2023-506425-12-00已完成3 期
MLS-101-301: A Randomized, Double-Blind, Placebo Controlled, Parallel Arm, Multicenter Phase 3 Study to Evaluate the Efficacy and Safety of Lorundrostat in Subjects with Uncontrolled and Resistant Hypertension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 420
- 试验地点
- 72
- 主要终点
- Change from baseline in automated office BP (AOBP) SBP at Week 6 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo
研究概览
简要总结
To assess the effect of Lorundrostat when added to prescribed AHT on SBP in subjects with hypertension
研究设计
- 分配方式
- Randomized
- 主要目的
- Double-blind period
- 盲法
- Double (Carer, Analyst, Monitor, Investigator, Subject)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Written informed consent, obtained before any study-related assessment is performed
- •Willing and able to comply with the study instructions and attend all scheduled study visits
- •At least 18 years of age at the time of signing the informed consent form (ICF) and capable of providing informed consent
- •At Screening and Randomization: AOBP SBP of ≥135 and ≤180 mmHg plus AOBP DBP of ≥65 and ≤110 mmHg, or AOBP DBP of ≥90 and ≤110 mmHg
- •Taking between 2 and 5 AHT medications, inclusive, at a stable for at least four weeks dose for 1 month prior to the Screening Visit, of which one must be a thiazide or thiazide-like diuretic. If a subject is not on a thiazide or thiazide like diuretic at the Screening visit, the thiazide or thiazide-like diuretic medication may be initiated prior to, or at the start of the Run-in period and must remain stable until the Randomization visit, unless the medication is not tolerated by the subject or medically contraindicated. Inclusion of a thiazide or thiazide-like diuretic in the prescribed AHT regimen may be waived in these circumstances following discussion with the Medical Monitor. NOTE: MRAs and epithelial sodium channel (ENaC) inhibitors are not allowed. NOTE: each individual AHT agent in a combination pill counts as one AHT medication.
- •History of hypertension lasting at least 6 months prior to Screening
- •Serum cortisol (morning measurement, blood draw as close to 8 a.m. as possible but before 10 a.m.) between 3 and 22 µg/dL, inclusive, at Screening
- •Body mass index (BMI) of ≥18 kg/m2 at Screening
- •Arm circumference <52 centimeters at Screening
- •Fertile male subjects and female subjects of childbearing potential, and their partners, must agree to use either highly effective or acceptable methods of contraception from the Screening Visit to 28 days after the last dose of study drug
排除标准
- •Women who are pregnant, plan to become pregnant, or are breastfeeding
- •History of adrenal insufficiency or an abnormal ACTH stimulation test within 1 year prior to Screening.
- •History of white coat hypertension
- •Current, known or presumed orthostatic hypotension
- •Current, known or presumed autonomic dysfunction (e.g., neurally mediated [reflex] syncope, postural tachycardia syndrome)
- •Current night-shift worker, or anticipated to become a night-shift worker, defined as >14 days per month where work hours extend past midnight
- •Previously proven secondary cause of hypertension with the exception of documented sleep apnea.
- •History of heart failure, myocardial infarction, stroke, or transient ischemic attack within 6 months prior to the Screening Visit. Heart failure of New York Heart Association (NYHA) Class II or more requires approval of the Medical Monitor
- •Diabetes mellitus with a glycosylated hemoglobin (HbA1C) >9% (>74.9 mmol/mol) at Screening
- •Diabetes mellitus with >1 severe hypoglycemic event or severe diabetic ketoacidosis event (events requiring external help) in the 12 months prior to Screening, or with a history of impaired hypoglycemia awareness at Screening
- •Planned major surgery requiring hospitalization during the study period, or performed within 4 weeks prior to the Screening Visit
- •Subjects with known hypersensitivity to lorundrostat or any of the excipients
- •History of malignant neoplasms within the past 5 years prior to Screening, except known basal or squamous cell skin cancer, or any previously treated carcinoma in-situ
- •Treatment with MRAs and/or ENaC inhibitors within 1 month of the Screening Visit
- •Known or suspected abuse of illicit drugs or alcohol within 1 year prior to Screening
- •In the opinion of the Investigator, any other condition that will preclude participation in the study
- •Treatment, or anticipated treatment, with any prohibited medications within the timeframe described in this protocol
- •Participation in a study involving any investigational device or small-molecule drug within 4 weeks or 6 months for biologic (antibody) drugs prior to the Screening Visit
- •eGFR <45 mL/min/1.73m2 at Screening, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
- •Serum potassium >5.0 mmol/L at Screening or >4.8 mmol/L at Randomization
- •Serum sodium <135 mmol/L (corrected for hyperglycemia) at Screening. Rescreening of subjects with an exclusionary serum sodium requires 2 consecutive measurements at least one week apart of >135 mmol/L. A decrease in dose of a prescribed AHT diuretic prior to rescreening is allowed if, at the discretion of the Investigator, such adjustment would be safe and tolerable
- •History of clinically significant hyponatremia (requiring hospitalization, treatment, or associated with a sodium <130 mmol/L [corrected for glucose using the Katz formula]) or chronic and/or recurrent mild hyponatremia (sodium <135 mmol/L [corrected for glucose using the Katz formula]) within 1 year prior to Screening
- •Hospitalization for the treatment of urgent or emergent hypertension in subjects treated with at least 2 AHT medications within 1 year prior to Screening
结局指标
主要结局
Change from baseline in automated office BP (AOBP) SBP at Week 6 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo
Change from baseline in automated office BP (AOBP) SBP at Week 6 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo
次要结局
- Proportion of subjects with AOBP SBP <130 mmHg at Week 6 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo
- Change from baseline in AOBP SBP at Week 12 in subjects randomized to lorundrostat 50 mg QC with escalation to lorundrostat 100 mg QD compared to subjects randomized to placebo
- Change from baseline in AOBP SBP at Week 6 in subjects with uncontrolled hypertension on 2 prescribed AHT medications randomized to lorundrostat 50 mg QD compared to subjects with uncontrolled hypertension on 2 prescribed AHT medications randomized to placebo
- Change from baseline in AOBP SBP at Week 6 in subjects with uncontrolled hypertension on 3 or more prescribed AHT medications (resistant hypertension) randomized to lorundrostat 50 mg QD compared to subjects with uncontrolled hypertension on 3 or more prescribed AHT medications (resistant hypertension) randomized to placebo
- Change from baseline in AOBP SBP at Week 6 by obesity status in in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo
- Change from baseline in AOBP SBP at Week 12 in subjects who were escalated to lorundrostat 100 mg QD at Week 6 (within-subjects analysis)
研究者
David Rodman
Scientific
Mineralys Therapeutics Inc.
研究点 (72)
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