Efficacy and Safety of Lorundrostat in Addition to Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in Subjects With Hypertension and Chronic Kidney Disease (CKD) With Albuminuria

A Randomized, Crossover, Double Blind, Placebo Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Lorundrostat in Addition to Sodium-Glucose Cotransporter-2 Inhibitors, in Adults With Hypertension and Chronic Kidney Disease With Albuminuria

This is a randomized, double-blind (DB), placebo controlled, crossover study with a two-period, two-sequence (2x2) design evaluating the efficacy and safety of 25 mg QD lorundrostat (an aldosterone synthase inhibitor [ASI]) in addition to a SGLT2i for the treatment of hypertension in subjects with CKD and albuminuria while receiving stable treatment with an Angiotensin-converting enzyme inhibitor (ACEi) or an Angiotensin receptor blocker (ARB). Subjects will be at least 18 years old with hypertension, and mild to severe CKD with albuminuria at the Screening Visit.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Lorundrostat 25mg+SGLT2i QD, Washout, Placebo+SGLT2i QD; Drug: Placebo QD + SGLT2i QD, Washout, Lorundrostat 25mg+SGLT2i QD

Detailed Description

The study consists of up to a 2-week Screening period, a 2-week run-in period where subjects will either begin study provided dapagliflozin 10 mg or continue on their regularly prescribed SGLT2i, and two DB 4-week treatment periods separated by a 4-week washout period. Subjects will be randomized (1:1) to two treatment sequences: lorundrostat-placebo (LP) and placebo-lorundrostat (PL).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thunderbird Office
    • Phoenix, Arizona, United States, 85016
      • Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thomas Office
  • California
    • Chula Vista, California, United States, 91910
      • Balboa Nephrology Medical Group, Inc. (BNMG) - California Institute of Renal Research (CIRR) - Chula Vista
    • El Centro, California, United States, 92243
      • Balboa Nephrology Medical Group, Inc. (BNMG) - El Centro
    • Granada Hills, California, United States, 91344
      • Amicis Research Center - Granada Hills
    • La Mesa, California, United States, 91942-3059
      • Balboa Nephrology Medical Group, Inc. (Bnmg) - La Mesa
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute (AMRI) - Los Angeles
    • Northridge, California, United States, 91324
      • Amicis Research Center
    • Vacaville, California, United States, 95687-3560
      • Amicis Research Center - Vacaville
  • Colorado
    • Denver, Colorado, United States, 80218-1216
      • Colorado Kidney Care (Denver Nephrology) - Denver Office
  • Florida
    • Coconut Grove, Florida, United States, 33133
      • Qway Research
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center
    • Hollywood, Florida, United States, 33024
      • Elixia Pines, LLC
    • Orlando, Florida, United States, 32806
      • Elixia Central Florida, LLC
    • Sanford, Florida, United States, 32771
      • Infigo Clinical Research, Llc
    • Tampa, Florida, United States, 33614
      • Genesis Clinical Research - Tampa
    • West Palm Beach, Florida, United States, 33401
      • Palm Beach Diabetes and Endocrine Specialists, PA (PBDES) - West Palm Beach Office
  • Georgia
    • Acworth, Georgia, United States, 30101
      • American Clinical Trials Llc
    • Brunswick, Georgia, United States, 31520
      • Nephrology of the Golden Isles - Brunswick
    • Columbus, Georgia, United States, 32896
      • ClinCept, LLC
    • Lawrenceville, Georgia, United States, 30046-8761
      • Georgia Nephrology, Llc
  • Kentucky
    • Louisville, Kentucky, United States, 40205
      • Nephrology Associates of Kentuckiana, PSC (NAK)
  • Louisiana
    • New Orleans, Louisiana, United States, 70112-3018
      • Lcms Health University Medical Center New Orleans
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology, Llc - Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts University School of Medicine (Tusm) - Tufts Medical Center (Tmc) (Tufts-New England Medical Center)
  • Michigan
    • Pontiac, Michigan, United States, 48341
      • Elixia MKC, LLC
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Kansas City Kidney Consultants (Arms, Dodge, Robinson, Wilber & Crouch, Inc.) - Kansas City
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • Seacoast Kidney & Hypertension Specialists - Portsmouth Office
  • New York
    • Brooklyn, New York, United States, 11226-1508
      • Suny Downstate Medical Center - Parkside Dialysis Center
    • Fresh Meadows, New York, United States, 11365
      • Nephrology Associates
    • Fresh Meadows, New York, United States, 11365
      • Nephrology Associates, PC
  • North Carolina
    • Asheboro, North Carolina, United States, 27205
      • Triad Internal Medicine
    • Winston-Salem, North Carolina, United States, 27103
      • Nephrology Associates, Pllc - Winston-Salem
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116-1516
      • Nephrology Consultants - Oklahoma City
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Columbia Nephrology
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
      • Southeast Renal Research Institute
  • Texas
    • Dallas, Texas, United States, 75235
      • Dallas Nephrology Associates (Dna) - Renal Disease Research Institute (Rdri)
    • Dallas, Texas, United States, 75237
      • Liberty Research Center
    • Katy, Texas, United States, 27205
      • R&H Clinical Research
    • Lufkin, Texas, United States, 75904
      • E T Nephrology Associates - Lufkin
    • Mesquite, Texas, United States, 75149
      • Prx Research
    • Mission, Texas, United States, 78572
      • Gamma Medical Research, Inc
  • Utah
    • St. George, Utah, United States, 84790
      • Chrysalis Clinical Research (CCR)
  • Virginia
    • Woodbridge, Virginia, United States, 22191
      • Mendez Center for Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Major Inclusion Criteria:

1. At Screening, UACR of 200-5000 mg/g, inclusive, in first morning urine void
2. At Screening, eGFRs of ≥30 mL/min/1.73 m2
3. At Screening, AOBP SBP of 135-180 mmHg, inclusive
4. On a stable treatment with an ACEi or ARB for at least 2 months prior to Screening
5. At Screening, body mass index (BMI) of >18 kg/m2

Major Exclusion Criteria:

1. Subjects with known hypersensitivity to lorundrostat or any of its respective excipients
2. Subjects with known hypersensitivity to dapagliflozin or any of its respective excipients (subjects beginning dapagliflozin only)
3. At Screening, serum potassium >5.0 mmol/L
4. History of clinically significant hyponatremia within 1 year prior to Screening
5. Use of epithelial sodium channel (ENaC) inhibitors or Mineralocorticoid receptor antagonist (MRAs), including, but not limited to amiloride, triamterene, spironolactone, eplerenone, finerenone, from 4 weeks prior to the Screening Visit and during study participation. With the exception of MRAs in primary aldosteronism
6. Medical history of kidney disease related to autoimmune diseases (lupus, anti-neutrophil cytoplasmic antibody [ANCA] vasculitis), multiple myeloma or other known paraproteins, infiltrative diseases of the kidney, obstructive nephropathy, cystic kidney diseases, and renal transplantation
7. Medical history of advanced liver disease, including cirrhosis
8. Medical history of active autoimmune disease or recent (within 30 days) or anticipated need for immunosuppressive therapy
9. Diabetes mellitus with a glycosylated hemoglobin (HbA1c) >10% (>86 mmol/mol) at Screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	Drug: Lorundrostat 25mg+SGLT2i QD, Washout, Placebo+SGLT2i QD; Period 1 - Lorundrostat 25mg QD + SGLT2i QD 4 weeks; Washout - Placebo QD + SGLT2i QD 4 weeks; Period 2 - Placebo QD + SGLT2i QD 4 weeks
Experimental: Cohort 2	Drug: Placebo QD + SGLT2i QD, Washout, Lorundrostat 25mg+SGLT2i QD; Period 1 - Placebo QD + SGLT2i QD 4 weeks; Washout - Placebo QD + SGLT2i QD 4 weeks; Period 2 - Lorundrostat 25mg + SGLT2i QD 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Placebo-adjusted Change From Baseline in Automated Office Blood Pressure (AOBP) Systolic Blood Pressure (SBP) at Week 4	Baseline to Week 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A: Change from Week 12 in AOBP SBP at Week 20	Week 12 to Week 20
Part A: Percent change from baseline in 24-hour urine albumin to creatinine ratio (UACR) at Week 8	baseline to Week 8

Other Outcome Measures

Outcome Measure	Time Frame
Placebo-adjusted percent change from baseline in 24-hour urine albumin at Study Week 4	baseline to Study Week 4
Placebo-adjusted change from baseline in AOBP diastolic blood pressure (DBP) at Study Week 4	Study Week 4
Change from baseline in AOBP SBP at Study Week 4 lorundrostat treatment periods	Study Week 4
Percent change from baseline in 24-hour urine albumin at Study Week 4 in lorundrostat treatment periods	baseline to Study Week 4
Placebo-adjusted percent change from baseline in 24-hour urine protein Study Week 4	baseline to Study Week 4
Placebo-adjusted percent change from baseline in urine albumin to creatinine ratio (UACR) at Study Week 4	baseline to Study Week 4
Change in biomarkers from baseline to Study Week 4 in lorundrostat treatment periods	baseline to Study Week 4
Placebo-adjusted percent change in estimated glomerular filtration rate (eGFR) from baseline to Study Week 4	baseline to Study Week 4
Percent change in eGFR from Study Week 4 to Study Week 8	Study Week 4 to Study Week 8

Collaborators and Investigators

• Sponsor: Mineralys Therapeutics Inc.

Publications and helpful links

General Publications

• Hu S, Lee K, He JC, Fan Y. Current Landscape and Emerging Therapeutic Targets in Diabetic Kidney Disease. Clin J Am Soc Nephrol. 2026 Mar 10. doi: 10.2215/CJN.0000001053. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2023
• Primary Completion (Actual): February 27, 2025
• Study Completion (Actual): April 23, 2025

Study Registration Dates

• First Submitted: November 17, 2023
• First Submitted That Met QC Criteria: November 27, 2023
• First Posted (Actual): November 29, 2023

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hypertension; Chronic Kidney Disease; Proteinuria; Albuminuria; Arterial hypertension; Diabetic nephropathy; Aldosterone Synthase Inhibitor
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Urination Disorders; Urological Manifestations; Diabetes Mellitus; Diabetes Complications; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hypertension; Renal Insufficiency, Chronic; Diabetic Nephropathies; Proteinuria; Albuminuria
• Other Study ID Numbers: MLS-101-206

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