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

Phase 2
Completed
Conditions
Hypertension
Interventions
Drug: lorundrostat Dose 2
Drug: lorundrostat Dose 1
Drug: Placebo
Registration Number
NCT05769608
Lead Sponsor
Mineralys Therapeutics Inc.
Brief Summary

A Phase 2 trial to evaluate the blood pressure-lowering effect of lorundrostat an aldosterone synthase inhibitor (ASI), administered as an add-on to a standardized anti-hypertensive (AHT) medication regimen, in subjects with hypertension.

Detailed Description

This study is a Phase 2 trial to evaluate the blood pressure-lowering effects of lorundrostat (an ASI), administered as add-on to a standardized anti-hypertensive (AHT) medication regimen, in subjects with hypertension.

The study consists of a standardized AHT regimen run-in period followed by a randomized, double-blind, placebo-controlled, parallel arm period. Following the double-blind period subjects may be offered the opportunity to participate in an open-label extension (OLE) study. Subjects electing to not participate in the OLE will undergo an end of study (EoS) visit approximately 2 weeks after the last dose of study drug to complete their participation in the study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
285
Inclusion Criteria
  1. At least 18 years of age at the time of signing the informed consent form
  2. At Screening: AOBP SBP of 140-180 mmHg and AOBP DBP of 65-110 mmHg, or AOBP DBP of 90-110 mmHg
  3. 24-hour average ABPM SBP of 130-180 mmHg or 24-hour average ABPM DBP >80 mmHg
  4. Taking between 2 and 5 AHT medications, inclusive, at Screening visit.
  5. BMI of 18-40 kg/m2 inclusive at Screening
Exclusion Criteria
  1. eGFR <45 mL/min/1.73 m2 at Screening, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
  2. Serum potassium >5.0 mmol/L at Screening or >4.8 mmol/L at Randomization
  3. Serum sodium <135 mmol/L at Screening
  4. History of heart failure, myocardial infarction, stroke, or transient ischemic attack within 6 months prior to Screening.
  5. Diabetes mellitus with a glycosylated hemoglobin (HbA1c) >9% (>74.9 mmol/mol) at Screening

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Dose 2lorundrostat Dose 2lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks
Dose 1lorundrostat Dose 1lorundrostat Dose 1 once daily for 12 weeks
PlaceboPlaceboPlacebo once daily for 12 weeks
Primary Outcome Measures
NameTimeMethod
Change in 24-hour average ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP)Baseline (Randomization) to Week 12
Secondary Outcome Measures
NameTimeMethod
Change from baseline in 24-hour average ABPM SBP at Week 4 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placeboBaseline to Week 4
Proportion of subjects with 24-hour average ABPM SBP <125 mmHg at Week 4 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placeboat Week 4
Change from baseline in 24-hour average ABPM SBP at Week 4 by obesity status in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placeboBaseline to Week 4
Change from baseline in automated office BP (AOBP) SBP at Week 12 in subjects who were escalated to lorundrostat 100 mg QD at Week 4 (within-subjects analysis)Baseline to Week 12
Change from baseline in 24-hour average ABPM SBP at Week 4, by number of AHT medications in the standardized AHT regimen (2 and 3) in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placeboBaseline to Week 4
Proportion of subjects with 24-hour average ABPM SBP <125 mmHg at Week 12 in subjects randomized to lorundrostat (by arm and pooled dosages) compared to subjects randomized to placeboBaseline to Week 12
Change from baseline in 24-hour average ABPM SBP at Week 12 by obesity status in subjects randomized to lorundrostat (by arm and pooled dosages) compared to subjects randomized to placeboBaseline to Week 12
Change from baseline in daytime average ABPM SBP at Week 4 and Week 12 in subjects randomized to lorundrostat 50 mg (Week 4) and by arm and pooled dosages (Week 12) compared to subjects randomized to placeboBaseline to Week 4 and Week 12
Change from baseline in AOBP SBP at Week 4 and Week 12 in subjects randomized to lorundrostat 50 mg QD (Week 4) and by arm and pooled dosages (Week 12) compared to subjects randomized to placeboBaseline to Week 4 and Week 12
Change from baseline in nighttime average ABPM SBP at Week 4 and Week 12 in subjects randomized to lorundrostat 50 mg QD (Week 4) and by arm and pooled dosages (Week 12) compared to subjects randomized to placeboBaseline to Week 4 and Week 12
Change from baseline in 24-hour average ABPM SBP at Week 12, in subjects randomized to lorundrostat (pooled dosages) compared to subjects randomized to placeboBaseline to Week 12

Trial Locations

Locations (103)

Cardiology, P.C. - Birmingham

🇺🇸

Birmingham, Alabama, United States

University of Alabama at Birmingham (UAB) - Vascular Biology and Hypertension Program

🇺🇸

Birmingham, Alabama, United States

Chandler Clinical Trials

🇺🇸

Chandler, Arizona, United States

Brown Road Family Medicine

🇺🇸

Mesa, Arizona, United States

Scottsdale Clinical Trials (Elite Clinical Network)

🇺🇸

Scottsdale, Arizona, United States

Fiel Family & Sports Medicine

🇺🇸

Tempe, Arizona, United States

Noble Clinical Research

🇺🇸

Tucson, Arizona, United States

Del Sol Research Management, LLC

🇺🇸

Tuscon, Arizona, United States

The Medical Research Group Inc.

🇺🇸

Fresno, California, United States

Marvel Clinical Research

🇺🇸

Huntington Beach, California, United States

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Cardiology, P.C. - Birmingham
🇺🇸Birmingham, Alabama, United States
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