Back to resultsA Study to Evaluate the Safety, Tolerability, and Drug Levels of BMS-963272 in Participants With Nonalcoholic Fatty Liver Disease
Primary Purpose
Nonalcoholic Fatty Liver Disease
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BMS-963272
Placebo matching BMS-963272
Sponsored by
About this trial
This is an interventional treatment trial for Nonalcoholic Fatty Liver Disease focused on measuring BMS-963272, Liver Fibrosis, Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH), Phase 1b
Eligibility Criteria
Inclusion Criteria:
- Body mass index (BMI) ≥ 30 kg/m^2
- Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 10% as evaluated by central review
- FibroScan-based transient elastography ≥ 9.9 kPa
- Alanine aminotransferase (ALT): > 30 U/L
- If available, historical diagnosis of non-alcoholic steatohepatitis (NASH) according to NASH Clinical Research Network classification by liver biopsy within 6 months before screening will be recorded
- Must agree to follow specific methods of contraception, if applicable
Exclusion Criteria:
- Women who are breastfeeding
- Inability to tolerate the mixed meal or the testing conditions, oral medication, venipuncture and/or inadequate venous access
- History or current diagnosis of cirrhosis, hepatocellular carcinoma (HCC), or hepatic decompensation
- Recent history (within 2 years before screening) of drug or alcohol abuse or excessive alcohol intake, defined as 30 g/day (men) or 20 g/day (women)
- Use of lipase inhibitors such as orlistat within 4 weeks before screening or during screening
- Use of glucagon-like peptide-1 (GLP-1) receptor agonists within 12 weeks before screening or during screening
- Uncontrolled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg) during screening, unless discussed with the Medical Monitor
- Glycated hemoglobin (HbA1c) ≥ 9.5%
- NASH-modifying therapies including investigational therapies (e.g., obeticholic acid, ursodeoxycholic acid) within 90 days before screening or during screening
- Medications for obesity within 12 weeks before screening, or during screening
- If taking vitamin E at a dose ≥ 800 mg/day, the dose must be stable beginning at least 6 months before screening and should remain stable during screening
- If taking a thiazolidinedione, the dose must be stable beginning at least 12 weeks before screening and should remain stable during screening
- If taking a dipeptidyl peptidase (DPP)-4 inhibitor or other medications for diabetes, the dose must be stable beginning at least 12 weeks before screening and should remain stable during screening
- If taking insulin, the dose may be altered by up to 10% within 12 weeks before screening and during the screening period
- If taking a statin or other prescription or over-the-counter lipid-lowering drug, the dose must be stable beginning at least 6 weeks before screening and should remain stable during screening
Other protocol-defined inclusion/exclusion criteria apply
Sites / Locations
- Cullman Clinical Trials
- Local Institution
- Arizona Liver Health - Tucson
- Local Institution
- RecioMed Clinical Research Network
- Floridian Clinical Research
- Local Institution
- Advanced Pharma - Miami
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Pinnacle Clinical Research - Austin
- Local Institution
- Local Institution
- Local Institution
- Local Institution
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Active Treatment (BMS-963272) Dosing Regimen 1
Active Treatment (BMS-963272) Dosing Regimen 2
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Incidence of adverse events (AEs)
Incidence of serious adverse events (SAEs)
Incidence of clinically significant changes in vital signs: Blood pressure
Incidence of clinically significant changes in vital signs: Heart rate
Incidence of clinically significant changes in physical examination findings
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval
PR interval: The time from the onset of the P wave to the start of the QRS complex
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval
QRS interval: A combination of the Q wave, R wave and S wave, the "QRS complex" represents ventricular depolarization
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval
QT interval: Measured from the beginning of the QRS complex to the end of the T wave
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval
QTcF interval: Corrected QT interval using Fridericia's formula (QTcF)
Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry test
Incidence of clinically significant changes in clinical laboratory results: Hematology tests
Incidence of clinically significant changes in clinical laboratory results: Coagulation tests
Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
Incidence of clinically significant changes in clinical laboratory results: Liver function tests
Incidence of clinically significant changes in clinical laboratory results: Lipid panel tests
Secondary Outcome Measures
Pharmacokinetic (PK) sampling: Maximum observed plasma concentration (Cmax)
Pharmacokinetic (PK) sampling: Time to maximum observed plasma concentration (Tmax)
Pharmacokinetic (PK) sampling: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC [0-T])
Trough observed plasma concentration (Ctrough)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04766476
Brief Title
A Study to Evaluate the Safety, Tolerability, and Drug Levels of BMS-963272 in Participants With Nonalcoholic Fatty Liver Disease
Official Title
A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 1b Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BMS-963272 in Participants With Nonalcoholic Fatty Liver Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Terminated
Why Stopped
Business objectives have changed
Study Start Date
February 24, 2021 (Actual)
Primary Completion Date
August 12, 2021 (Actual)
Study Completion Date
August 12, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and drug levels of BMS-963272 compared to placebo in participants with nonalcoholic fatty liver disease (NAFLD) and high probability of advanced fibrosis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Fatty Liver Disease
Keywords
BMS-963272, Liver Fibrosis, Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH), Phase 1b
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active Treatment (BMS-963272) Dosing Regimen 1
Arm Type
Experimental
Arm Title
Active Treatment (BMS-963272) Dosing Regimen 2
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
BMS-963272
Intervention Description
Specified dose on specified days
Intervention Type
Other
Intervention Name(s)
Placebo matching BMS-963272
Intervention Description
Specified dose on specified days
Primary Outcome Measure Information:
Title
Incidence of adverse events (AEs)
Time Frame
Up to 166 days
Title
Incidence of serious adverse events (SAEs)
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in vital signs: Blood pressure
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in vital signs: Heart rate
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in physical examination findings
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval
Description
PR interval: The time from the onset of the P wave to the start of the QRS complex
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval
Description
QRS interval: A combination of the Q wave, R wave and S wave, the "QRS complex" represents ventricular depolarization
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval
Description
QT interval: Measured from the beginning of the QRS complex to the end of the T wave
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval
Description
QTcF interval: Corrected QT interval using Fridericia's formula (QTcF)
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry test
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in clinical laboratory results: Hematology tests
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in clinical laboratory results: Coagulation tests
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
Time Frame
Up to 46 days
Title
Incidence of clinically significant changes in clinical laboratory results: Liver function tests
Time Frame
Up to 166 days
Title
Incidence of clinically significant changes in clinical laboratory results: Lipid panel tests
Time Frame
Up to 166 days
Secondary Outcome Measure Information:
Title
Pharmacokinetic (PK) sampling: Maximum observed plasma concentration (Cmax)
Time Frame
Day 1 and Day 84
Title
Pharmacokinetic (PK) sampling: Time to maximum observed plasma concentration (Tmax)
Time Frame
Day 1 and Day 84
Title
Pharmacokinetic (PK) sampling: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC [0-T])
Time Frame
Day 1 and Day 84
Title
Trough observed plasma concentration (Ctrough)
Time Frame
Day 1, Day 15, Day 29, Day 57, and Day 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Body mass index (BMI) ≥ 30 kg/m^2
Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 10% as evaluated by central review
FibroScan-based transient elastography ≥ 9.9 kPa
Alanine aminotransferase (ALT): > 30 U/L
If available, historical diagnosis of non-alcoholic steatohepatitis (NASH) according to NASH Clinical Research Network classification by liver biopsy within 6 months before screening will be recorded
Must agree to follow specific methods of contraception, if applicable
Exclusion Criteria:
Women who are breastfeeding
Inability to tolerate the mixed meal or the testing conditions, oral medication, venipuncture and/or inadequate venous access
History or current diagnosis of cirrhosis, hepatocellular carcinoma (HCC), or hepatic decompensation
Recent history (within 2 years before screening) of drug or alcohol abuse or excessive alcohol intake, defined as 30 g/day (men) or 20 g/day (women)
Use of lipase inhibitors such as orlistat within 4 weeks before screening or during screening
Use of glucagon-like peptide-1 (GLP-1) receptor agonists within 12 weeks before screening or during screening
Uncontrolled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg) during screening, unless discussed with the Medical Monitor
Glycated hemoglobin (HbA1c) ≥ 9.5%
NASH-modifying therapies including investigational therapies (e.g., obeticholic acid, ursodeoxycholic acid) within 90 days before screening or during screening
Medications for obesity within 12 weeks before screening, or during screening
If taking vitamin E at a dose ≥ 800 mg/day, the dose must be stable beginning at least 6 months before screening and should remain stable during screening
If taking a thiazolidinedione, the dose must be stable beginning at least 12 weeks before screening and should remain stable during screening
If taking a dipeptidyl peptidase (DPP)-4 inhibitor or other medications for diabetes, the dose must be stable beginning at least 12 weeks before screening and should remain stable during screening
If taking insulin, the dose may be altered by up to 10% within 12 weeks before screening and during the screening period
If taking a statin or other prescription or over-the-counter lipid-lowering drug, the dose must be stable beginning at least 6 weeks before screening and should remain stable during screening
Other protocol-defined inclusion/exclusion criteria apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Cullman Clinical Trials
City
Cullman
State/Province
Alabama
ZIP/Postal Code
35055
Country
United States
Facility Name
Local Institution
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
Arizona Liver Health - Tucson
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85712
Country
United States
Facility Name
Local Institution
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33434
Country
United States
Facility Name
RecioMed Clinical Research Network
City
Boynton Beach
State/Province
Florida
ZIP/Postal Code
33472
Country
United States
Facility Name
Floridian Clinical Research
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Facility Name
Local Institution
City
Miami
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
Advanced Pharma - Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33147
Country
United States
Facility Name
Local Institution
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
Local Institution
City
Bastrop
State/Province
Louisiana
ZIP/Postal Code
71220
Country
United States
Facility Name
Local Institution
City
Biloxi
State/Province
Mississippi
ZIP/Postal Code
39532
Country
United States
Facility Name
Local Institution
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
Local Institution
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37421
Country
United States
Facility Name
Local Institution
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Pinnacle Clinical Research - Austin
City
Austin
State/Province
Texas
ZIP/Postal Code
78757
Country
United States
Facility Name
Local Institution
City
Edinburg
State/Province
Texas
ZIP/Postal Code
78539
Country
United States
Facility Name
Local Institution
City
McAllen
State/Province
Texas
ZIP/Postal Code
78504
Country
United States
Facility Name
Local Institution
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Local Institution
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
Investigator Inquiry Form
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls
Learn more about this trial
A Study to Evaluate the Safety, Tolerability, and Drug Levels of BMS-963272 in Participants With Nonalcoholic Fatty Liver Disease
We'll reach out to this number within 24 hrs