A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Multicenter Phase 2 Study to Evaluate the Safety, Efficacy, and Tolerability of MLS-101 in Subjects With Uncontrolled Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 44
- 主要终点
- Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo
研究概览
简要总结
A randomized, double-blind, placebo-controlled, dose-ranging, Phase II study to evaluate the safety, efficacy, and tolerability of MLS-101 in Subjects With Uncontrolled Hypertension
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and nonpregnant, nonlactating female subjects ≥ 18 years of age.
- •Written informed consent Health Insurance Portability and Accountability Act authorization, and local patient privacy required documentation for this study have been obtained
- •Automated office blood pressure (AOBP) with SBP ≥ 130 mm Hg
- •Background antihypertensive treatment of ≥ 2 drugs
- •Serum cortisol ≥ 18 mcg/dL
排除标准
- •Concomitant use of epithelial sodium channel inhibitors or mineralocorticoid receptor antagonists
- •Subjects with hypokalemia
- •Subjects with hyperkalemia
- •Subjects with serum cortisol < 3 mcg/dL
- •Subjects with serum sodium < 135 mEq/L
- •Subjects with estimated glomerular filtration rate < 60 mL/min/1.73m2
- •Subjects with type 1 or uncontrolled (hemoglobin A1c ≥ 9%) type 2 diabetes mellitus
- •Subjects with body mass index > 40 kg/m2
- •Subjects with unstable angina
- •Subjects with SBP ≥ 175 mm Hg or DBP ≥ 100 mm Hg for Part 1 and SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg for Part 2 at Pre-Screening, Screening/Start of Placebo Run-in, or Randomization
- •Subjects with a decrease in SBP ≥ 20 mm Hg or DBP ≥ 10 mm Hg from sitting to standing position at screening
- •Subjects who, in the opinion of the investigator, have suspected nonadherence to antihypertensive treatment
- •Subjects who, in the opinion of the investigator, have any major medical illness or symptoms
- •Subjects who, in the opinion of the investigator, have any acute or chronic medical or psychiatric condition
- •Subjects undergoing treatment with any of the following medications:
- •Topical corticoids
- •Sympathomimetic decongestants
- •Theophylline
- •Phosphodiesterase type 5 inhibitors
- •Intramuscular steroids
- •Cytochromes
- •Strong CYP3A and CYP3A4 inducers
- •Subjects with known hypersensitivity to MLS-101 or any of the excipients
- •Subjects who are night-shift workers
研究组 & 干预措施
Placebo (Part I)
Placebo tablet(s) by mouth once or twice daily.
干预措施: Placebo (Part I) (Other)
Dose 1 (Part I)
MLS-101 tablet(s) by mouth once or twice daily.
干预措施: MLS-101 (Part I) (Drug)
Dose 2 (Part I)
MLS-101 tablet(s) by mouth once or twice daily.
干预措施: MLS-101 (Part I) (Drug)
Dose 3 (Part I)
MLS-101 tablet(s) by mouth once or twice daily.
干预措施: MLS-101 (Part I) (Drug)
Placebo (Part II)
Placebo tablet(s) by mouth once daily.
干预措施: Placebo (Part II) (Other)
Dose (Part II)
MLS-101 tablet(s) by mouth once daily.
干预措施: MLS-101 (Part II) (Drug)
结局指标
主要结局
Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo
时间窗: 8 Weeks
The primary outcome was defined as the change in office-measured (mean of last 2 of 5 unattended measurements using an automated oscillometric sphygmomanometer device after approximately 5 minutes of rest in the seated position) SBP from baseline to the end of Study Week 8. The primary efficacy analysis was performed using a mixed model repeated measures (MMRM) approach with defined fixed effects per the statistical analysis plan. A least-square estimate of the mean difference between each dose group and the placebo group is provided for Week 8.
次要结局
- Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT)(8 Weeks)
- Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP)(8 weeks)
- Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8(8 Weeks)