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

NCT00859053 | Completed Phase 1 Results

• 1 other identifier: AI444-013
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Hepatic Insufficiency

Outcome Measures

Primary Outcomes (8)

• 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)

• 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)

• 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/λ z, where λ 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)

• 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)

• 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)

• 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/λ z, where λ 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)

• 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/ λz, where λz 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)

• 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/λ z, where λ 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)

Secondary Outcomes (1)

• Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died

  Day 1 to end of study for AEs and, Day 1 to up to 30 days after last dose for SAE.

Study Arms (4)

BMS-790052 in Child-Pugh A

ACTIVE COMPARATOR

Drug: BMS-790052

BMS-790052 in Child-Pugh B

ACTIVE COMPARATOR

Drug: BMS-790052

BMS-790052 in Child-Pugh C

ACTIVE COMPARATOR

Drug: BMS-790052

BMS-790052 in Healthy Subjects

ACTIVE COMPARATOR

Drug: BMS-790052

Interventions

BMS-790052 DRUG

Capsules, Oral, 30 mg, single dose, one day

BMS-790052 in Child-Pugh A; BMS-790052 in Child-Pugh B; BMS-790052 in Child-Pugh C; BMS-790052 in Healthy Subjects

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (2)

Advanced Clinical Research Institute

Anaheim, California, 92801, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Hepatic Insufficiency

Interventions

daclatasvir

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2009
• First Posted: March 10, 2009
• Study Start: March 1, 2009
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: October 8, 2015
• Results First Posted: October 8, 2015

Record last verified: 2015-09

Locations

US (2)