Open-Label Extension Study to Assess Safety, Efficacy, and Tolerability of Lorundrostat in Subjects With Uncontrolled Hypertension

Study Overview
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Brief Summary
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This study is to evaluate the long-term safety, efficacy and tolerability of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled hypertension.

Detailed Description
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This study is to evaluate the long-term safety, efficacy and tolerability of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled hypertension. The study consists of an open-label dose treatment period of 48 weeks, followed by a 4-week double-blind randomized treatment withdrawal sub-study. The study will conclude with a 2-week wash-out period. To be eligible, subjects must complete the double-blind treatment phase of a respective parent study (including, but not limited to MLS-101-202 and MLS-101-301) and agree to transition immediately to this open-label extension (OLE) study (ie, will not participate in the end of study observation period of the parent study). The study will be conducted at approximately 200 centers.

Official Title
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An Open-Label Extension Study to Assess the Long-Term Safety, Efficacy, and Tolerability of Lorundrostat in Subjects With Uncontrolled Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: lorundrostat
* Drug: lorundrostat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent signed by the participant, obtained before any study-related assessment is performed At least 18 years of age at the time of signing the informed consent form Participation in a lorundrostat study with the option of transitioning to the OLE study Fertile male subjects and female subjects of childbearing potential, and their partners, must agree to use an acceptable method of contraception from study entry to 28 days after the last dose of study drug Willing and able to comply with the study instructions and attend all scheduled study visits [Randomized treatment withdrawal only] A minimum of 75% and a maximum of 125% compliance with lorundrostat from Week 32 to Week 48 of the OLE [Randomized treatment withdrawal only] Taking an oral dose of lorundrostat of at least 25 mg once daily Exclusion Criteria: Women who are pregnant, plan to become pregnant, or are breast-feeding In the opinion of the principal investigator, any other condition that will preclude participation in the study

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
Interventional Model Description: Double
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-Label Arm<br>lorundrostat once daily for 48 weeks | Drug: lorundrostat<br>* lorundrostat once daily for 48 weeks<br>|
| Experimental: Maintenance Arm<br>lorundrostat once daily for 4 weeks in the double-blind randomized treatment withdrawal sub-study | Drug: lorundrostat<br>* lorundrostat once daily for 4 weeks<br>|
| Experimental: Taper Arm<br>lorundrostat and/or placebo once daily for 4 weeks in the double-blind randomized treatment withdrawal sub-study | Drug: lorundrostat<br>* lorundrostat once daily for 4 weeks<br>Drug: Placebo<br>* Placebo once daily for 4 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo once daily for 4 weeks in the double-blind randomized treatment withdrawal sub-study | Drug: Placebo<br>* Placebo once daily for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in automated office blood pressure (AOBP) systolic blood pressure (SBP) |  | Week 16 to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AOBP SBP in subjects taking lorundrostat at study entry |  | Week 0 - 48 | 
| Change in AOBP SBP in subjects taking placebo at study entry |  | Week 16 - 48 | 
| Change in AOBP diastolic blood pressure (DBP) in subjects taking lorundrostat at study entry |  | Week 0 - 48 | 
| Change in AOBP DBP in subjects taking placebo at study entry |  | Week 16 - 48 | 
| Proportion of subjects with AOBP SBP ≤130 mmHg at each visit |  | Through study completion, up to 54 weeks | 
| Proportion of subjects with AOBP ≤130/80 mmHg at each visit |  | Through study completion, up to 54 weeks | 
| In subjects participating in the randomized withdrawal sub-study, change in AOBP SBP |  | Week 48 to Week 52 | 
| In subjects participating in the randomized withdrawal sub-study, change in AOBP DBP |  | Week 48 to Week 52 | 

 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