A Randomized, Double Blind, Placebo Controlled, Multicenter, Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of HTD1801 in Adults With Hypercholesterolemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 5
- 主要终点
- Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, multicenter, multiple ascending dose (MAD) study to evaluate the safety and tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of HTD1801 in overweight to obese adults with hypercholesterolemia. There were 3 cohorts of dose levels as 500, 1000 and 2000 mg/day, with 16 subjects planned for each cohort randomized 3:1 to receive either HTD1801 or Placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have given written informed consent
- •Males or females aged 18 to 70 years old at the time of first dosing
- •Have a body mass index (BMI) of >25.0 and ≤ 45.0 kg/m2 at Screening
- •Have a documented history of hypercholesterolemia, defined as LDL-C ≥ 2.59 mmol/L
排除标准
- •The use of any anti-dyslipidemia agent within 28 days prior to dosing
- •History of a total cholesterol ≥ 10.35 mmol/L or triglyceride ≥ 11.3 mmol/L
- •History of a clinically significant cardiac arrhythmia or clinically significant abnormal ECG results at Screening
- •Significant peripheral or coronary vascular disease
- •Clinically significant abnormal blood pressure at Screening or Baseline, defined as supine blood pressure ≥160/100 mmHg, or ≤ 90/60 mmHg
- •Primary hypothyroidism (thyroid stimulating hormone [TSH] > upper limit or normal [ULN] and free T4 < lower limit of normal [LLN]), primary subclinical hypothyroidism (screening TSH > ULN and free T4 within normal limits [WNL]), or secondary hypothyroidism (screening TSH < LLN and free T4< LLN) at Screening
- •Glucose-6-phosphate dehydrogenase (G6PD) deficiency
研究组 & 干预措施
HTD1801 500 mg BID
Subjects received 1000 mg/day HTD1801
干预措施: HTD1801 Tablets, 1000 mg (Drug)
HTD1801 250 mg BID
Subjects received 500 mg/day HTD1801
干预措施: HTD1801 Tablets, 500 mg (Drug)
HTD1801 1000 mg BID
Subjects received 2000 mg/day HTD1801
干预措施: HTD1801 Tablets, 2000 mg (Drug)
Placebo
干预措施: Placebo to match 500 mg HTD1801 (Drug)
Placebo
干预措施: Placebo to match 1000 mg HTD1801 (Drug)
Placebo
干预措施: Placebo to match 2000 mg HTD1801 (Drug)
结局指标
主要结局
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
时间窗: 4 weeks
TEAEs are defined as any AEs that commenced on or after exposure to study drug or any pre-existing AE that worsened in either intensity or frequency after exposure to study drug.
次要结局
- Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration(0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28)
- Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration(0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1)
- Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups(Baseline, Day 14, Day 28)
- Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration(0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28)
- Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration(0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1)
- Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration(0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1)
- Plasma Half-life of HTD1801 Components (T1/2) After Multiple-dose Oral Administration(0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28)
- Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups(Baseline, Day 14, Day 28)
- Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups(Baseline, Day 14, Day 28)
- Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups(Baseline, Day 14, Day 28)