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.

Study Timeline

• Study First Submitted: 2023-02-24
• Study First Submitted QC: 2023-03-03
• Study Start: 2023-03-13
• Study First Posted: 2023-03-15
• Primary Completion: 2025-01-15
• Study Completion: 2025-01-15
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-14
• Last Update Posted: 2025-02-18

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

Group	Intervention	Description
Dose 2	lorundrostat Dose 2	lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks
Dose 1	lorundrostat Dose 1	lorundrostat Dose 1 once daily for 12 weeks
Placebo	Placebo	Placebo once daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Change in 24-hour average ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP)	Baseline (Randomization) to Week 12

Secondary Outcome Measures

Name	Time	Method
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 placebo	Baseline 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 placebo	at 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 placebo	Baseline 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 placebo	Baseline 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 placebo	Baseline 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 placebo	Baseline 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 placebo	Baseline 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 placebo	Baseline 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 placebo	Baseline 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 placebo	Baseline 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

University of California San Diego (UCSD) - Altman Clinical and Translational Research Institute (ACTRI); 🇺🇸 La Jolla, California, United States

Clinical Trials Research; 🇺🇸 Lincoln, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Catalina Research Institute; 🇺🇸 Montclair, California, United States

Northridge Clinical Trials; 🇺🇸 Northridge, California, United States

University of California Irvine Medical Center; 🇺🇸 Orange, California, United States

Triwest Research Associates; 🇺🇸 San Diego, California, United States

San Jose Clinical Trials; 🇺🇸 San Jose, California, United States

Blue Coast Research Center; 🇺🇸 Vista, California, United States

Accelerated Enrollment Solutions (AES)- Vista; 🇺🇸 Vista, California, United States

Delta Waves, Inc.; 🇺🇸 Colorado Springs, Colorado, United States

CMR of Greater New Haven; 🇺🇸 Hamden, Connecticut, United States

Indago Research & Health Center, Inc.; 🇺🇸 Hialeah, Florida, United States

Clinical Neuroscience Solutions, Inc (Jacksonville); 🇺🇸 Jacksonville, Florida, United States

Reserka, LLC; 🇺🇸 Miami, Florida, United States

Nuovida Research Center Corp; 🇺🇸 Miami, Florida, United States

Clinical Neuroscience Solutions, INC.; 🇺🇸 Orlando, Florida, United States

Patron Medical - Andres Patron D.O. (Patron Ventures, LLC); 🇺🇸 Pembroke, Florida, United States

Progressive Medical Research; 🇺🇸 Port Orange, Florida, United States

Clinical Research of West Florida, Inc.; 🇺🇸 Tampa, Florida, United States

The Pierone Research Institute (Elligo Health Research); 🇺🇸 Vero Beach, Florida, United States

Nephrology Associates, PC - Downtown Augusta; 🇺🇸 Augusta, Georgia, United States

Accel Research Sites; 🇺🇸 Decatur, Georgia, United States

Georgia Clinical Research, LLC; 🇺🇸 Lawrenceville, Georgia, United States

Randomize Now; 🇺🇸 Peachtree City, Georgia, United States

Alta Pharmaceutical Research Center; 🇺🇸 Peachtree Corners, Georgia, United States

Fellows Research Alliance, Inc; 🇺🇸 Savannah, Georgia, United States

Eagle Clinical Research; 🇺🇸 Chicago, Illinois, United States

The University of Chicago Medicine; 🇺🇸 Chicago, Illinois, United States

GenHarp Clinical Solutions; 🇺🇸 Evergreen Park, Illinois, United States

Southern Illinois School of Medicine; 🇺🇸 Springfield, Illinois, United States

Franciscan Physician Network-Indiana Heart Physicians; 🇺🇸 Indianapolis, Indiana, United States

Indiana Clinical Research; 🇺🇸 Merrillville, Indiana, United States

The Research Group of Lexington, LLC; 🇺🇸 Lexington, Kentucky, United States

Advanced Internal Medicine, PLLC (Elligo Health Research); 🇺🇸 Paducah, Kentucky, United States

Versailles Family Medicine; 🇺🇸 Versailles, Kentucky, United States

Cambridge Clinical Trials; 🇺🇸 Alexandria, Louisiana, United States

Pennington Biomedical Research Center; 🇺🇸 Baton Rouge, Louisiana, United States

Boston Clinical Trials; 🇺🇸 Boston, Massachusetts, United States

ActivMed Practices & Research, LLC; 🇺🇸 Methuen, Massachusetts, United States

Saint Louis University; 🇺🇸 St. Louis, Missouri, United States

Quality Clinical Research Inc. (QCR) - Omaha; 🇺🇸 Omaha, Nebraska, United States

Henderson Clinical Trials; 🇺🇸 Henderson, Nevada, United States

Las Vegas Clinical Trials; 🇺🇸 Las Vegas, Nevada, United States

Oasis Clinical Trials; 🇺🇸 Las Vegas, Nevada, United States

Renown Regional Medical Center; 🇺🇸 Reno, Nevada, United States

Seacoast Kidney & Hypertension Specialist; 🇺🇸 Portsmouth, New Hampshire, United States

Albany Medical College Div of Community Endocrinology; 🇺🇸 Albany, New York, United States

University of Buffalo; 🇺🇸 Buffalo, New York, United States

Columbia University; 🇺🇸 New York, New York, United States

Marian David, MD, PC (Elligo Health Research); 🇺🇸 New York, New York, United States

Triad Internal Medicine; 🇺🇸 Asheboro, North Carolina, United States

Asheville Clinical Trials (Elite Clinical Network); 🇺🇸 Ashville, North Carolina, United States

Duke University Medical Center Heart Center Clinical Research Unit; 🇺🇸 Durham, North Carolina, United States

East Carolina University (ECU) Physicians - East Carolina Heart Institute - East Carolina University Location; 🇺🇸 Greenville, North Carolina, United States

Lucas Research, Inc.; 🇺🇸 New Bern, North Carolina, United States

Iredell Memorial Hospital, Inc (Elligo Health Research); 🇺🇸 Statesville, North Carolina, United States

Lillestol Research LLC; 🇺🇸 Fargo, North Dakota, United States

Research Innovations (Elligo Health Research); 🇺🇸 Beavercreek, Ohio, United States

Diabetes and Endocrinology Associates of Stark County, Inc.; 🇺🇸 Canton, Ohio, United States

Intrepid Research; 🇺🇸 Cincinnati, Ohio, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Centricity Research (Aventiv Research) - Women's Health; 🇺🇸 Dublin, Ohio, United States

STAT Research; 🇺🇸 Springboro, Ohio, United States

Williamette Valley Clincial Studies; 🇺🇸 Eugene, Oregon, United States

AMS Cardiology; 🇺🇸 Horsham, Pennsylvania, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Accelerated Enrollment Solutions (AES)- Anderson; 🇺🇸 Anderson, South Carolina, United States

WR- Notus Clinical Trials, LLC; 🇺🇸 Charleston, South Carolina, United States

Coastal Carolina Research Center; 🇺🇸 North Charleston, South Carolina, United States

Chattanooga Medical Research; 🇺🇸 Chattanooga, Tennessee, United States

Lifedoc Research; 🇺🇸 Memphis, Tennessee, United States

Clinical Neuroscience Solutions, Inc; 🇺🇸 Memphis, Tennessee, United States

Vanderbilt University Medical Center (VUMC); 🇺🇸 Nashville, Tennessee, United States

Elligo Health Research; 🇺🇸 Austin, Texas, United States

Punzi Medical Center; 🇺🇸 Carrollton, Texas, United States

David Turbay, MD, PLLC (Elligo Health Research); 🇺🇸 El Paso, Texas, United States

Houston Methodist Research Institute; 🇺🇸 Houston, Texas, United States

Juno Research LLC; 🇺🇸 Houston, Texas, United States

Gulf Coast Clinical Research; 🇺🇸 Houston, Texas, United States

Medical Colleagues of Texas, LLP (Elligo Health Research); 🇺🇸 Paris, Texas, United States

Synergy Groups Medical - Bissonet Site; 🇺🇸 Katy, Texas, United States

PRX Research - Mesquite; 🇺🇸 Mesquite, Texas, United States

ACRC Trials; 🇺🇸 Plano, Texas, United States

Clinical Investigations of Texas (CIT); 🇺🇸 Plano, Texas, United States

Sun Research Institute (SRI) - San Antonio; 🇺🇸 San Antonio, Texas, United States

San Antonio Clinical Trials; 🇺🇸 San Antonio, Texas, United States

Sugar Lakes Family Practice (Elligo Health Research); 🇺🇸 Sugar Land, Texas, United States

The University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Burke Internal Medicine; 🇺🇸 Burke, Virginia, United States

Charlottesville Medical Research; 🇺🇸 Charlottesville, Virginia, United States

Eastern Virginia Medical School; 🇺🇸 Norfolk, Virginia, United States

Centricity Research (IACT Health) (Hampton Roads Center For Clinical Research, Inc.)) - Suffolk Multispecialty Research; 🇺🇸 Suffolk, Virginia, United States