Single-Dose Pharmacokinetics of BMS-790052 in Participants With Hepatic Impairment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00859053
First received: March 6, 2009
Last updated: September 9, 2015
Last verified: September 2015
  Purpose
The purpose of this study is to assess the effects of hepatic impairment on the single dose pharmacokinetics of BMS-790052.

Condition Intervention Phase
Hepatic Insufficiency
Drug: BMS-790052
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Single-Dose Pharmacokinetics of BMS-790052 in Subjects With Hepatic Impairment Compared to Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) of BMS-790052 [ Time Frame: Pre-dose (0), 0.5,1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants) ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration following drug administration from the raw plasma concentration-time data. The plasma samples were analysed for BMS-790052 by using a validated liquid chromatography tandem mass spectrometric (LC-MS/MS) assay.

  • Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-T)] of BMS-790052 [ Time Frame: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants) ] [ Designated as safety issue: No ]
    AUC(0-T) was calculated by the sum of linear trapezoids using non-compartmental analysis.

  • Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of BMS-790052 [ Time Frame: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants) ] [ Designated as safety issue: No ]
    AUC(INF) was estimated as AUC(0-T) + Ct/λ z, where λ z was the terminal elimination rate constant and Ct was the last observable concentration.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of BMS-790052 [ Time Frame: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants) ] [ Designated as safety issue: No ]
    Tmax was defined as the time required to reach maximum observed plasma concentration. Tmax was directly determined from the raw plasma concentration-time data.

  • Terminal Half-life (T-HALF) of BMS-790052 [ Time Frame: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants) ] [ Designated as safety issue: No ]
    Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body.

  • Apparent Total Body Clearance (CLT/F) of BMS-790052 [ Time Frame: Pre-dose (0), 0.5,1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants) ] [ Designated as safety issue: No ]
    Apparent total body clearance was calculated as dose/AUC(INF). AUC(INF) was estimated as AUC(0-T) + Ct/λ z, where λ z was the terminal elimination rate constant and Ct was the last observable concentration.

  • Apparent Clearance of Free BMS-790052 (CLu/F) [ Time Frame: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants) ] [ Designated as safety issue: No ]
    CLu/F was calculated by dividing the apparent total body clearance (CLT/F) by mean fraction of unbound drug (fu) for both (1 hour and 4 hour post dose) time points combined. Apparent total body clearance was calculated as dose/AUC(INF). AUC(INF) was estimated as AUC(0-T) + Ct/ λz, where λz was the terminal elimination rate constant and Ct was the last observable concentration.

  • The Apparent Volume of Distribution at Steady State (Vss/F) [ Time Frame: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants) ] [ Designated as safety issue: No ]
    Apparent volume of distribution was calculated by dividing the product of the dose and mean residence time (MRT) by AUC(INF). AUC(INF) was estimated as AUC(0-T) + Ct/λ z, where λ z was the terminal elimination rate constant and Ct was the last observable concentration.


Secondary Outcome Measures:
  • Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died [ Time Frame: Day 1 to end of study for AEs and, Day 1 to up to 30 days after last dose for SAE. ] [ Designated as safety issue: Yes ]
    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 hospitalization. Study Discharge (end of study) was Day 4 (healthy participants) or Day 5 (hepatically impaired participants).


Enrollment: 46
Study Start Date: March 2009
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: BMS-790052 in Child-Pugh A Drug: BMS-790052
Capsules, Oral, 30 mg, single dose, one day
Active Comparator: BMS-790052 in Child-Pugh B Drug: BMS-790052
Capsules, Oral, 30 mg, single dose, one day
Active Comparator: BMS-790052 in Child-Pugh C Drug: BMS-790052
Capsules, Oral, 30 mg, single dose, one day
Active Comparator: BMS-790052 in Healthy Subjects Drug: BMS-790052
Capsules, Oral, 30 mg, single dose, one day

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Key Inclusion Criteria:

  • Male and female subjects aged 18 to 70 years, with hepatic impairment conforming to Child-Pugh class A, B or C
  • Healthy subjects to the extent possible matched to the first four hepatically impaired subject in each Child-Pugh class with regard to age (approximately ± 10 years), body weight (approximately ± 20%) and gender

Key Exclusion Criteria:

  • History of esophageal and gastric variceal bleeding within past 6 months
  • Primarily cholestatic liver diseases
  • Active alcoholic hepatitis
  • Stable encephalopathy of >= Stage 2
  • Presence of severe ascites or edema
  • Presence of hepatopulmonary or hepatorenal syndrome
  • Positive for HCV, unless HCV RNA is undetectable
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00859053

Locations
United States, California
Advanced Clinical Research Institute
Anaheim, California, United States, 92801
United States, Florida
Orlando Clinical Research Center
Orlando, Florida, United States, 32809
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00859053     History of Changes
Other Study ID Numbers: AI444-013 
Study First Received: March 6, 2009
Results First Received: August 10, 2015
Last Updated: September 9, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on July 21, 2016