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

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

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

Conditions
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Hepatic Insufficiency

Intervention / Treatment
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* Drug: BMS-790052


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BMS-790052 in Child-Pugh A<br> | Drug: BMS-790052<br>* Capsules, Oral, 30 mg, single dose, one day<br>|
| Active Comparator: BMS-790052 in Child-Pugh B<br> | Drug: BMS-790052<br>* Capsules, Oral, 30 mg, single dose, one day<br>|
| Active Comparator: BMS-790052 in Child-Pugh C<br> | Drug: BMS-790052<br>* Capsules, Oral, 30 mg, single dose, one day<br>|
| Active Comparator: BMS-790052 in Healthy Subjects<br> | Drug: BMS-790052<br>* Capsules, Oral, 30 mg, single dose, one day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |