Nonalcoholic Fatty Liver Disease
Conditions
Keywords
BMS-963272, Liver Fibrosis, Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH), Phase 1b
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.
Interventions
DRUGBMS-963272
Specified dose on specified days
OTHERPlacebo matching BMS-963272
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of clinically significant changes in clinical laboratory results: Lipid panel tests | Up to 166 days | — |
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests | Up to 166 days | — |
| Incidence of clinically significant changes in clinical laboratory results: Coagulation tests | Up to 166 days | — |
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests | Up to 46 days | — |
| Incidence of clinically significant changes in clinical laboratory results: Liver function tests | Up to 166 days | — |
| Incidence of adverse events (AEs) | Up to 166 days | — |
| Incidence of serious adverse events (SAEs) | Up to 166 days | — |
| Incidence of clinically significant changes in vital signs: Blood pressure | Up to 166 days | — |
| Incidence of clinically significant changes in vital signs: Heart rate | Up to 166 days | — |
| Incidence of clinically significant changes in physical examination findings | Up to 166 days | — |
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval | Up to 166 days | 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 | Up to 166 days | 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 | Up to 166 days | 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 | Up to 166 days | QTcF interval: Corrected QT interval using Fridericia's formula (QTcF) |
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry test | Up to 166 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) sampling: Time to maximum observed plasma concentration (Tmax) | Day 1 and Day 84 |
| Pharmacokinetic (PK) sampling: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC [0-T]) | Day 1 and Day 84 |
| Trough observed plasma concentration (Ctrough) | Day 1, Day 15, Day 29, Day 57, and Day 84 |
| Pharmacokinetic (PK) sampling: Maximum observed plasma concentration (Cmax) | Day 1 and Day 84 |
Countries
United States
Outcome results
None listed