Hepatic InsufficiencyPhase 1NCT00859053

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

A Phase 1 study testing BMS-790052 in people with Hepatic Insufficiency, run by Bristol-Myers Squibb at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Hepatic Insufficiency
What is being tested?: BMS-790052
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 46 participants
Where: 2 sitesUnited States
Study dates: Mar 2009to Sep 2009
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Advanced Clinical Research Institute
Anaheim, California, 92801
Orlando Clinical Research Center
Orlando, Florida, 32809

Other trials in United States

About this study

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

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

Conditions: Hepatic Insufficiency
Being tested: BMS-790052
Medical subject headings: Hepatic Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT00859053
Study group	Role	What they receive
BMS-790052 in Child-Pugh A	Active comparator	Not described Receives: Drug: BMS-790052
BMS-790052 in Child-Pugh B	Active comparator	Not described Receives: Drug: BMS-790052
BMS-790052 in Child-Pugh C	Active comparator	Not described Receives: Drug: BMS-790052
BMS-790052 in Healthy Subjects	Active comparator	Not described Receives: Drug: BMS-790052

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2009Sep 2009

First posted10 Mar 2009 (estimated)
Study startMar 2009
Primary completionSep 2009
Study completionSep 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hepatic InsufficiencyStudies of the same condition, open and under way.
More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00859053
Sponsor's protocol ID: AI444-013
Status last verified: Sep 2015
First submitted: 6 Mar 2009
Last updated: 8 Oct 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Active, not recruiting
LiverPAL: A Trial of Inpatient Palliative Care for Patients With Advanced Liver Disease
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RecruitingObservational study
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All Hepatic Insufficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Single-Dose Pharmacokinetics of BMS-790052 in Subjects With Hepatic Impairment Compared to Healthy Subjects
ClinicalTrials.gov ID: NCT00859053
Acronym / sponsor ID: AI444-013
Conditions: Hepatic Insufficiency
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Study start: Mar 2009
Primary completion: Sep 2009 (actual)
Study completion: Sep 2009 (actual)
First posted: 10 Mar 2009 (estimated)
Results: Posted 8 Oct 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
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

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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 (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BMS-790052Capsules, Oral, 30 mg, single dose, one day	Drug	BMS-790052 in Child-Pugh A, BMS-790052 in Child-Pugh B, BMS-790052 in Child-Pugh C, BMS-790052 in Healthy Subjects

Primary outcome

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)
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)
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)
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)
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)
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)
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)
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)
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.

1 secondary outcome

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.

Results and safety

Results posted to the registry on 8 Oct 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Child Pugh Class-A	6	6
Child Pugh Class-B	6	6
Child Pugh Class-C	6	6
Healthy Participants	12	12

Primary outcome: 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). Geometric mean (Geometric Coefficient of Variation). Unit: nanograms/milliliter (ng/mL)

Measure	Child Pugh Class-A n = 6	Child Pugh Class-B n = 6	Child Pugh Class-C n = 6	Healthy Participants n = 12
Value	380 (44)	382 (23)	317 (65)	698 (30)

Population analysed: Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles).

Primary outcome: 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). Geometric mean (Geometric Coefficient of Variation). Unit: ng*hour (h)/mL

Measure	Child Pugh Class-A n = 6	Child Pugh Class-B n = 6	Child Pugh Class-C n = 6	Healthy Participants n = 12
Value	4151 (43)	4490 (38)	4534 (74)	7165 (24)

Population analysed: Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles).

Primary outcome: 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). Geometric mean (Geometric Coefficient of Variation). Unit: ng* h/mL

Measure	Child Pugh Class-A n = 6	Child Pugh Class-B n = 6	Child Pugh Class-C n = 6	Healthy Participants n = 12
Value	4174 (43)	4550 (39)	4649 (78)	7286 (25)

Population analysed: Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles).

Primary outcome: 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). Median (Full Range). Unit: hours

Measure	Child Pugh Class-A n = 6	Child Pugh Class-B n = 6	Child Pugh Class-C n = 6	Healthy Participants n = 12
Value	1.5 (1 to 2)	1.0 (1 to 4)	1.5 (1 to 4)	1.3 (1 to 2)

Population analysed: Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles).

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Child Pugh Class-A	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Child Pugh Class-B	0 of 6 (0%)	3 of 6 (50%)	Not reported
Child Pugh Class-C	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Healthy Participants	0 of 12 (0%)	2 of 12 (16.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bristol-Myers Squibb study director

Bristol-Myers Squibb

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BMS-790052 in people with Hepatic Insufficiency, run by Bristol-Myers Squibb at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00859053.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2015.