Efficacy and Safety of Lorundrostat in Subjects With Uncontrolled and Resistant Hypertension

Study Overview
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Brief Summary
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This is a Phase 3 trial to evaluate the BP-lowering effect of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled and resistant hypertension taking between 2 and 5 anti-hypertensive (AHT) medications.

Detailed Description
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This study is a Phase 3 trial to evaluate the BP-lowering effect of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled and resistant hypertension taking between 2 and 5 anti-hypertensive (AHT) medications, one of which must be a thiazide or thiazide-like diuretic. The study consists of a 2-week screening period with a 2-week single-blind placebo period followed by a 12-week randomized, double-blind, placebo-controlled, parallel arm period. Following the randomized period subjects will be offered an opportunity to participate in an open-label extension (OLE) study. Any subject electing to not participate in the OLE will undergo a 2-week end of study (EoS) visit, which will occur after end of treatment (EoT), to complete their participation in the study.

Official Title
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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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Placebo
* Drug: lorundrostat Dose 1
* Drug: lorundrostat Dose 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age at the time of signing the informed consent form (ICF) 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, History of hypertension lasting at least 6 months prior to Screening Body mass index (BMI) of ≥18 kg/m2 at Screening Exclusion Criteria: Women who are pregnant, plan to become pregnant, or are breastfeeding 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. History of heart failure, myocardial infarction, stroke, or transient ischemic attack within 6 months prior to the Screening Visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo once daily (QD) for 12 weeks | Drug: Placebo<br>* Placebo once daily (QD) for 12 weeks<br>|
| Experimental: Dose 1<br>50 mg lorundrostat Dose 1 once daily (QD) for 12 weeks | Drug: lorundrostat Dose 1<br>* 50 mg lorundrostat Dose 1 once daily (QD) for 12 weeks<br>|
| Experimental: Dose 2<br>50 mg lorundrostat Dose 1 once daily (QD) for 6 weeks then 100 mg lorundrostat Dose 2 once daily (QD) for 6 weeks for subjects who meet prespecified criteria | Drug: lorundrostat Dose 2<br>* 50 mg lorundrostat Dose 1 once daily (QD) for 6 weeks then 100 mg lorundrostat Dose 2 once daily (QD) for 6 weeks for subjects who meet prespecified criteria<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in automated office BP (AOBP) SBP at Week 12 in subjects randomized to lorundrostat |  | Week 12 | 
| Change from baseline in AOBP SBP at Week 12 in subjects randomized to lorundrostat Dose 1 with escalation to lorundrostat Dose 2 |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with AOBP SBP <130 mmHg at Week 12 in combined lorundrostat dosages |  | Week 12 | 
| Change from baseline in AOBP SBP at Week 12 in subjects with uncontrolled hypertension in combined lorundrostat dosages |  | Week 12 | 
| Change from baseline in AOBP SBP at Week 12 in subjects with resistant hypertension in combined lorundrostat dosages |  | Week 12 | 
| Change from baseline in AOBP SBP at Week 12 by obesity status in combined lorundrostat dosages |  | Week 12 | 
| Change from baseline in AOBP SBP at Week 12 in subjects who did not reach SBP control by Week 6 on lorundrostat Dose 1 and were increased to lorundrostat Dose 2 (within-subjects analysis) |  | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood pressure, Hypertension, Hypertensive, Resistant hypertension, Uncontrolled hypertension