Clinical trial NCT06150924: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Kidney Disease
Keywords: Albuminuria
Arterial hypertension
Hypertension
Proteinuria
Diabetic nephropathy
Chronic Kidney Disease
Aldosterone Synthase Inhibitor
Lead sponsor: Mineralys Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-11-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Placebo-adjusted change from baseline in automated office blood pressure (AOBP) systolic blood pressure (SBP) at Week 4
timeFrame: baseline to Week 4
measure: Incidence and severity of adverse events (AEs)
timeFrame: baseline to Week 14
Secondary outcomes:
Other outcomes:
measure: Placebo-adjusted percent change from baseline in 24-hour urine albumin at Study Week 4
timeFrame: baseline to Study Week 4
measure: Placebo-adjusted change from baseline in AOBP diastolic blood pressure (DBP) at Study Week 4
timeFrame: Study Week 4
measure: Change from baseline in AOBP SBP at Study Week 4 lorundrostat treatment periods
timeFrame: Study Week 4
measure: Percent change from baseline in 24-hour urine albumin at Study Week 4 in lorundrostat treatment periods
timeFrame: baseline to Study Week 4
measure: Placebo-adjusted percent change from baseline in 24-hour urine protein Study Week 4
timeFrame: baseline to Study Week 4
measure: Placebo-adjusted percent change from baseline in urine albumin to creatinine ratio (UACR) at Study Week 4
timeFrame: baseline to Study Week 4
measure: Change in biomarkers from baseline to Study Week 4 in lorundrostat treatment periods
timeFrame: baseline to Study Week 4
measure: Placebo-adjusted percent change in estimated glomerular filtration rate (eGFR) from baseline to Study Week 4
timeFrame: baseline to Study Week 4
measure: Percent change in eGFR from Study Week 4 to Study Week 8
timeFrame: Study Week 4 to Study Week 8
Locations:
city: Glendale
country: United States
facility: Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thunderbird Office
state: Arizona
city: Phoenix
country: United States
facility: Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thomas Office
state: Arizona
city: Chula Vista
country: United States
facility: Balboa Nephrology Medical Group, Inc. (BNMG) - California Institute of Renal Research (CIRR) - Chula Vista
state: California
city: El Centro
country: United States
facility: Balboa Nephrology Medical Group, Inc. (BNMG) - El Centro
state: California
city: Granada Hills
country: United States
facility: Amicis Research Center - Granada Hills
state: California
city: La Mesa
country: United States
facility: Balboa Nephrology Medical Group, Inc. (Bnmg) - La Mesa
state: California
city: Los Angeles
country: United States
facility: Academic Medical Research Institute (AMRI) - Los Angeles
state: California
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Vacaville
country: United States
facility: Amicis Research Center - Vacaville
state: California
city: Denver
country: United States
facility: Colorado Kidney Care (Denver Nephrology) - Denver Office
state: Colorado
city: Coconut Grove
country: United States
facility: Qway Research
state: Florida
city: Hialeah
country: United States
facility: Indago Research and Health Center
state: Florida
city: Hollywood
country: United States
facility: Elixia Pines, LLC
state: Florida
city: Orlando
country: United States
facility: Elixia Central Florida, LLC
state: Florida
city: Sanford
country: United States
facility: Infigo Clinical Research, Llc
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Research - Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Diabetes and Endocrine Specialists, PA (PBDES) - West Palm Beach Office
state: Florida
city: Acworth
country: United States
facility: American Clinical Trials Llc
state: Georgia
city: Brunswick
country: United States
facility: Nephrology of the Golden Isles - Brunswick
state: Georgia
city: Columbus
country: United States
facility: ClinCept, LLC
state: Georgia
city: Lawrenceville
country: United States
facility: Georgia Nephrology, Llc
state: Georgia
city: Louisville
country: United States
facility: Nephrology Associates of Kentuckiana, PSC (NAK)
state: Kentucky
city: New Orleans
country: United States
facility: Lcms Health University Medical Center New Orleans
state: Louisiana
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology, Llc - Shreveport
state: Louisiana
city: Boston
country: United States
facility: Tufts University School of Medicine (Tusm) - Tufts Medical Center (Tmc) (Tufts-New England Medical Center)
state: Massachusetts
city: Pontiac
country: United States
facility: Elixia MKC, LLC
state: Michigan
city: Kansas City
country: United States
facility: Kansas City Kidney Consultants (Arms, Dodge, Robinson, Wilber & Crouch, Inc.) - Kansas City
state: Missouri
city: Portsmouth
country: United States
facility: Seacoast Kidney & Hypertension Specialists - Portsmouth Office
state: New Hampshire
city: Brooklyn
country: United States
facility: Suny Downstate Medical Center - Parkside Dialysis Center
state: New York
city: Fresh Meadows
country: United States
facility: Nephrology Associates, PC
state: New York
city: Fresh Meadows
country: United States
facility: Nephrology Associates
state: New York
city: Asheboro
country: United States
facility: Triad Internal Medicine
state: North Carolina
city: Winston Salem
country: United States
facility: Nephrology Associates, Pllc - Winston-Salem
state: North Carolina
city: Oklahoma City
country: United States
facility: Nephrology Consultants - Oklahoma City
state: Oklahoma
city: Columbia
country: United States
facility: Columbia Nephrology
state: South Carolina
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Dallas Nephrology Associates (Dna) - Renal Disease Research Institute (Rdri)
state: Texas
city: Dallas
country: United States
facility: Liberty Research Center
state: Texas
city: Katy
country: United States
facility: R&H Clinical Research
state: Texas
city: Lufkin
country: United States
facility: E T Nephrology Associates - Lufkin
state: Texas
city: Mesquite
country: United States
facility: Prx Research
state: Texas
city: Mission
country: United States
facility: Gamma Medical Research, Inc
state: Texas
city: Saint George
country: United States
facility: Chrysalis Clinical Research (CCR)
state: Utah
city: Woodbridge
country: United States
facility: Mendez Center for Clinical Research, LLC
state: Virginia
Study officials:
References: