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

NCT06150924 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: MLS-101-206
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 44

Brief Summary

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.

Conditions

Chronic Kidney Disease

Keywords

Albuminuria; Arterial hypertension; Hypertension; Proteinuria; Diabetic nephropathy; Chronic Kidney Disease; Aldosterone Synthase Inhibitor

Outcome Measures

Primary Outcomes (2)

• Placebo-adjusted change from baseline in automated office blood pressure (AOBP) systolic blood pressure (SBP) at Week 4

  baseline to Week 4

• Incidence and severity of adverse events (AEs)

  baseline to Week 14

Other Outcomes (9)

• 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

Study Arms (2)

Cohort 1

EXPERIMENTAL

Drug: Lorundrostat 25mg+SGLT2i QD, Washout, Placebo+SGLT2i QD

Cohort 2

EXPERIMENTAL

Drug: Placebo QD + SGLT2i QD, Washout, Lorundrostat 25mg+SGLT2i QD

Interventions

Lorundrostat 25mg+SGLT2i QD, Washout, Placebo+SGLT2i QD DRUG

Period 1 - Lorundrostat 25mg QD + SGLT2i QD 4 weeks; Washout - Placebo QD + SGLT2i QD 4 weeks; Period 2 - Placebo QD + SGLT2i QD 4 weeks

Cohort 1

Placebo QD + SGLT2i QD, Washout, Lorundrostat 25mg+SGLT2i QD DRUG

Period 1 - Placebo QD + SGLT2i QD 4 weeks; Washout - Placebo QD + SGLT2i QD 4 weeks; Period 2 - Lorundrostat 25mg + SGLT2i QD 4 weeks

Cohort 2

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Subjects with known hypersensitivity to lorundrostat or any of its respective excipients
• Subjects with known hypersensitivity to dapagliflozin or any of its respective excipients (subjects beginning dapagliflozin only)
• At Screening, serum potassium \>5.0 mmol/L
• History of clinically significant hyponatremia within 1 year prior to Screening
• 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
• 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
• Medical history of advanced liver disease, including cirrhosis
• Medical history of active autoimmune disease or recent (within 30 days) or anticipated need for immunosuppressive therapy
• Diabetes mellitus with a glycosylated hemoglobin (HbA1c) \>10% (\>86 mmol/mol) at Screening

Sponsors & Collaborators

• Mineralys Therapeutics Inc.: lead

Study Sites (44)

Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thunderbird Office

Glendale, Arizona, 85306, United States

Location

Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thomas Office

Phoenix, Arizona, 85016, United States

Location

Balboa Nephrology Medical Group, Inc. (BNMG) - California Institute of Renal Research (CIRR) - Chula Vista

Chula Vista, California, 91910, United States

Location

Balboa Nephrology Medical Group, Inc. (BNMG) - El Centro

El Centro, California, 92243, United States

Location

Amicis Research Center - Granada Hills

Granada Hills, California, 91344, United States

Location

Balboa Nephrology Medical Group, Inc. (Bnmg) - La Mesa

La Mesa, California, 91942-3059, United States

Location

Academic Medical Research Institute (AMRI) - Los Angeles

Los Angeles, California, 90022, United States

Location

Amicis Research Center

Northridge, California, 91324, United States

Location

Amicis Research Center - Vacaville

Vacaville, California, 95687-3560, United States

Location

Colorado Kidney Care (Denver Nephrology) - Denver Office

Denver, Colorado, 80218-1216, United States

Location

Qway Research

Coconut Grove, Florida, 33133, United States

Location

Indago Research and Health Center

Hialeah, Florida, 33012, United States

Location

Elixia Pines, LLC

Hollywood, Florida, 33024, United States

Location

Elixia Central Florida, LLC

Orlando, Florida, 32806, United States

Location

Infigo Clinical Research, Llc

Sanford, Florida, 32771, United States

Location

Genesis Clinical Research - Tampa

Tampa, Florida, 33614, United States

Location

Palm Beach Diabetes and Endocrine Specialists, PA (PBDES) - West Palm Beach Office

West Palm Beach, Florida, 33401, United States

Location

American Clinical Trials Llc

Acworth, Georgia, 30101, United States

Location

Nephrology of the Golden Isles - Brunswick

Brunswick, Georgia, 31520, United States

Location

ClinCept, LLC

Columbus, Georgia, 32896, United States

Location

Georgia Nephrology, Llc

Lawrenceville, Georgia, 30046-8761, United States

Location

Nephrology Associates of Kentuckiana, PSC (NAK)

Louisville, Kentucky, 40205, United States

Location

Lcms Health University Medical Center New Orleans

New Orleans, Louisiana, 70112-3018, United States

Location

Northwest Louisiana Nephrology, Llc - Shreveport

Shreveport, Louisiana, 71101, United States

Location

Tufts University School of Medicine (Tusm) - Tufts Medical Center (Tmc) (Tufts-New England Medical Center)

Boston, Massachusetts, 02111, United States

Location

Elixia MKC, LLC

Pontiac, Michigan, 48341, United States

Location

Kansas City Kidney Consultants (Arms, Dodge, Robinson, Wilber & Crouch, Inc.) - Kansas City

Kansas City, Missouri, 64111, United States

Location

Seacoast Kidney & Hypertension Specialists - Portsmouth Office

Portsmouth, New Hampshire, 03801, United States

Location

Suny Downstate Medical Center - Parkside Dialysis Center

Brooklyn, New York, 11226-1508, United States

Location

Nephrology Associates, PC

Fresh Meadows, New York, 11365, United States

Location

Nephrology Associates

Fresh Meadows, New York, 11365, United States

Location

Triad Internal Medicine

Asheboro, North Carolina, 27205, United States

Location

Nephrology Associates, Pllc - Winston-Salem

Winston-Salem, North Carolina, 27103, United States

Location

Nephrology Consultants - Oklahoma City

Oklahoma City, Oklahoma, 73116-1516, United States

Location

Columbia Nephrology

Columbia, South Carolina, 29203, United States

Location

Southeast Renal Research Institute

Chattanooga, Tennessee, 37408, United States

Location

Dallas Nephrology Associates (Dna) - Renal Disease Research Institute (Rdri)

Dallas, Texas, 75235, United States

Location

Liberty Research Center

Dallas, Texas, 75237, United States

Location

R&H Clinical Research

Katy, Texas, 27205, United States

Location

E T Nephrology Associates - Lufkin

Lufkin, Texas, 75904, United States

Location

Prx Research

Mesquite, Texas, 75149, United States

Location

Gamma Medical Research, Inc

Mission, Texas, 78572, United States

Location

Chrysalis Clinical Research (CCR)

St. George, Utah, 84790, United States

Location

Mendez Center for Clinical Research, LLC

Woodbridge, Virginia, 22191, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Albuminuria; Hypertension; Proteinuria; Diabetic Nephropathies

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Urination Disorders; Urological Manifestations; Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Design

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

Study Record Dates

• First Submitted: November 17, 2023
• First Posted: November 29, 2023
• Study Start: December 14, 2023
• Primary Completion: February 27, 2025
• Study Completion: April 23, 2025
• Last Updated: July 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (44)