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
- Conditions
- Chronic Kidney Disease
- Interventions
- Drug: Placebo QD + SGLT2i QD, Washout, Lorundrostat 25mg+SGLT2i QDDrug: Lorundrostat 25mg+SGLT2i QD, Washout, Placebo+SGLT2i QD
- Registration Number
- NCT06150924
- Lead Sponsor
- Mineralys Therapeutics Inc.
- 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.
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 60
- 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
Major
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort 2 Placebo QD + SGLT2i QD, Washout, Lorundrostat 25mg+SGLT2i QD - Cohort 1 Lorundrostat 25mg+SGLT2i QD, Washout, Placebo+SGLT2i QD -
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (44)
Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thunderbird Office
🇺🇸Glendale, Arizona, United States
Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thomas Office
🇺🇸Phoenix, Arizona, United States
Balboa Nephrology Medical Group, Inc. (BNMG) - California Institute of Renal Research (CIRR) - Chula Vista
🇺🇸Chula Vista, California, United States
Balboa Nephrology Medical Group, Inc. (BNMG) - El Centro
🇺🇸El Centro, California, United States
Amicis Research Center - Granada Hills
🇺🇸Granada Hills, California, United States
Balboa Nephrology Medical Group, Inc. (Bnmg) - La Mesa
🇺🇸La Mesa, California, United States
Academic Medical Research Institute (AMRI) - Los Angeles
🇺🇸Los Angeles, California, United States
Amicis Research Center
🇺🇸Northridge, California, United States
Amicis Research Center - Vacaville
🇺🇸Vacaville, California, United States
Colorado Kidney Care (Denver Nephrology) - Denver Office
🇺🇸Denver, Colorado, United States
Qway Research
🇺🇸Coconut Grove, Florida, United States
Indago Research and Health Center
🇺🇸Hialeah, Florida, United States
Elixia Pines, LLC
🇺🇸Hollywood, Florida, United States
Elixia Central Florida, LLC
🇺🇸Orlando, Florida, United States
Infigo Clinical Research, Llc
🇺🇸Sanford, Florida, United States
Genesis Clinical Research - Tampa
🇺🇸Tampa, Florida, United States
Palm Beach Diabetes and Endocrine Specialists, PA (PBDES) - West Palm Beach Office
🇺🇸West Palm Beach, Florida, United States
American Clinical Trials Llc
🇺🇸Acworth, Georgia, United States
Nephrology of the Golden Isles - Brunswick
🇺🇸Brunswick, Georgia, United States
ClinCept, LLC
🇺🇸Columbus, Georgia, United States
Georgia Nephrology, Llc
🇺🇸Lawrenceville, Georgia, United States
Nephrology Associates of Kentuckiana, PSC (NAK)
🇺🇸Louisville, Kentucky, United States
Lcms Health University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Northwest Louisiana Nephrology, Llc - Shreveport
🇺🇸Shreveport, Louisiana, United States
Tufts University School of Medicine (Tusm) - Tufts Medical Center (Tmc) (Tufts-New England Medical Center)
🇺🇸Boston, Massachusetts, United States
Elixia MKC, LLC
🇺🇸Pontiac, Michigan, United States
Kansas City Kidney Consultants (Arms, Dodge, Robinson, Wilber & Crouch, Inc.) - Kansas City
🇺🇸Kansas City, Missouri, United States
Seacoast Kidney & Hypertension Specialists - Portsmouth Office
🇺🇸Portsmouth, New Hampshire, United States
Suny Downstate Medical Center - Parkside Dialysis Center
🇺🇸Brooklyn, New York, United States
Nephrology Associates, PC
🇺🇸Fresh Meadows, New York, United States
Nephrology Associates
🇺🇸Fresh Meadows, New York, United States
Triad Internal Medicine
🇺🇸Asheboro, North Carolina, United States
Nephrology Associates, Pllc - Winston-Salem
🇺🇸Winston Salem, North Carolina, United States
Nephrology Consultants - Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Columbia Nephrology
🇺🇸Columbia, South Carolina, United States
Southeast Renal Research Institute
🇺🇸Chattanooga, Tennessee, United States
Dallas Nephrology Associates (Dna) - Renal Disease Research Institute (Rdri)
🇺🇸Dallas, Texas, United States
Liberty Research Center
🇺🇸Dallas, Texas, United States
R&H Clinical Research
🇺🇸Katy, Texas, United States
E T Nephrology Associates - Lufkin
🇺🇸Lufkin, Texas, United States
Prx Research
🇺🇸Mesquite, Texas, United States
Gamma Medical Research, Inc
🇺🇸Mission, Texas, United States
Chrysalis Clinical Research (CCR)
🇺🇸Saint George, Utah, United States
Mendez Center for Clinical Research, LLC
🇺🇸Woodbridge, Virginia, United States