Clinical trial NCT06153693: Efficacy and Safety of Lorundrostat in Subjects With Uncontrolled and Resistant Hypertension
Official title: A Randomized, Double-Blind, Placebo Controlled, Parallel Arm, Multicenter Phase 3 Study to Evaluate the Efficacy and Safety of Lorundrostat in Subjects With Uncontrolled and Resistant Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Blood pressure
Hypertension
Hypertensive
Resistant hypertension
Uncontrolled hypertension
Lead sponsor: Mineralys Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-01
Enrollment: 1083
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: This is a Phase 3 trial to evaluate the BP-lowering effect of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled and resistant hypertension taking between 2 and 5 anti-hypertensive (AHT) medications.

Detailed description: This study is a Phase 3 trial to evaluate the BP-lowering effect of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled and resistant hypertension taking between 2 and 5 anti-hypertensive (AHT) medications, one of which must be a thiazide or thiazide-like diuretic.

The study consists of a 2-week screening period with a 2-week single-blind run-in period followed by a 12-week randomized, double-blind, placebo-controlled, parallel arm period. Following the randomized period subjects will be offered an opportunity to participate in an open-label extension (OLE) study. Any subject electing to not participate in the OLE will undergo an end of study (EoS) visit, which will occur after end of treatment (EoT), 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 (ICF)
2. At Screening and Randomization: AOBP SBP of ≥135 and ≤180 mmHg plus AOBP DBP of ≥65 and ≤110 mmHg, or AOBP DBP of ≥90 and ≤110 mmHg
3. Taking between 2 and 5 AHT medications,
4. History of hypertension lasting at least 6 months prior to Screening
5. Body mass index (BMI) of ≥18 kg/m2 at Screening

Exclusion Criteria:

1. Women who are pregnant, plan to become pregnant, or are breastfeeding
2. Participation in a study involving any investigational device or small-molecule drug within 4 weeks or 6 months for biologic (antibody) drugs prior to the Screening Visit
3. eGFR \<45 mL/min/1.73m2 at Screening, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
4. Serum potassium \>5.0 mmol/L at Screening or \>4.8 mmol/L at Randomization
5. Serum sodium \<135 mmol/L (corrected for hyperglycemia) at Screening.
6. History of heart failure, myocardial infarction, stroke, or transient ischemic attack within 6 months prior to the Screening Visit.

Primary outcomes:
measure: Change from baseline in automated office BP (AOBP) SBP at Week 6 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo
timeFrame: Week 6
Secondary outcomes:
measure: Proportion of subjects with AOBP SBP <130 mmHg at Week 6 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo
timeFrame: Week 6
measure: Change from baseline in AOBP SBP at Week 12 in subjects randomized to lorundrostat 50 mg QD with escalation to lorundrostat 100 mg QD compared to subjects randomized to placebo
timeFrame: Week 12
measure: Change from baseline in AOBP SBP at Week 6 in subjects with uncontrolled hypertension on 2 prescribed AHT medications
timeFrame: Week 6
measure: Change from baseline in AOBP SBP at Week 6 in subjects with uncontrolled hypertension on 3 or more prescribed AHT medications
timeFrame: Week 6
measure: Change from baseline in AOBP SBP at Week 6 by obesity status in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo
timeFrame: Week 6
measure: Change from baseline in AOBP SBP at Week 12 in subjects who were escalated to lorundrostat 100 mg QD at week 6 (within-subjects analysis)
timeFrame: Week 12
Other outcomes:
Locations:
city: Alexander City
country: United States
facility: Advanced Cardiovascular, LLC - Alexander City Office
state: Alabama
city: Birmingham
country: United States
facility: Central Research Associates, Inc
state: Alabama
city: Birmingham
country: United States
facility: Cardiology, P.C.
state: Alabama
city: Birmingham
country: United States
facility: Synexus (Radiant Research, Inc) - Alabama - Simon Williamson Clinic Location
state: Alabama
city: Foley
country: United States
facility: G & L Research LLC - Foley
state: Alabama
city: Vestavia Hills
country: United States
facility: Accel Research Sites (ARS) - Birmingham Clinical Research Unit
state: Alabama
city: Tucson
country: United States
facility: Del Sol Research
state: Arizona
city: Beverly Hills
country: United States
facility: Entertainment Medical Group, Inc.
state: California
city: Granada Hills
country: United States
facility: Amicis Research Center - Granada Hills
state: California
city: Granada Hills
country: United States
facility: Amicis Research Center - Northridge
state: California
city: Huntington Beach
country: United States
facility: Marvel Clinical Research, LLC
state: California
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Pasadena
country: United States
facility: Pasadena Clinical Trials
state: California
city: Pomona
country: United States
facility: Empire Clinical Research (ECR)
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research (CTR) - Sacramento
state: California
city: San Dimas
country: United States
facility: North America Research Institute
state: California
city: Valencia
country: United States
facility: Amicis Research Center - Valencia
state: California
city: Hamden
country: United States
facility: CMR of Greater New Haven
state: Connecticut
city: Waterbury
country: United States
facility: Chase Medical Research, LLC - Hamden
state: Connecticut
city: Hialeah
country: United States
facility: Indago Research and Health Center
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions (CNS Healthcare) - Jacksonville
state: Florida
city: Miami
country: United States
facility: Nuovida Research Center Corp
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions (CNS Healthcare) - Orlando Research Center
state: Florida
city: Orlando
country: United States
facility: AES Orlando
state: Florida
city: Pembroke Pines
country: United States
facility: Patron Medical - Andres Patron D.O. (Patron Ventures, LLC)
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Care Research Center, 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 (CRWF) - Clearwater
state: Florida
city: The Villages
country: United States
facility: AES The Villages
state: Florida
city: Atlanta
country: United States
facility: Morehouse School of Medicine (MSM)
state: Georgia
city: Columbus
country: United States
facility: ClinCept, LLC
state: Georgia
city: Decatur
country: United States
facility: Accel Research Sites- Decatur
state: Georgia
city: Lawrenceville
country: United States
facility: Georgia Clinical Research Center, Inc
state: Georgia
city: Blackfoot
country: United States
facility: Elite Clinical Trials
state: Idaho
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes Center
state: Idaho
city: Meridian
country: United States
facility: Solaris Clinical Research (SCR)
state: Idaho
city: Chicago
country: United States
facility: Synexus (Radiant Research, Inc) - Chicago
state: Illinois
city: Flossmoor
country: United States
facility: Healthcare Research Network-Chicago, Illinois (Flossmoor) Location
state: Illinois
city: Morton
country: United States
facility: Koch Family Medicine, S.C.
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine - SIU Clinics - SIU Internal Medicine
state: Illinois
city: Brownsburg
country: United States
facility: Investigators Research Group LLC
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan Physician Network
state: Indiana
city: Munster
country: United States
facility: ASHA Clinical Research- Munster, LLC
state: Indiana
city: Newburgh
country: United States
facility: Synexus (Radiant Research, Inc) - Evansville
state: Indiana
city: Louisville
country: United States
facility: Louisville Metabolic and Atherosclerosis Research Center (L-MARC)
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Doctors - Heart & Vascular - Metairie
state: Louisiana
city: New Orleans
country: United States
facility: The Alliance for Multispecialty Research LLC (AMR) - Louisiana
state: Louisiana
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology, LLC - Shreveport
state: Louisiana
city: Shreveport
country: United States
facility: Grace Research, LLC
state: Louisiana
city: Boston
country: United States
facility: Boston Clinical Trials (BCT)
state: Massachusetts
city: Methuen
country: United States
facility: ActivMed Practices and Research
state: Massachusetts
city: Petal
country: United States
facility: Hattiesburg Clinic - Medisync Clinical Research
state: Mississippi
city: Hazelwood
country: United States
facility: Healthcare Research Network-Hazelwood
state: Missouri
city: Kansas City
country: United States
facility: Clinical Research Consultants (CRC) - Kansas City
state: Missouri
city: Omaha
country: United States
facility: Quality Clinical Research Inc. (QCR) - Omaha
state: Nebraska
