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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: lorundrostat Dose 1; Drug: lorundrostat Dose 2

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 Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology, P.C. - Birmingham
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham (UAB) - Vascular Biology and Hypertension Program
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Chandler Clinical Trials
    • Mesa, Arizona, United States, 85213
      • Brown Road Family Medicine
    • Scottsdale, Arizona, United States, 85260
      • Scottsdale Clinical Trials (Elite Clinical Network)
    • Tempe, Arizona, United States, 85383
      • Fiel Family & Sports Medicine
    • Tucson, Arizona, United States, 85704
      • Noble Clinical Research
    • Tucson, Arizona, United States, 85715
      • Del Sol Research Management, LLC
  • California
    • Fresno, California, United States, 93720
      • The Medical Research Group Inc.
    • Huntington Beach, California, United States, 92647
      • Marvel Clinical Research
    • La Jolla, California, United States, 92037
      • University of California San Diego (UCSD) - Altman Clinical and Translational Research Institute (ACTRI)
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Montclair, California, United States, 91763
      • Catalina Research Institute
    • Northridge, California, United States, 91325
      • Northridge Clinical Trials
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • San Diego, California, United States, 92108
      • TriWest Research Associates
    • San Jose, California, United States, 95117
      • San Jose Clinical Trials
    • Vista, California, United States, 92081
      • Blue Coast Research Center
    • Vista, California, United States, 92083
      • Accelerated Enrollment Solutions (AES)- Vista
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves, Inc.
  • Connecticut
    • Hamden, Connecticut, United States, 06517
      • CMR of Greater New Haven
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc.
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc (Jacksonville)
    • Miami, Florida, United States, 33186
      • Nuovida Research Center Corp
    • Miami, Florida, United States, 33176
      • Reserka, LLC
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
    • Pembroke, Florida, United States, 33026
      • Patron Medical - Andres Patron D.O. (Patron Ventures, LLC)
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Tampa, Florida, United States, 33606
      • Clinical Research of West Florida, Inc.
    • Vero Beach, Florida, United States, 32960
      • The Pierone Research Institute (Elligo Health Research)
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Nephrology Associates, PC - Downtown Augusta
    • Decatur, Georgia, United States, 30030
      • Accel Research Sites
    • Lawrenceville, Georgia, United States, 30044
      • Georgia Clinical Research, LLC
    • Peachtree City, Georgia, United States, 30269
      • Randomize Now
    • Peachtree Corners, Georgia, United States, 30092
      • Alta Pharmaceutical Research Center
    • Savannah, Georgia, United States, 31406
      • Fellows Research Alliance, Inc
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medicine
    • Chicago, Illinois, United States, 60621
      • Eagle Clinical Research
    • Evergreen Park, Illinois, United States, 60805
      • GenHarp Clinical Solutions
    • Springfield, Illinois, United States, 62702
      • Southern Illinois School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Physician Network-Indiana Heart Physicians
    • Merrillville, Indiana, United States, 46410
      • Indiana Clinical Research
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • The Research Group of Lexington, LLC
    • Paducah, Kentucky, United States, 42001
      • Advanced Internal Medicine, PLLC (Elligo Health Research)
    • Versailles, Kentucky, United States, 40383
      • Versailles Family Medicine
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Cambridge Clinical Trials
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, LLC
  • Missouri
    • St Louis, Missouri, United States, 63104
      • Saint Louis University
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research Inc. (QCR) - Omaha
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Henderson Clinical Trials
    • Las Vegas, Nevada, United States, 89030
      • Las Vegas Clinical Trials
    • Las Vegas, Nevada, United States, 89121
      • Oasis Clinical Trials
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • Seacoast Kidney & Hypertension Specialist
  • New York
    • Albany, New York, United States, 12203
      • Albany Medical College Div of Community Endocrinology
    • Buffalo, New York, United States, 14215
      • University of Buffalo
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 11415
      • Marian David, MD, PC (Elligo Health Research)
  • North Carolina
    • Asheboro, North Carolina, United States, 27205
      • Triad Internal Medicine
    • Asheville, North Carolina, United States, 28803
      • Asheville Clinical Trials (Elite Clinical Network)
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Heart Center Clinical Research Unit
    • Greenville, North Carolina, United States, 27834
      • East Carolina University (ECU) Physicians - East Carolina Heart Institute - East Carolina University Location
    • New Bern, North Carolina, United States, 28557
      • Lucas Research, Inc.
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital, Inc (Elligo Health Research)
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research LLC
  • Ohio
    • Beavercreek, Ohio, United States, 45431
      • Research Innovations (Elligo Health Research)
    • Canton, Ohio, United States, 44718
      • Diabetes and Endocrinology Associates of Stark County, Inc.
    • Cincinnati, Ohio, United States, 45245
      • Intrepid Research
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Dublin, Ohio, United States, 43016
      • Centricity Research (Aventiv Research) - Women's Health
    • Springboro, Ohio, United States, 45066
      • STAT Research
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Williamette Valley Clincial Studies
  • Pennsylvania
    • Horsham, Pennsylvania, United States, 19044
      • AMS Cardiology
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Accelerated Enrollment Solutions (AES)- Anderson
    • Charleston, South Carolina, United States, 29414
      • WR- Notus Clinical Trials, LLC
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Medical Research
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc
    • Memphis, Tennessee, United States, 38115
      • Lifedoc Research
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center (VUMC)
  • Texas
    • Austin, Texas, United States, 78704
      • Elligo Health Research
    • Carrollton, Texas, United States, 75006
      • Punzi Medical Center
    • El Paso, Texas, United States, 79905
      • David Turbay, MD, PLLC (Elligo Health Research)
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute
    • Houston, Texas, United States, 77040
      • Juno Research LLC
    • Houston, Texas, United States, 77070
      • Gulf Coast Clinical Research
    • Katy, Texas, United States, 77450
      • Medical Colleagues of Texas, LLP (Elligo Health Research)
    • Katy, Texas, United States, 77494
      • Synergy Groups Medical - Bissonet Site
    • Mesquite, Texas, United States, 75149
      • PRX Research - Mesquite
    • Paris, Texas, United States, 75462
      • Medical Colleagues of Texas, LLP (Elligo Health Research)
    • Plano, Texas, United States, 75024
      • ACRC Trials
    • Plano, Texas, United States, 75075
      • Clinical Investigations of Texas (CIT)
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute (SRI) - San Antonio
    • San Antonio, Texas, United States, 78240
      • San Antonio Clinical Trials
    • Sugar Land, Texas, United States, 77479
      • Sugar Lakes Family Practice (Elligo Health Research)
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • The University of Utah
  • Virginia
    • Burke, Virginia, United States, 22015
      • Burke Internal Medicine
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Norfolk, Virginia, United States, 23510
      • Eastern Virginia Medical School
    • Suffolk, Virginia, United States, 23435
      • Centricity Research (IACT Health) (Hampton Roads Center For Clinical Research, Inc.)) - Suffolk Multispecialty Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo once daily for 12 weeks	Drug: Placebo; Placebo once daily for 12 weeks
Experimental: Dose 1; lorundrostat Dose 1 once daily for 12 weeks	Drug: lorundrostat Dose 1; lorundrostat Dose 1 once daily for 12 weeks
Experimental: Dose 2; lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks	Drug: lorundrostat Dose 2; lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks for subjects who meet prespecified criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	Time Frame
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

Collaborators and Investigators

• Sponsor: Mineralys Therapeutics Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Actual): January 15, 2025
• Study Completion (Actual): January 15, 2025

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Actual): March 15, 2023

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Hypertension; Hypertensive; Blood pressure; Uncontrolled hypertension; Resistant hypertension
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension
• Other Study ID Numbers: MLS-101-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No