Clinical trial NCT05769608: A Pivotal Study to Evaluate the Efficacy of Lorundrostat in Subjects With Uncontrolled Hypertension on a Standardized Antihypertensive Medication Regimen
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: Blood pressure
Uncontrolled hypertension
Hypertension
Hypertensive
Resistant hypertension
Lead sponsor: Mineralys Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-15
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in 24-hour average ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP)
timeFrame: Baseline (Randomization) to Week 12
Secondary outcomes:
measure: 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
timeFrame: Baseline to Week 4
measure: 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
timeFrame: at Week 4
measure: 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
timeFrame: Baseline to Week 4
measure: 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)
timeFrame: Baseline to Week 12
measure: 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
timeFrame: Baseline to Week 4
measure: 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
timeFrame: Baseline to Week 12
measure: 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
timeFrame: Baseline to Week 12
measure: 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
timeFrame: Baseline to Week 4 and Week 12
measure: 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
timeFrame: Baseline to Week 4 and Week 12
measure: 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
timeFrame: Baseline to Week 4 and Week 12
measure: 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
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology, P.C. - Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB) - Vascular Biology and Hypertension Program
state: Alabama
city: Chandler
country: United States
facility: Chandler Clinical Trials
state: Arizona
city: Mesa
country: United States
facility: Brown Road Family Medicine
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale Clinical Trials (Elite Clinical Network)
state: Arizona
city: Tempe
country: United States
facility: Fiel Family & Sports Medicine
state: Arizona
city: Tucson
country: United States
facility: Noble Clinical Research
state: Arizona
city: Tuscon
country: United States
facility: Del Sol Research Management, LLC
state: Arizona
city: Fresno
country: United States
facility: The Medical Research Group Inc.
state: California
city: Huntington Beach
country: United States
facility: Marvel Clinical Research
state: California
city: La Jolla
country: United States
facility: University of California San Diego (UCSD) - Altman Clinical and Translational Research Institute (ACTRI)
state: California
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
city: Northridge
country: United States
facility: Northridge Clinical Trials
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: San Diego
country: United States
facility: Triwest Research Associates
state: California
city: San Jose
country: United States
facility: San Jose Clinical Trials
state: California
city: Vista
country: United States
facility: Blue Coast Research Center
state: California
city: Vista
country: United States
facility: Accelerated Enrollment Solutions (AES)- Vista
state: California
city: Colorado Springs
country: United States
facility: Delta Waves, Inc.
state: Colorado
city: Hamden
country: United States
facility: CMR of Greater New Haven
state: Connecticut
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc.
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc (Jacksonville)
state: Florida
city: Miami
country: United States
facility: Reserka, LLC
state: Florida
city: Miami
country: United States
facility: Nuovida Research Center Corp
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, INC.
state: Florida
city: Pembroke
country: United States
facility: Patron Medical - Andres Patron D.O. (Patron Ventures, LLC)
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Vero Beach
country: United States
facility: The Pierone Research Institute (Elligo Health Research)
state: Florida
city: Augusta
country: United States
facility: Nephrology Associates, PC - Downtown Augusta
state: Georgia
city: Decatur
country: United States
facility: Accel Research Sites
state: Georgia
city: Lawrenceville
country: United States
facility: Georgia Clinical Research, LLC
state: Georgia
city: Peachtree City
country: United States
facility: Randomize Now
state: Georgia
city: Peachtree Corners
country: United States
facility: Alta Pharmaceutical Research Center
state: Georgia
city: Savannah
country: United States
facility: Fellows Research Alliance, Inc
state: Georgia
city: Chicago
country: United States
facility: Eagle Clinical Research
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
city: Evergreen Park
country: United States
facility: GenHarp Clinical Solutions
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan Physician Network-Indiana Heart Physicians
state: Indiana
city: Merrillville
country: United States
facility: Indiana Clinical Research
state: Indiana
city: Lexington
country: United States
facility: The Research Group of Lexington, LLC
state: Kentucky
city: Paducah
country: United States
facility: Advanced Internal Medicine, PLLC (Elligo Health Research)
state: Kentucky
city: Versailles
country: United States
facility: Versailles Family Medicine
state: Kentucky
city: Alexandria
country: United States
facility: Cambridge Clinical Trials
state: Louisiana
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
city: Boston
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: Methuen
country: United States
facility: ActivMed Practices & Research, LLC
state: Massachusetts
city: St. Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Omaha
country: United States
facility: Quality Clinical Research Inc. (QCR) - Omaha
state: Nebraska
city: Henderson
country: United States
facility: Henderson Clinical Trials
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Clinical Trials
state: Nevada
city: Las Vegas
country: United States
facility: Oasis Clinical Trials
state: Nevada
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Portsmouth
country: United States
facility: Seacoast Kidney & Hypertension Specialist
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical College Div of Community Endocrinology
state: New York
city: Buffalo
country: United States
facility: University of Buffalo
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Marian David, MD, PC (Elligo Health Research)
state: New York
city: Asheboro
country: United States
facility: Triad Internal Medicine
state: North Carolina
city: Ashville
country: United States
facility: Asheville Clinical Trials (Elite Clinical Network)
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center Heart Center Clinical Research Unit
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University (ECU) Physicians - East Carolina Heart Institute - East Carolina University Location
state: North Carolina
city: New Bern
country: United States
facility: Lucas Research, Inc.
state: North Carolina
city: Statesville
country: United States
facility: Iredell Memorial Hospital, Inc (Elligo Health Research)
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research LLC
state: North Dakota
city: Beavercreek
country: United States
facility: Research Innovations (Elligo Health Research)
state: Ohio
city: Canton
country: United States
facility: Diabetes and Endocrinology Associates of Stark County, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Intrepid Research
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dublin
country: United States
facility: Centricity Research (Aventiv Research) - Women's Health
state: Ohio
city: Springboro
country: United States
facility: STAT Research
state: Ohio
city: Eugene
country: United States
facility: Williamette Valley Clincial Studies
state: Oregon
city: Horsham
country: United States
facility: AMS Cardiology
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Anderson
country: United States
facility: Accelerated Enrollment Solutions (AES)- Anderson
state: South Carolina
city: Charleston
country: United States
facility: WR- Notus Clinical Trials, LLC
state: South Carolina
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Medical Research
state: Tennessee
city: Memphis
country: United States
facility: Lifedoc Research
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (VUMC)
state: Tennessee
city: Austin
country: United States
facility: Elligo Health Research
state: Texas
city: Carrollton
country: United States
facility: Punzi Medical Center
state: Texas
city: El Paso
country: United States
facility: David Turbay, MD, PLLC (Elligo Health Research)
state: Texas
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: Houston
country: United States
facility: Juno Research LLC
state: Texas
city: Houston
country: United States
facility: Gulf Coast Clinical Research
state: Texas
city: Katy
country: United States
facility: Medical Colleagues of Texas, LLP (Elligo Health Research)
state: Texas
city: Katy
country: United States
facility: Synergy Groups Medical - Bissonet Site
state: Texas
city: Mesquite
country: United States
facility: PRX Research - Mesquite
state: Texas
city: Paris
country: United States
facility: Medical Colleagues of Texas, LLP (Elligo Health Research)
state: Texas
city: Plano
country: United States
facility: ACRC Trials
state: Texas
city: Plano
country: United States
facility: Clinical Investigations of Texas (CIT)
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute (SRI) - San Antonio
state: Texas
city: San Antonio
country: United States
facility: San Antonio Clinical Trials
state: Texas
city: Sugar Land
country: United States
facility: Sugar Lakes Family Practice (Elligo Health Research)
state: Texas
city: Salt Lake City
country: United States
facility: The University of Utah
state: Utah
city: Burke
country: United States
facility: Burke Internal Medicine
state: Virginia
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Suffolk
country: United States
facility: Centricity Research (IACT Health) (Hampton Roads Center For Clinical Research, Inc.)) - Suffolk Multispecialty Research
state: Virginia
Study officials:
References: