Clinical trial NCT04766476: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Nonalcoholic Fatty Liver Disease
Keywords: BMS-963272
Liver Fibrosis
Nonalcoholic Fatty Liver Disease (NAFLD)
Nonalcoholic Steatohepatitis (NASH)
Phase 1b
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2021-02-23
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Up to 166 days
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in vital signs: Blood pressure
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in vital signs: Heart rate
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in physical examination findings
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry test
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in clinical laboratory results: Hematology tests
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in clinical laboratory results: Coagulation tests
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
timeFrame: Up to 46 days
measure: Incidence of clinically significant changes in clinical laboratory results: Liver function tests
timeFrame: Up to 166 days
measure: Incidence of clinically significant changes in clinical laboratory results: Lipid panel tests
timeFrame: Up to 166 days
Secondary outcomes:
measure: Pharmacokinetic (PK) sampling: Maximum observed plasma concentration (Cmax)
timeFrame: Day 1 and Day 84
measure: Pharmacokinetic (PK) sampling: Time to maximum observed plasma concentration (Tmax)
timeFrame: Day 1 and Day 84
measure: Pharmacokinetic (PK) sampling: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC [0-T])
timeFrame: Day 1 and Day 84
measure: Trough observed plasma concentration (Ctrough)
timeFrame: Day 1, Day 15, Day 29, Day 57, and Day 84
Other outcomes:
Locations:
city: Cullman
country: United States
facility: Cullman Clinical Trials
state: Alabama
city: Chandler
country: United States
facility: Local Institution
state: Arizona
city: Tucson
country: United States
facility: Arizona Liver Health - Tucson
state: Arizona
city: Boca Raton
country: United States
facility: Local Institution
state: Florida
city: Boynton Beach
country: United States
facility: RecioMed Clinical Research Network
state: Florida
city: Miami Lakes
country: United States
facility: Floridian Clinical Research
state: Florida
city: Miami
country: United States
facility: Local Institution
state: Florida
city: Miami
country: United States
facility: Advanced Pharma - Miami
state: Florida
city: Port Orange
country: United States
facility: Local Institution
state: Florida
city: Bastrop
country: United States
facility: Local Institution
state: Louisiana
city: Biloxi
country: United States
facility: Local Institution
state: Mississippi
city: Kansas City
country: United States
facility: Local Institution
state: Missouri
city: Chattanooga
country: United States
facility: Local Institution
state: Tennessee
city: Germantown
country: United States
facility: Local Institution
state: Tennessee
city: Austin
country: United States
facility: Pinnacle Clinical Research - Austin
state: Texas
city: Edinburg
country: United States
facility: Local Institution
state: Texas
city: McAllen
country: United States
facility: Local Institution
state: Texas
city: San Antonio
country: United States
facility: Local Institution
state: Texas
city: San Antonio
country: United States
facility: Local Institution
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: