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

NCT05769608 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: MLS-101-202
• Study Type: interventional
• Target: 285
• Locations: 1 country
• Sites: 104

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.

Conditions

Hypertension

Keywords

Blood pressure; Uncontrolled hypertension; Hypertension; Hypertensive; Resistant hypertension

Outcome Measures

Primary Outcomes (1)

• Change in 24-hour average ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP)

  Baseline (Randomization) to Week 12

Secondary Outcomes (11)

• 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

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo once daily for 12 weeks

Drug: Placebo

Dose 1

EXPERIMENTAL

lorundrostat Dose 1 once daily for 12 weeks

Drug: lorundrostat Dose 1

Dose 2

EXPERIMENTAL

lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks

Drug: lorundrostat Dose 2

Interventions

Placebo DRUG

Placebo once daily for 12 weeks

Placebo

lorundrostat Dose 1 DRUG

lorundrostat Dose 1 once daily for 12 weeks

Dose 1

lorundrostat Dose 2 DRUG

lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks for subjects who meet prespecified criteria

Dose 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mineralys Therapeutics Inc.: lead

Study Sites (104)

Cardiology, P.C. - Birmingham

Birmingham, Alabama, 35211, United States

Location

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

Birmingham, Alabama, 35294, United States

Location

Chandler Clinical Trials

Chandler, Arizona, 85224, United States

Location

Brown Road Family Medicine

Mesa, Arizona, 85213, United States

Location

Scottsdale Clinical Trials (Elite Clinical Network)

Scottsdale, Arizona, 85260, United States

Location

Fiel Family & Sports Medicine

Tempe, Arizona, 85383, United States

Location

Noble Clinical Research

Tucson, Arizona, 85704, United States

Location

Del Sol Research Management, LLC

Tucson, Arizona, 85715, United States

Location

The Medical Research Group Inc.

Fresno, California, 93720, United States

Location

Marvel Clinical Research

Huntington Beach, California, 92647, United States

Location

University of California San Diego (UCSD) - Altman Clinical and Translational Research Institute (ACTRI)

La Jolla, California, 92037, United States

Location

Clinical Trials Research

Lincoln, California, 95648, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Catalina Research Institute

Montclair, California, 91763, United States

Location

Northridge Clinical Trials

Northridge, California, 91325, United States

Location

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

Triwest Research Associates

San Diego, California, 92108, United States

Location

San Jose Clinical Trials

San Jose, California, 95117, United States

Location

Blue Coast Research Center

Vista, California, 92081, United States

Location

Accelerated Enrollment Solutions (AES)- Vista

Vista, California, 92083, United States

Location

Delta Waves, Inc.

Colorado Springs, Colorado, 80918, United States

Location

CMR of Greater New Haven

Hamden, Connecticut, 06517, United States

Location

Indago Research & Health Center, Inc.

Hialeah, Florida, 33012, United States

Location

Clinical Neuroscience Solutions, Inc (Jacksonville)

Jacksonville, Florida, 32256, United States

Location

Reserka, LLC

Miami, Florida, 33176, United States

Location

Nuovida Research Center Corp

Miami, Florida, 33186, United States

Location

Clinical Neuroscience Solutions, INC.

Orlando, Florida, 32801, United States

Location

Patron Medical - Andres Patron D.O. (Patron Ventures, LLC)

Pembroke, Florida, 33026, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Clinical Research of West Florida, Inc.

Tampa, Florida, 33606, United States

Location

The Pierone Research Institute (Elligo Health Research)

Vero Beach, Florida, 32960, United States

Location

Nephrology Associates, PC - Downtown Augusta

Augusta, Georgia, 30901, United States

Location

Accel Research Sites

Decatur, Georgia, 30030, United States

Location

Georgia Clinical Research, LLC

Lawrenceville, Georgia, 30044, United States

Location

Randomize Now

Peachtree City, Georgia, 30269, United States

Location

Alta Pharmaceutical Research Center

Peachtree Corners, Georgia, 30092, United States

Location

Fellows Research Alliance, Inc

Savannah, Georgia, 31406, United States

Location

Eagle Clinical Research

Chicago, Illinois, 60621, United States

Location

The University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

GenHarp Clinical Solutions

Evergreen Park, Illinois, 60805, United States

Location

Southern Illinois School of Medicine

Springfield, Illinois, 62702, United States

Location

Franciscan Physician Network-Indiana Heart Physicians

Indianapolis, Indiana, 46237, United States

Location

Indiana Clinical Research

Merrillville, Indiana, 46410, United States

Location

The Research Group of Lexington, LLC

Lexington, Kentucky, 40503, United States

Location

Advanced Internal Medicine, PLLC (Elligo Health Research)

Paducah, Kentucky, 42001, United States

Location

Versailles Family Medicine

Versailles, Kentucky, 40383, United States

Location

Cambridge Clinical Trials

Alexandria, Louisiana, 71301, United States

Location

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Boston Clinical Trials

Boston, Massachusetts, 02131, United States

Location

ActivMed Practices & Research, LLC

Methuen, Massachusetts, 01844, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Quality Clinical Research Inc. (QCR) - Omaha

