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

Phase 2

Active, not recruiting

• Conditions: Chronic Kidney Disease
• Interventions: Drug: Placebo QD + SGLT2i QD, Washout, Lorundrostat 25mg+SGLT2i QD; Drug: 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).

Study Timeline

• Study First Submitted: 2023-11-17
• Study First Submitted QC: 2023-11-27
• Study First Posted: 2023-11-29
• Study Start: 2023-12-14
• Status Verified: 2024-11
• Last Update Submitted: 2025-02-19
• Last Update Posted: 2025-02-21
• Primary Completion: 2025-05
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

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 & 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

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

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