city: Henderson
country: United States
facility: Synexus (Radiant Research, Inc) - Nevada - Rita B. Chuang, MD
state: Nevada
city: Las Vegas
country: United States
facility: Sierra Clinical Research-Las Vegas
state: Nevada
city: Reno
country: United States
facility: Renown Regional Medical Center (Washoe Medical Center)
state: Nevada
city: Jamaica
country: United States
facility: Synexus (Radiant Research, Inc) - New York
state: New York
city: New Hyde Park
country: United States
facility: North Shore Diabetes and Endocrine Associates (NSDEA) - New Hyde Park
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Asheboro
country: United States
facility: Randolph Health Internal Medicine/ Triad Internal Medicine
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: Greenville
country: United States
facility: Physicians East, P.A. - Endocrinology
state: North Carolina
city: Morehead City
country: United States
facility: Carteret Medical Group - Morehead City
state: North Carolina
city: New Bern
country: United States
facility: Lucas Research, Inc. (Diabetes & Endocrinology Consultants PC) (DEC)
state: North Carolina
city: Canton
country: United States
facility: Diabetes & Endocrinology Associates of Stark County
state: Ohio
city: Norman
country: United States
facility: Lynn Institute of Norman (LION Research)
state: Oklahoma
city: Bethlehem
country: United States
facility: Valley Kidney Specialists PC - Allentown Cedar Crest
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians - Pleasant Hills - Curry Hollow Rd Location
state: Pennsylvania
city: Uniontown
country: United States
facility: Preferred Primary Care Physicians (PPCP) - Uniontown - Jacob Murphy Lane Location
state: Pennsylvania
city: Chattanooga
country: United States
facility: Chattanooga Medical Research (CMR), LLC
state: Tennessee
city: Knoxville
country: United States
facility: The Alliance for Multispecialty Research LLC (AMR) - Knoxville (Volunteer Research Group)
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Tennessee
city: Carrollton
country: United States
facility: Punzi Medical Center and Trinity Hypertension Research Institute
state: Texas
city: Dallas
country: United States
facility: AES Dallas Fort Worth
state: Texas
city: Houston
country: United States
facility: Synergy Groups Medical
state: Texas
city: Houston
country: United States
facility: Juno Research, LLC
state: Texas
city: McAllen
country: United States
facility: Discovery Clinical Trials (DCT) - McAllen
state: Texas
city: Missouri City
country: United States
facility: Synergy Groups Medical - Missouri City
state: Texas
city: Plano
country: United States
facility: North Texas Family Medicine (NTFM) - Plano Office
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute (SRI) - San Antonio
state: Texas
city: San Antonio
country: United States
facility: Discovery Clinical Trials (DCT) - San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Global AES - Salt Lake City
state: Utah
city: West Jordan
country: United States
facility: Velocity Clinical Research - Salt Lake City (Advanced Clinical Research)
state: Utah
city: Burke
country: United States
facility: Burke Internal Medicine
state: Virginia
city: Norfolk
country: United States
facility: Eastern VA Medical School
state: Virginia
city: Castle Hill
country: Australia
facility: Castle Hill Medical Centre
state: New South Wales
city: Gosford
country: Australia
facility: Renal Research - Gosford
state: New South Wales
city: Waratah
country: Australia
facility: University of Newcastle - John Hunter Hospital (JHH)
state: New South Wales
city: Sippy Downs
country: Australia
facility: University of the Sunshine Coast - Clinical Trials Centre
state: Queensland
city: Southport
country: Australia
facility: South Coast Renal
state: Queensland
city: Taringa
country: Australia
facility: AusTrials - Taringa
state: Queensland
city: Taringa
country: Australia
facility: AusTrials - Wellers Hill
state: Queensland
city: Adelaide
country: Australia
facility: Fusion Clinical Research
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Perth
country: Australia
facility: Dobney Hypertension Centre/ Royal Perth Hospital
state: Western Australia
city: Heidelberg Heights
country: Australia
facility: Austin Health - Heidelberg Repatriation Hospital
city: St Albans
country: Australia
facility: AusTrials - Sunshine
city: Gabrovo
country: Bulgaria
facility: Medical Center New Polyclinic Gabrovo Ltd.
city: Pleven
country: Bulgaria
facility: Medical center Exacta Medica
city: Sofia
country: Bulgaria
facility: Medical Center Hera EOOD - Sofia
city: Sofia
country: Bulgaria
facility: ASOMHIDC (Ambulatory of specialized outpatient medical help in internal diseases and cardiology)
city: Stara Zagora
country: Bulgaria
facility: Medical Centre Zara-Med
city: Veliko Tarnovo
country: Bulgaria
facility: DCC 1 - Veliko Tarnovo
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: East York
country: Canada
facility: Stephen S. Chow Medicine Professional Corporation
state: Ontario
city: Montreal
country: Canada
facility: Centre Medical L'Acadie - Montreal
state: Quebec
city: Annecy
country: France
facility: Centre Hospitalier Annecy Genevois (CHANGE) - Site d'Annecy -
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire (CHU) de Bordeaux - Hospitalier Saint-Andre
city: Nîmes
country: France
facility: Centre Hospitalier Universitaire de Nimes (CHU) - Hopital Universitaire Caremeau
city: Saint-Priest-en-Jarez
country: France
facility: Centre Hospitalier Universitaire (CHU) de Saint-Etienne - Hopital Nord
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg - Le Nouvel Hopital Civil (NHC)
city: Hannover
country: Germany
facility: kfgn Site Operations & Services GmbH (KFGN) - Klinische Forschung Hannover-Mitte GmbH (KFHM)
state: Lower Saxony
city: Mainz
country: Germany
facility: Pfuetzner Science & Health Institute GmbH (PSHI) - Diabeteszentrum & Praxis
state: Rhineland-Palatinate
city: Dresden
country: Germany
facility: kfgn Site Operations & Services GmbH (KFGN) - Klinische Forschung Dresden GmbH (KFDD)
state: Saxony
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig
state: Saxony
city: Berlin
country: Germany
facility: Charite-Universitaetsmedizin Berlin - Campus Benjamin Franklin (CBF)
city: Berlin
country: Germany
facility: emovis GmbH
city: Deggingen
country: Germany
facility: Gemeinscharftspraxis Dres Jung - Deggingen
city: Karlsruhe
country: Germany
facility: kfgn Site Operations & Services GmbH (KFGN) - Klinische Forschung Karlsruhe GmbH (KFKA)
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig - Klinik und Poliklinik fuer Pneumologie
city: Wiesbaden
country: Germany
facility: KfH Kuratorium fuer Dialyse und Nierentransplantation e.V. - KfH-Nierenzentrum Klaus-Ketzler-Zentrum
city: Rozzano
country: Italy
facility: Gruppo Humanitas - Humanitas Research Hospital (Istituto Clinico Humanitas)
state: Milan
city: Roma
country: Italy
facility: Azienda Ospedaliero-Universitaria Sant'Andrea Roma, Centro Ipertensione, UOC di Cardiologia
state: Rome
city: Ancona
country: Italy
facility: Istituto Nazionale di Riposo e Cura per Anziani (INRCA)
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
city: Brescia
country: Italy
facility: Universita degli Studi Di Brescia - Azienda Ospedaliera Spedali Civili di Brescia
city: Ferrara
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
city: L'Aquila
country: Italy
facility: Azienda Sanitaria Locale 1 (ASL 1) - Ospedale Regionale San Salvatore
city: Messina
country: Italy
facility: Universita degli Studi di Messina - Azienda Ospedaliera Universitaria Policlinico "Gaetano Martino" - Messina
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Modena
country: Italy
facility: AOU Policlinico di Modena - UO Cardiologia
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria (AOU) di Napoli
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo, - SC Ematologia, Dipartimento Oncoematologico
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Rome
country: Italy
facility: IRCCS San Raffaele
city: Nijmegen
country: Netherlands
facility: Radboud Universiteit - Radboud Universitair Medisch Centrum (Radboudumc)
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - Locatie AMC (Academisch Medisch Centrum)
state: North Holland
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis - Sliedrecht
state: South Holland
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum (UMC) Utrecht - Locatie AZU
