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

Hepatic Insufficiency Clinical Trial

Official title:

Single-Dose Pharmacokinetics of BMS-790052 in Subjects With Hepatic Impairment Compared to Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00859053
• Other study ID #: AI444-013
• Status: Completed
• Phase: Phase 1
• First received: March 6, 2009
• Last updated: September 9, 2015
• Start date: March 2009
• Est. completion date: September 2009

Study information

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

Clinical Trial Summary

The purpose of this study is to assess the effects of hepatic impairment on the single dose pharmacokinetics of BMS-790052.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Hepatic Insufficiency

Intervention

Drug:
• BMS-790052
Capsules, Oral, 30 mg, single dose, one day

Locations

Country	Name	City	State
United States	Advanced Clinical Research Institute	Anaheim	California
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	Maximum Observed Plasma Concentration (Cmax) of BMS-790052	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.	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)	No
Primary	Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-T)] of BMS-790052	AUC(0-T) was calculated by the sum of linear trapezoids using non-compartmental analysis.	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)	No
Primary	Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of BMS-790052	AUC(INF) was estimated as AUC(0-T) + Ct/? z, where ? z was the terminal elimination rate constant and Ct was the last observable concentration.	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)	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of BMS-790052	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, 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)	No
Primary	Terminal Half-life (T-HALF) of BMS-790052	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, 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)	No
Primary	Apparent Total Body Clearance (CLT/F) of BMS-790052	Apparent total body clearance was calculated as dose/AUC(INF). AUC(INF) was estimated as AUC(0-T) + Ct/? z, where ? z was the terminal elimination rate constant and Ct was the last observable concentration.	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)	No
Primary	Apparent Clearance of Free BMS-790052 (CLu/F)	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/ ?z, where ?z was the terminal elimination rate constant and Ct was the last observable concentration.	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)	No
Primary	The Apparent Volume of Distribution at Steady State (Vss/F)	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/? z, where ? z was the terminal elimination rate constant and Ct was the last observable concentration.	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)	No
Secondary	Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died	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).	Day 1 to end of study for AEs and, Day 1 to up to 30 days after last dose for SAE.	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form