A 2-Part, Phase 1, Single and Multiple Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of CAT-2054 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 118
- 试验地点
- 1
- 主要终点
- Frequency and severity of adverse events
研究概览
简要总结
This is a 2-part, Phase 1, placebo-controlled, double-blind, randomized, single and multiple ascending dose study. CAT-2054 will be administered either as an uncoated capsule (CAT-2054) or a coated capsule (CAT-2054-C). In Part A, CAT-2054 or placebo is administered as a single dose in a fasting state at 4 dose levels; at 3 dose levels, subjects will return for a second dose of the study drug after a high-fat meal. Additionally, at 1 dose level, CAT-2054-C or placebo will be administered as a single dose in a fasting state, and subjects will return for a second dose of the study drug after a high-fat meal. In Part B, CAT-2054 will be administered as multiple ascending doses at 4 dose levels for 14 consecutive days. In selected cohorts, CAT-2054, CAT-2054-C or CAT-2054 with atorvastatin will be dosed to assess safety in anticipation of future clinical trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provision of written informed consent before any study-specific procedure
- •Good health as determined by medical history, physical examination, vital sign measurements, ECG, and clinical laboratory measurements
- •Satisfies one of the following:
- •Females not of childbearing potential: non-pregnant and non-lactating surgically sterile or postmenopausal 2 years or less with a follicle-stimulating hormone assessment greater than or equal to 40 IU/L
- •Males: surgically sterile, abstinent, or subject or partner is utilizing an acceptable contraceptive method during and 3 months after the last study dose
- •For Part B only, measured at Screening: Fasting LDL-C ≥100 mg/dL; or (Cohort B6 only) fasting LDL-C ≥130 mg/dL
- •Body mass index (BMI) between 18 and 30 kg/m², inclusive, for Part A and between 18 and 40 kg/m², inclusive, for Part B, and body weight >50 kg at Screening
排除标准
- •Use of prescription drugs or non-prescription drugs including herbals, and dietary supplements (including multivitamins and any product containing niacin or omega-3 fatty acids above the Recommended Daily Allowance) within 2 weeks before dosing. Additionally for Part B only, use of any lipid-regulating prescription drug, non-prescription drug, herbal, or dietary supplement within 6 weeks before dosing
- •Clinically significant disease that requires a physician's care and/or would interfere with study evaluations
- •Clinically significant electrocardiogram (ECG) abnormalities or laboratory results as assessed by the investigator, such as QTcF >450
- •Use of any investigational drug or participation in any investigational study within 30 days prior to screening or 5 half-lives of the study agent, whichever is longer
研究组 & 干预措施
Cohort A1, Dose Level 1: CAT-2054 or placebo fasting
Single dose
干预措施: CAT-2054 (Drug)
Cohort A1, Dose Level 1: CAT-2054 or placebo fasting
Single dose
干预措施: Placebo (Drug)
Cohort A2, Dose Level 2: CAT-2054 or placebo fasting and fed
Single dose
干预措施: CAT-2054 (Drug)
Cohort A2, Dose Level 2: CAT-2054 or placebo fasting and fed
Single dose
干预措施: Placebo (Drug)
Cohort A3, Dose Level 3: CAT-2054 or placebo fasting and fed
Single dose
干预措施: CAT-2054 (Drug)
Cohort A3, Dose Level 3: CAT-2054 or placebo fasting and fed
Single dose
干预措施: Placebo (Drug)
Cohort A4, Dose Level 4: CAT-2054 or placebo fasting and fed
Single dose
干预措施: CAT-2054 (Drug)
Cohort A4, Dose Level 4: CAT-2054 or placebo fasting and fed
Single dose
干预措施: Placebo (Drug)
Cohort A5, Dose Level 5: CAT-2054-C or placebo fasting and fed
Single dose
干预措施: Placebo (Drug)
Cohort A5, Dose Level 5: CAT-2054-C or placebo fasting and fed
Single dose
干预措施: CAT-2054-C (Drug)
Cohort B1, Dose Level 1: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: CAT-2054 (Drug)
Cohort B1, Dose Level 1: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: Placebo (Drug)
Cohort B2, Dose Level 2: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: CAT-2054 (Drug)
Cohort B2, Dose Level 2: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: Placebo (Drug)
Cohort B3, Dose Level 3: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: CAT-2054 (Drug)
Cohort B3, Dose Level 3: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: Placebo (Drug)
Cohort B4, Dose Level 4: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: CAT-2054 (Drug)
Cohort B4, Dose Level 4: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: Placebo (Drug)
Cohort B5, Dose Level 5: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: CAT-2054 (Drug)
Cohort B5, Dose Level 5: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: Placebo (Drug)
Cohort B6, Dose Level 6: CAT-2054 with atorvastatin
Multiple dose for 14 days
干预措施: CAT-2054 (Drug)
Cohort B6, Dose Level 6: CAT-2054 with atorvastatin
Multiple dose for 14 days
干预措施: Atorvastatin (Drug)
Cohort B7, Dose Level 7: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: CAT-2054 (Drug)
Cohort B7, Dose Level 7: CAT-2054 or placebo
Multiple dose for 14 days
干预措施: Placebo (Drug)
结局指标
主要结局
Frequency and severity of adverse events
时间窗: up to 3 weeks
次要结局
- Changes from baseline for hematology, chemistry, coagulation and urinalysis(up to 3 weeks)
- AUCinf of CAT-2054(Days 1 through 4)
- Cmax of CAT-2054(up to 3 weeks)
- Assess the pharmacodynamic effects of multiple doses of CAT-2054 on serum lipids LDL-C, non-HDL-C, total cholesterol, triglycerides, HDL-C, apoB, and PCSK9.(up to 3 weeks)
- AUC48 of Atorvastatin(up to 3 weeks)