Trial Outcomes & Findings for Single-Dose Pharmacokinetics of BMS-790052 in Participants With Hepatic Impairment (NCT NCT00859053)
NCT ID: NCT00859053
Last Updated: 2015-10-08
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
46 participants
Primary outcome timeframe
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)
Results posted on
2015-10-08
Participant Flow
A total of 46 participants were enrolled in the study, of which 30 participants were treated with study drug and 16 participants were not treated with study drug as they no longer met study criteria.
Participant milestones
| Measure |
Child Pugh Class-A
Participants with mild liver damage were administered with single oral dose of 30 milligrams (mg) (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
12
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Single-Dose Pharmacokinetics of BMS-790052 in Participants With Hepatic Impairment
Baseline characteristics by cohort
| Measure |
Child Pugh Class-A
n=6 Participants
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 Participants
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 Participants
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
< 65 years
|
6 participants
n=99 Participants
|
5 participants
n=107 Participants
|
5 participants
n=206 Participants
|
12 participants
n=7 Participants
|
28 participants
n=31 Participants
|
|
Age, Customized
>= 65 years
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
0 participants
n=7 Participants
|
2 participants
n=31 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
18 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: 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)Population: Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles).
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.
Outcome measures
| Measure |
Child Pugh Class-A
n=6 Participants
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 Participants
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 Participants
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of BMS-790052
|
380 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 44
|
382 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
317 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 65
|
698 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 30
|
PRIMARY outcome
Timeframe: 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)Population: Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles).
AUC(0-T) was calculated by the sum of linear trapezoids using non-compartmental analysis.
Outcome measures
| Measure |
Child Pugh Class-A
n=6 Participants
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 Participants
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 Participants
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-T)] of BMS-790052
|
4151 ng*hour (h)/mL
Geometric Coefficient of Variation 43
|
4490 ng*hour (h)/mL
Geometric Coefficient of Variation 38
|
4534 ng*hour (h)/mL
Geometric Coefficient of Variation 74
|
7165 ng*hour (h)/mL
Geometric Coefficient of Variation 24
|
PRIMARY outcome
Timeframe: 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)Population: Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles).
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.
Outcome measures
| Measure |
Child Pugh Class-A
n=6 Participants
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 Participants
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 Participants
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of BMS-790052
|
4174 ng* h/mL
Geometric Coefficient of Variation 43
|
4550 ng* h/mL
Geometric Coefficient of Variation 39
|
4649 ng* h/mL
Geometric Coefficient of Variation 78
|
7286 ng* h/mL
Geometric Coefficient of Variation 25
|
PRIMARY outcome
Timeframe: 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)Population: Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles).
Tmax was defined as the time required to reach maximum observed plasma concentration. Tmax was directly determined from the raw plasma concentration-time data.
Outcome measures
| Measure |
Child Pugh Class-A
n=6 Participants
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 Participants
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 Participants
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of BMS-790052
|
1.5 hours
Interval 1.0 to 2.0
|
1.0 hours
Interval 1.0 to 4.0
|
1.5 hours
Interval 1.0 to 4.0
|
1.3 hours
Interval 1.0 to 2.0
|
PRIMARY outcome
Timeframe: 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)Population: Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles).
Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body.
Outcome measures
| Measure |
Child Pugh Class-A
n=6 Participants
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 Participants
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 Participants
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
Terminal Half-life (T-HALF) of BMS-790052
|
12.3 hours
Standard Deviation 2.49
|
15.0 hours
Standard Deviation 4.59
|
17.2 hours
Standard Deviation 10.55
|
12.4 hours
Standard Deviation 2.23
|
PRIMARY outcome
Timeframe: 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)Population: Analysis was performed in PK set population.
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.
Outcome measures
| Measure |
Child Pugh Class-A
n=6 Participants
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 Participants
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 Participants
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
Apparent Total Body Clearance (CLT/F) of BMS-790052
|
120 milliliter/minute (mL/min)
Geometric Coefficient of Variation 85
|
110 milliliter/minute (mL/min)
Geometric Coefficient of Variation 47
|
108 milliliter/minute (mL/min)
Geometric Coefficient of Variation 78
|
69 milliliter/minute (mL/min)
Geometric Coefficient of Variation 29
|
PRIMARY outcome
Timeframe: 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)Population: Analysis was performed in PK population.
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.
Outcome measures
| Measure |
Child Pugh Class-A
n=6 Participants
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 Participants
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 Participants
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
Apparent Clearance of Free BMS-790052 (CLu/F)
|
19529 mL/min
Geometric Coefficient of Variation 66
|
12028 mL/min
Geometric Coefficient of Variation 52
|
12468 mL/min
Geometric Coefficient of Variation 61
|
11796 mL/min
Geometric Coefficient of Variation 33
|
PRIMARY outcome
Timeframe: 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)Population: Analysis was performed in PK population.
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.
Outcome measures
| Measure |
Child Pugh Class-A
n=6 Participants
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 Participants
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 Participants
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
The Apparent Volume of Distribution at Steady State (Vss/F)
|
98557 mL
Geometric Coefficient of Variation 67
|
111612 mL
Geometric Coefficient of Variation 24
|
123034 mL
Geometric Coefficient of Variation 56
|
61250 mL
Geometric Coefficient of Variation 19
|
SECONDARY outcome
Timeframe: Day 1 to end of study for AEs and, Day 1 to up to 30 days after last dose for SAE.Population: Analysis was done in safety population, defined as all the participants who received study medication.
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).
Outcome measures
| Measure |
Child Pugh Class-A
n=6 Participants
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 Participants
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 Participants
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 Participants
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died
Discontinuations due to AEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Child Pugh Class-A
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Child Pugh Class-B
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Child Pugh Class-C
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Healthy Participants
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Child Pugh Class-A
n=6 participants at risk
Participants with mild liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-B
n=6 participants at risk
Participants with moderate liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Child Pugh Class-C
n=6 participants at risk
Participants with severe liver damage were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
Healthy Participants
n=12 participants at risk
Healthy participants were administered with single oral dose of 30 mg (3 x 10 mg capsules) of BMS-790052 after 10 hours overnight fasting.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/12
|
|
General disorders
Malaise
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/12
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
8.3%
1/12
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/12
|
|
Nervous system disorders
Headache
|
16.7%
1/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/12
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/12
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/12
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Limb discomfort
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/12
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER