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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 7
- 主要终点
- Incidence of adverse events (AEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Active Treatment (BMS-963272) Dosing Regimen 1
干预措施: BMS-963272 (Drug)
Active Treatment (BMS-963272) Dosing Regimen 2
干预措施: BMS-963272 (Drug)
Placebo
干预措施: Placebo matching BMS-963272 (Other)
结局指标
主要结局
Incidence of adverse events (AEs)
时间窗: Up to 166 days
Incidence of clinically significant changes in physical examination findings
时间窗: Up to 166 days
Incidence of serious adverse events (SAEs)
时间窗: Up to 166 days
Incidence of clinically significant changes in vital signs: Blood pressure
时间窗: Up to 166 days
Incidence of clinically significant changes in vital signs: Heart rate
时间窗: Up to 166 days
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Up to 166 days
Incidence of clinically significant changes in clinical laboratory results: Hematology tests
时间窗: Up to 166 days
Incidence of clinically significant changes in clinical laboratory results: Coagulation tests
时间窗: Up to 166 days
Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
时间窗: Up to 46 days
Incidence of clinically significant changes in clinical laboratory results: Liver function tests
时间窗: Up to 166 days
Incidence of clinically significant changes in clinical laboratory results: Lipid panel tests
时间窗: Up to 166 days
次要结局
- Pharmacokinetic (PK) sampling: Maximum observed plasma concentration (Cmax)(Day 1 and Day 84)
- 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)