• Verified date: November 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the effect of renal function impairment on the single dose pharmacokinetics of Daclatasvir.

Description:

Treatment, Parallel Assignment, Open Label, Non-Randomized, Single Dose Adaptive Design, Pharmacokinetics Study

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Meet renal function criteria in one of four categories

Exclusion Criteria:

• Unstable or uncontrolled medical conditions

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C

Intervention

Drug:
• Daclatasvir

Locations

Country	Name	City	State
United States	Davita Clinical Research	Minneapolis	Minnesota
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir	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.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir	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	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of Daclatasvir	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.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Unbound Maximum Observed Plasma Concentrations of Daclatasvir	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.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration [AUC(0-T)] of Daclatasvir	AUC(0-T) was calculated as the sum of linear trapezoids using non-compartmental analysis.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Daclatasvir	Tmax was defined as the time required to reach maximum observed plasma concentration. Tmax was directly determined from the raw plasma concentration-time data.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Plasma Half-life (T-half) of Daclatasvir	Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Apparent Total Body Clearance (CLT/F) of Daclatasvir	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.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Unbound Apparent Clearance (CLU/F) of Daclatasvir	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.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Percent Urinary Recovery (%UR) of Daclatasvir	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.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Renal Clearance (CLR) of Daclatasvir	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.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Apparent Volume of Distribution (Vd/F) of Daclatasvir	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.	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose	No
Secondary	Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events and Who Died	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.	First dose up to Day 5 post last dose for AEs; up to 30 days post last dose for SAEs	Yes
Secondary	Number of Participants With Clinically Significant Laboratory Marked Abnormalities Reported as Adverse Events	Significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator.	Baseline up to Day 5 post dose	Yes
Secondary	Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Reported as Adverse Events	The number of participants with clinically relevant changes in ECG which were considered as adverse events was determined.	Baseline up to Day 5 post dose	Yes
Secondary	Number of Participants With Out-of-range Vital Signs Reported as Adverse Events	The total number of participants with abnormal range vital signs which were considered as adverse events was determined.	Baseline up to Day 5 post dose	Yes

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