city: Krakow
country: Poland
facility: Diamond Clinic Specjalistyczne Poradnie Lekarskie
state: Malopolskie
city: Lubin
country: Poland
facility: Velocity Lublin
state: Polska
city: Skierniewice
country: Poland
facility: Velocity Skierniewice Sp. z o.o
state: Polska
city: Warsaw
country: Poland
facility: ETG Network - Warszawa (European Trial Group)
state: Polska
city: Olsztyn
country: Poland
facility: Etyka OÅ>rodek BadaÅ" Klinicznych
state: Warminsko-Mazurskie
city: Katowice
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny im. Andrzeja Mieleckiego Slaskiego Uniwersytetu Medycznego w Katowicach
city: Katowice
country: Poland
facility: Silmedic Sp. z o.o
city: Olsztyn
country: Poland
facility: FutureMeds Sp. z o.o. Futuremeds Olsztyn
city: Łódź
country: Poland
facility: FutureMeds Sp. z o.o. FutureMeds Lodz
city: San Juan
country: Puerto Rico
facility: Latin Clinical Trial Center Inc. (LCTC)
city: Targu Mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Tg. Mures
state: Mures
city: Timişoara
country: Romania
facility: Centrul Medicali's Timisoara
state: Timis
city: Brasov
country: Romania
facility: Centrul Medical Unirea SRL Brasov (Regina Maria)
city: Bucharest
country: Romania
facility: Spitalul Clinic Colentina
city: Bucuresti
country: Romania
facility: Delta Health Care SRL Bucuresti - Spitalul Academic Ponderas (Regina Maria)
city: Cluj-Napoca
country: Romania
facility: Angiocare S.R.L. (Spitalul Ares Cluj-Napoca)
city: Craiova
country: Romania
facility: Spitalul Clinic Municipal Filantropia Craiova
city: Oradea
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Bihor
city: Timisoara
country: Romania
facility: S.C Materna Care SRL Timisoara (Regina Maria)
city: Timisoara
country: Romania
facility: Spitalul Clinic Judetean de Urgenta "Pius Branzeu" Timisoara
city: Badajoz
country: Spain
facility: Complejo Hospitalario Universitario de Badajoz (CHUB) (Hospital Infanta Cristina)
city: Barcelona
country: Spain
facility: Hospital del Mar - Institut Hospital del Mar d'Investigacions Mediques (IMIM)
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves (HUVN)
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Universidad Autonoma de Madrid (UAM) - Facultad de Medicina - Hospital Universitario Fundacion Jimenez Diaz (UAM-FJD) - Instituto de Investigacion Sanitaria (IIS)
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Hospital Clinico Universitario (University Clinical Hospital)
city: Valencia
country: Spain
facility: Instituto de Investigacion Sanitaria (INCLIVA)
city: Fowey
country: United Kingdom
facility: Fowey River Practice - Fowey Surgery
state: Great Britain
city: London
country: United Kingdom
facility: Queen Mary University of London (QMUL) - Barts and The London School of Medicine and Dentistry - William Harvey Research Institute (WHRI) - William Harvey Heart Centre (WHHC)
state: Great Britain
city: Plymouth
country: United Kingdom
facility: Knowle House Surgery
state: Great Britain
city: Torpoint
country: United Kingdom
facility: The Rame Group Practice (Dr. DAVIS & Partners) - Penntorr Health
state: Great Britain
city: Canterbury
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospital (AH)
state: Kent
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust - Birmingham Regional Severe Asthma Service (BRSAS)
city: Canterbury
country: United Kingdom
facility: East Kent Hospitals University NHS Foundation Trust
city: Carshalton
country: United Kingdom
facility: Epsom and St Helier University Hospitals NHS Trust
city: Chippenham
country: United Kingdom
facility: Rowden Surgery Rowden Medical Partnership
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde (NHSGGC)
city: Newquay
country: United Kingdom
facility: Newquay Health Centre
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust - Northern General Hospital
city: Stockton-on-Tees
country: United Kingdom
facility: FutureMeds - Stockton-on-Tees
Study officials:
References: