A Phase 1, Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial of LY3885125 to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Ascending Dose in Participants With Dyslipidemia and Repeat-Doses in Participants With NAFLD
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 49
- 试验地点
- 2
- 主要终点
- Part A: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
研究概览
简要总结
The main purpose of this study is to evaluate the safety and tolerability of LY3885125 after administration of single ascending doses in participants with dyslipidemia (part A) and multiple doses in participants with non-alcoholic fatty liver disease (part B). Blood tests will be performed to check how much LY3885125 gets into the bloodstream and how long it takes the body to eliminate it.
The study will last up to approximately 49 weeks for part A and 62 weeks for part B, for a total of approximately 111 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parts A & B
- •Males, or females of not of childbearing potential,
- •On a stable diet for the 3 months prior to randomization and willing to continue the same stable diet during the study.
- •Dyslipidemia with the following fasted blood levels at screening: 150 mg/dL ≤ triglycerides <500 mg/dL, AND LDL-cholesterol ≥100 mg/dL,
- •Body mass index (BMI) in range of 18.5 to 45.0 kg/m
- •NAFLD with liver fat content ≥8% as determined by magnetic resonance imaging proton density fat fraction (MRI-PDFF),
- •BMI in range of 27 to 45.0 kg/m2
排除标准
- •Parts A & B
- •History or presence of medical illness including, but not limited to, any cardiovascular, thromboembolism or bleeding disorder, hepatic, respiratory, hematological, endocrine, immune, psychiatric, or neurological disease, convulsions, or any clinically significant laboratory abnormality that, in the judgment of the Investigator, indicate a medical problem that would preclude study participation,
- •Uncontrolled hypertension with a resting blood pressure ≥ 160 mmHg systolic or ≥ 100 mmHg diastolic at visit 1,
- •Alanine transaminase (ALT) or aspartate aminotransferase (AST) >3.0 × ULN for the reference range,
- •Alkaline phosphatase (ALP) >1.5 × ULN for the reference range,
- •Total bilirubin (TBL) >1.5 × ULN for the reference range,
- •Taken drugs associated with hepatic steatosis (e.g., amiodarone, valproic acid, methotrexate, tamoxifen) for more than 2 weeks in the 3 months prior to screening visit,
- •Type 1 diabetes mellitus (T1DM) or any other type of diabetes mellitus other than T2DM,
- •Poorly controlled T2DM with glycated hemoglobin (HbA1c) of >9.0%,
- •Treatment with GLP-1 RA and GIP/GLP-1 RA and approved or experimental agents that target PCSK9 within 9 months prior to screening visit.
- •Evidence of other forms of chronic liver disease,
- •Initiated treatment with, or changed dose of, medications that may cause significant weight gain or weight loss, within 3 months prior to the screening visit,
- •Have a self-reported change in body weight >5 kg (11 pounds) within 3 months prior to screening visit
研究组 & 干预措施
Placebo (Part A)
Placebo administered SC
干预措施: Placebo (Drug)
Placebo (Part B)
Placebo administered SC
干预措施: Placebo (Drug)
LY3885125 (Part A)
Single ascending doses of LY3885125 administered subcutaneously (SC)
干预措施: LY3885125 (Drug)
LY3885125 (Part B)
Repeat doses of LY3885125 administered SC
干预措施: LY3885125 (Drug)
结局指标
主要结局
Part A: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Baseline up to 49 weeks (Part A)
Part A: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
Part B: Number of Participants with One or More SAEs Considered by the Investigator to be Related to Study Drug Administration
时间窗: Baseline up to 62 weeks (Part B)
Part B: A summary of SAEs and other non-serious AEs, regardless of causality, will be reported in the Reported Adverse Events module
Part A: Number of Participants With One or More Serious Adverse Event(s) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Baseline up to 36 weeks (Part A)
Part A: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
Part B: Number of Participants With One or More SAEs Considered by the Investigator to be Related to Study Drug Administration
时间窗: Baseline up to 36 weeks (Part B)
Part B: A summary of SAEs and other non-serious AEs, regardless of causality, will be reported in the Reported Adverse Events module
次要结局
- Part A & B: PK: Time of Maximum Observed Concentration (Tmax) of LY3885125(Baseline up to 49 weeks (Part A) and Baseline up to 62 weeks (Part B))
- Part A & B: PD: Change From Baseline in apolipoprotein B (ApoB)(Baseline up to 49 weeks (Part A) and Baseline up to 62 weeks (Part B))
- Part A & B: PK: Maximum Observed Plasma Concentration (Cmax) of LY3885125(Baseline up to 49 weeks (Part A) and Baseline up to 62 weeks (Part B))
- Part A & B: Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of LY3885125(Baseline up to 49 weeks (Part A) and Baseline up to 62 weeks (Part B))
- Part A & B: Pharmacodynamics (PD): Change From Baseline in Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9)(Baseline up to 49 weeks (Part A) and Baseline up to 62 weeks (Part B))
- Part B only: PD: Change of Liver Fat Content From Baseline by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF)(Baseline up to 62 weeks (Part B))
- Part A: Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of LY3885125(Baseline up to 36 weeks (Part A))
- Part A: PK: Maximum Observed Plasma Concentration (Cmax) of LY3885125(Baseline up to 36 weeks (Part A))
- Part A: PK: Time of Maximum Observed Concentration (Tmax) of LY3885125(Baseline up to 36 weeks (Part A))
- Part A: Pharmacodynamics (PD): Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)(Baseline up to Day 169 (Part A))
- Part A: PD: Change From Baseline in Apolipoprotein B (ApoB)(Baseline up to Day 169 (Part A))
- Part B Only: PD: Change of Liver Fat Content From Baseline by MRI-PDFF(Baseline up to 62 weeks (Part B))