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

Mineralys Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Chronic Kidney Disease

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06150924

MLS-101-206

Details and patient eligibility

About

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.

Full 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).

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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60 participants in 2 patient groups

Cohort 1

Experimental group

Treatment:

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

Cohort 2

Experimental group

Treatment:

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