Omaha, Nebraska, 68114, United States

Location

Henderson Clinical Trials

Henderson, Nevada, 89052, United States

Location

Las Vegas Clinical Trials

Las Vegas, Nevada, 89030, United States

Location

Oasis Clinical Trials

Las Vegas, Nevada, 89121, United States

Location

Renown Regional Medical Center

Reno, Nevada, 89502, United States

Location

Seacoast Kidney & Hypertension Specialist

Portsmouth, New Hampshire, 03801, United States

Location

Albany Medical College Div of Community Endocrinology

Albany, New York, 12203, United States

Location

University of Buffalo

Buffalo, New York, 14215, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Marian David, MD, PC (Elligo Health Research)

New York, New York, 11415, United States

Location

Triad Internal Medicine

Asheboro, North Carolina, 27205, United States

Location

Asheville Clinical Trials (Elite Clinical Network)

Asheville, North Carolina, 28803, United States

Location

Duke University Medical Center Heart Center Clinical Research Unit

Durham, North Carolina, 27710, United States

Location

East Carolina University (ECU) Physicians - East Carolina Heart Institute - East Carolina University Location

Greenville, North Carolina, 27834, United States

Location

Lucas Research, Inc.

New Bern, North Carolina, 28557, United States

Location

Iredell Memorial Hospital, Inc (Elligo Health Research)

Statesville, North Carolina, 28677, United States

Location

Lillestol Research LLC

Fargo, North Dakota, 58104, United States

Location

Research Innovations (Elligo Health Research)

Beavercreek, Ohio, 45431, United States

Location

Diabetes and Endocrinology Associates of Stark County, Inc.

Canton, Ohio, 44718, United States

Location

Intrepid Research

Cincinnati, Ohio, 45245, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Centricity Research (Aventiv Research) - Women's Health

Dublin, Ohio, 43016, United States

Location

STAT Research

Springboro, Ohio, 45066, United States

Location

Williamette Valley Clincial Studies

Eugene, Oregon, 97404, United States

Location

AMS Cardiology

Horsham, Pennsylvania, 19044, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Accelerated Enrollment Solutions (AES)- Anderson

Anderson, South Carolina, 29621, United States

Location

WR- Notus Clinical Trials, LLC

Charleston, South Carolina, 29414, United States

Location

Coastal Carolina Research Center

North Charleston, South Carolina, 29405, United States

Location

Chattanooga Medical Research

Chattanooga, Tennessee, 37404, United States

Location

Lifedoc Research

Memphis, Tennessee, 38115, United States

Location

Clinical Neuroscience Solutions, Inc

Memphis, Tennessee, 38119, United States

Location

Vanderbilt University Medical Center (VUMC)

Nashville, Tennessee, 37232, United States

Location

Elligo Health Research

Austin, Texas, 78704, United States

Location

Punzi Medical Center

Carrollton, Texas, 75006, United States

Location

David Turbay, MD, PLLC (Elligo Health Research)

El Paso, Texas, 79905, United States

Location

Houston Methodist Research Institute

Houston, Texas, 77030, United States

Location

Juno Research LLC

Houston, Texas, 77040, United States

Location

Gulf Coast Clinical Research

Houston, Texas, 77070, United States

Location

Medical Colleagues of Texas, LLP (Elligo Health Research)

Katy, Texas, 77450, United States

Location

Synergy Groups Medical - Bissonet Site

Katy, Texas, 77494, United States

Location

PRX Research - Mesquite

Mesquite, Texas, 75149, United States

Location

Medical Colleagues of Texas, LLP (Elligo Health Research)

Paris, Texas, 75462, United States

Location

ACRC Trials

Plano, Texas, 75024, United States

Location

Clinical Investigations of Texas (CIT)

Plano, Texas, 75075, United States

Location

Sun Research Institute (SRI) - San Antonio

San Antonio, Texas, 78215, United States

Location

San Antonio Clinical Trials

San Antonio, Texas, 78240, United States

Location

Sugar Lakes Family Practice (Elligo Health Research)

Sugar Land, Texas, 77479, United States

Location

The University of Utah

Salt Lake City, Utah, 84108, United States

Location

Burke Internal Medicine

Burke, Virginia, 22015, United States

Location

Charlottesville Medical Research

Charlottesville, Virginia, 22911, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23510, United States

Location

Centricity Research (IACT Health) (Hampton Roads Center For Clinical Research, Inc.)) - Suffolk Multispecialty Research

Suffolk, Virginia, 23435, United States

Location

Related Publications (1)

• Laffin LJ, Kopjar B, Melgaard C, Wolski K, Ibbitson J, Bhikam S, Weir MR, Ofili EO, Mehra R, Luther JM, Cohen DL, Sarraju A, Wilkinson MJ, Flack JM, Rodman D, Nissen SE; Advance-HTN Investigators. Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension. N Engl J Med. 2025 May 8;392(18):1813-1823. doi: 10.1056/NEJMoa2501440. Epub 2025 Apr 23.

  PMID: 40267417 DERIVED

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2023
• First Posted: March 15, 2023
• Study Start: March 13, 2023
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

US (104)