A Pivotal Study to Evaluate the Efficacy of Lorundrostat in Subjects With Uncontrolled Hypertension on a Standardized Antihypertensive Medication Regimen

Study Overview
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Brief Summary
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a Phase 2 trial to evaluate the blood pressure-lowering effect of lorundrostat (an aldosterone synthase inhibitor), administered on a background of a standardized anti-hypertensive (AHT) medication regimen, in subjects with uncontrolled and/or treatment-resistant hypertension.

Detailed Description
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This study is a Phase 2 trial to evaluate the blood pressure-lowering effects of lorundrostat (an aldosterone synthase inhibitor), administered on a background of a standardized anti-hypertensive (AHT) medication regimen, in subjects with uncontrolled and/or treatment-resistant hypertension. The study consists of a standardized AHT regimen run-in phase followed by a randomized, double-blind, placebo-controlled, parallel arm phase, after which subjects will enter a washout period ending with an end of study (EoS) visit. Subjects may be offered the opportunity to participate in an open-label extension (OLE). Any subject electing to not participate in the OLE will undergo an end of study (EoS) visit to complete their participation in the study. The study will be conducted at approximately 75-100 sites across the United States.

Official Title
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A Randomized, Double-Blind, Placebo Controlled, Parallel Arm, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Lorundrostat in Subjects With Uncontrolled Hypertension on a Standardized Medication Regimen

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 At Screening: AOBP SBP of 140-180 mmHg and AOBP DBP of 65-110 mmHg, or AOBP DBP of 90-110 mmHg 24-hour average ABPM SBP of 130-180 mmHg or 24-hour average ABPM DBP >80 mmHg Taking between 2 and 5 AHT medications, inclusive, at Screening visit. BMI of 18-40 kg/m2 inclusive at Screening Exclusion Criteria: eGFR <45 mL/min/1.73 m2 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 at Screening History of heart failure, myocardial infarction, stroke, or transient ischemic attack within 6 months prior to Screening. Diabetes mellitus with a glycosylated hemoglobin (HbA1c) >9% (>74.9 mmol/mol) at Screening

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 for 12 weeks | Drug: Placebo<br>* Placebo once daily for 12 weeks<br>|
| Experimental: Dose 1<br>lorundrostat Dose 1 once daily for 12 weeks | Drug: lorundrostat Dose 1<br>* lorundrostat Dose 1 once daily for 12 weeks<br>|
| Experimental: Dose 2<br>lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks | Drug: lorundrostat Dose 2<br>* lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 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 in 24-hour average ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP |  | Baseline (Randomization) to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-hour average ABPM SBP from baseline to Week 12, by body mass index (BMI) |  | Baseline to Week 12 | 
| Proportion of subjects with 24-hour average ABPM SBP <125 mmHg |  | at Week 12 | 
| Change in daytime average ABPM SBP |  | Baseline to Week 12 | 
| Change in automated office blood pressure (AOBP) SBP |  | Baseline to Week 12 | 
| Change in nighttime average ABPM SBP |  | Baseline to Week 12 | 
| Change in AOBP SBP |  | Baseline to Week 16 | 
| Change in 24-hour average ABPM SBP from baseline to Week 12, by number of AHT medications in the standardized AHT regimen (2 vs 3) |  | Baseline to Week 12 | 

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