Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to assess the effects of hepatic impairment on the single dose pharmacokinetics of BMS-790052.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BMS-790052 in Child-Pugh A | Active Comparator |
| |
| BMS-790052 in Child-Pugh B | Active Comparator |
| |
| BMS-790052 in Child-Pugh C | Active Comparator |
| |
| BMS-790052 in Healthy Subjects | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BMS-790052 | Drug | Capsules, Oral, 30 mg, single dose, one day |
|
| 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 |
| 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). |
Not provided
Key Inclusion Criteria:
Key Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Advanced Clinical Research Institute | Anaheim | California | 92801 | United States | ||
| Orlando Clinical Research Center |
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.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Analysis was done in safety population, defined as all the participants who received study medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Child Pugh Class-A | 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. |
| BG001 | Child Pugh Class-B |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles). | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms/milliliter (ng/mL) | 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) |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Child Pugh Class-A | 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bristol-Myers Squibb Study Director | Bristol-Myers Squibb | Clinical.Trials@bms.com |
Not provided
| ID | Term |
|---|---|
| D048550 | Hepatic Insufficiency |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C549273 | daclatasvir |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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) |
| Day 1 to end of study for AEs and, Day 1 to up to 30 days after last dose for SAE. |
| Orlando |
| Florida |
| 32809 |
| United States |
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.
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
|
|
| 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. | Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hour (h)/mL | 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) |
|
|
|
| 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/λ z, where λ z was the terminal elimination rate constant and Ct was the last observable concentration. | Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng* h/mL | 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) |
|
|
|
| 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. | Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles). | Posted | Median | Full Range | hours | 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) |
|
|
|
| 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. | Analysis was performed in the Pharmacokinetic population (all participants who received study drug and had adequate PK profiles). | Posted | Mean | Standard Deviation | hours | 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) |
|
|
|
| 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/λ z, where λ z was the terminal elimination rate constant and Ct was the last observable concentration. | Analysis was performed in PK set population. | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliter/minute (mL/min) | 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) |
|
|
|
| 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/ λz, where λz was the terminal elimination rate constant and Ct was the last observable concentration. | Analysis was performed in PK population. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | 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) |
|
|
|
| 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/λ z, where λ z was the terminal elimination rate constant and Ct was the last observable concentration. | Analysis was performed in PK population. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL | 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 | 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). | Analysis was done in safety population, defined as all the participants who received study medication. | Posted | Number | Participants | Day 1 to end of study for AEs and, Day 1 to up to 30 days after last dose for SAE. |
|
|
|
| 0 |
| 6 |
| 1 |
| 6 |
| EG001 | 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. | 0 | 6 | 3 | 6 |
| EG002 | 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. | 0 | 6 | 2 | 6 |
| EG003 | 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. | 0 | 12 | 2 | 12 |
| Malaise | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 12.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Cold sweat | Skin and subcutaneous tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
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.
| Death |
|
| Discontinuations due to AEs |
|