A Placebo-Controlled, Double-Blind, Randomized Phase 2 Study to Evaluate the Effect of Obicetrapib in Combination With Ezetimibe in Participants With Mild Dyslipidemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 9
- 主要终点
- Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [Friedewald]
研究概览
简要总结
This study will be a placebo-controlled, double-blind, randomized, phase 2 study in participants with mild dyslipidemia to evaluate the efficacy, safety, and tolerability of obicetrapib and ezetimibe combination therapy.
详细描述
This study will be a placebo-controlled, double-blind, randomized, phase 2 study in participants with mild dyslipidemia to evaluate the efficacy, safety, and tolerability of obicetrapib and ezetimibe combination therapy. The screening period for this study will take up to 2 weeks. Following the screening period, eligible patients will be randomized to placebo, 5 mg obicetrapib + 10 mg ezetimibe; 5 mg obicetrapib + placebo ezetimibe; or placebo obicetrapib + 10 mg ezetimibe for an 8 week treatment period. After the treatment period, patients will continue for a 4 week safety follow-up and a 8 week PK follow-up.
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)
盲法说明
placebo tablet made to resemble active
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
- •Understanding of the study procedures, willingness to adhere to the study schedules and diet, and agreement to participate in the study by giving written informed consent prior to Screening procedures
- •Men or women 18 to 70 years of age, inclusive
- •Women may be enrolled if all 3 of the following criteria are met:
- •They are not pregnant;
- •They are not breastfeeding; and
- •They do not plan on becoming pregnant during the study
- •Women of childbearing potential must have a negative urine pregnancy test at the Screening Visit.
- •Women of childbearing potential must agree to use an effective method of avoiding pregnancy from the Screening Visit to 90 days after the last visit. Men whose partners are of childbearing potential must agree to use an effective method of avoiding pregnancy from the Screening Visit to 90 days after the last visit.
- •Fasting LDL-C levels >2.5 mmol/L (>100 mg/dL) and <4.5 mmol/L (<175 mg/dL) and TG levels <4.5 mmol/L (<400 mg/dL) (Visit 1) and
- •Willingness to maintain a stable diet and physical activity level throughout the study
排除标准
- •Body mass index >= 40 kg/m2
- •Participation in another clinical study involving an investigational or marketed drug within 30 days prior to the Screening Visit
- •Currently taking any lipid-altering therapy
- •Any clinical manifestation of atherosclerotic CVD or any evidence of ischemic coronary disease present on the 12-lead ECG at the Screening Visit
- •Diagnosis of type 1 or type 2 diabetes mellitus; or HbA1c >= 6.5% at the Screening visit if no prior diagnosis of diabetes mellitus
- •Uncontrolled hypertension ie, sitting systolic blood pressure >160 mmHg and/or sitting diastolic blood pressure >90 mmHg taken as the average of triplicate measurements.
- •One retest will be allowed, at which point if the retest result is no longer exclusionary, the participant may be randomized
- •Active muscle disease or persistent creatine kinase concentration >3 x the upper limit of normal (ULN). One retest will be allowed after 1 week to verify the result, at which point if the retest result is no longer exclusionary, the participant may be randomized
- •History of torsades de pointes
- •Estimated glomerular filtration rate <60 mL/min calculated using the Chronic Kidney Disease Epidemiology Collaboration equation
- •Hepatic dysfunction as evidenced by any laboratory abnormality as follows: gamma- glutamyl transferase, alanine aminotransferase, or aspartate aminotransferase >2 x ULN, or total bilirubin >1.5 x ULN
- •Anemia, defined as hemoglobin concentration <11 g/dL for males and hemoglobin concentration <9 g/dL for females
- •History of malignancy within the past 5 years, with the exception of non-melanoma skin cancers
- •Evidence of any other clinically significant non-cardiac disease or condition that, in the opinion of the Investigator, would preclude participation in the study
- •Known ezetimibe or CETP inhibitor allergy or intolerance
研究组 & 干预措施
Placebo
placebo obicetrapib + placebo ezetimibe; once daily
干预措施: Placebo (Other)
Combination therapy
5 mg obicetrapib + 10 mg ezetimibe; once daily
干预措施: Obicetrapib 5mg (Drug)
Combination therapy
5 mg obicetrapib + 10 mg ezetimibe; once daily
干预措施: Ezetimibe 10mg (Drug)
Obicetrapib monotherapy
5 mg obicetrapib + placebo ezetimibe; once daily
干预措施: Obicetrapib 5mg (Drug)
Ezetimibe monotherapy
placebo obicetrapib + 10 mg ezetimibe; once daily
干预措施: Ezetimibe 10mg (Drug)
结局指标
主要结局
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [Friedewald]
时间窗: 8 weeks
Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [Friedewald]
时间窗: 8 weeks
Median percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [Friedewald]
时间窗: 8 weeks
LS Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [PUC]
时间窗: 8 weeks
Mean percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [PUC]
时间窗: 8 weeks
Median percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [PUC]
时间窗: 8 weeks
LS Mean percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)
次要结局
- Median Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo(8 weeks)
- LS Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo(8 weeks)
- Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo(8 weeks)
- LS Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo(8 weeks)
- Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy [Friedewald](8 weeks)
- Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [PUC](8 weeks)
- Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [Friedewald](8 weeks)
- Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [Friedewald](8 weeks)
- Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [Friedewald](8 weeks)
- LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [Friedewald](8 weeks)
- Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [PUC](8 weeks)
- LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [PUC](8 weeks)
- Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo(8 weeks)
- Median Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo(8 weeks)
- Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy [Friedewald](8 weeks)
- LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy [Friedewald](8 weeks)
- Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Ezetimibe Monotherapy [Friedewald](8 weeks)
- Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Ezetimibe Monotherapy [Friedewald](8 weeks)
- LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Ezetimibe Monotherapy [Friedewald](8 weeks)
- Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [Friedewald](8 weeks)
- LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [Friedewald](8 weeks)
- Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [PUC](8 weeks)
- Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [PUC](8 weeks)
- LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [PUC](8 weeks)
- Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy(8 weeks)
- Median Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy(8 weeks)
- LS Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy(8 weeks)