ClinicalTrials.gov
ClinicalTrials.gov Menu

Pharmacokinetic and Safety Study of Daclatasvir in Patients With Renal Impairment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01830205
Recruitment Status : Completed
First Posted : April 12, 2013
Results First Posted : November 16, 2015
Last Update Posted : November 16, 2015
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: Daclatasvir Phase 1

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single Dose Pharmacokinetics and Safety of Daclatasvir in Subjects With Renal Function Impairment
Study Start Date : September 2012
Actual Primary Completion Date : June 2013
Actual Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests
Drug Information available for: Daclatasvir

Arm Intervention/treatment
Experimental: Group A (Normal renal function): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
Drug: Daclatasvir
Other Name: BMS-790052

Experimental: Group B (End Stage Renal Disease): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
Drug: Daclatasvir
Other Name: BMS-790052

Experimental: Group C (Moderate renal impairment): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
Drug: Daclatasvir
Other Name: BMS-790052

Experimental: Group D (Severe renal impairment): Daclatasvir
Daclatasvir 60 mg tablet by mouth single dose on Day 1
Drug: Daclatasvir
Other Name: BMS-790052




Primary Outcome Measures :
  1. Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir [ Time Frame: 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 :
  1. Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir [ Time Frame: 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.

  2. Maximum Observed Plasma Concentration (Cmax) of Daclatasvir [ Time Frame: 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.

  3. Unbound Maximum Observed Plasma Concentrations of Daclatasvir [ Time Frame: 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.

  4. Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration [AUC(0-T)] of Daclatasvir [ Time Frame: 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.

  5. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Daclatasvir [ Time Frame: 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.

  6. Plasma Half-life (T-half) of Daclatasvir [ Time Frame: 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.

  7. Apparent Total Body Clearance (CLT/F) of Daclatasvir [ Time Frame: 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.

  8. Unbound Apparent Clearance (CLU/F) of Daclatasvir [ Time Frame: 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.

  9. Percent Urinary Recovery (%UR) of Daclatasvir [ Time Frame: 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.

  10. Renal Clearance (CLR) of Daclatasvir [ Time Frame: 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.

  11. Apparent Volume of Distribution (Vd/F) of Daclatasvir [ Time Frame: 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.

  12. Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events and Who Died [ Time Frame: 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.

  13. Number of Participants With Clinically Significant Laboratory Marked Abnormalities Reported as Adverse Events [ Time Frame: 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.

  14. Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Reported as Adverse Events [ Time Frame: 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.

  15. Number of Participants With Out-of-range Vital Signs Reported as Adverse Events [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Meet renal function criteria in one of four categories

Exclusion Criteria:

- Unstable or uncontrolled medical conditions


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01830205


Locations
United States, Florida
Orlando Clinical Research Center
Orlando, Florida, United States, 32809
United States, Minnesota
Davita Clinical Research
Minneapolis, Minnesota, United States, 55404
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01830205     History of Changes
Other Study ID Numbers: AI444-063
First Posted: April 12, 2013    Key Record Dates
Results First Posted: November 16, 2015
Last Update Posted: November 16, 2015
Last Verified: November 2015

Additional relevant MeSH terms:
Hepatitis C
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases