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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thunderbird Office, Glendale, Arizona, United States

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Major Inclusion Criteria:

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 Exclusion Criteria:

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

Treatment and study plan

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

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

Primary outcomes

Placebo-adjusted Change From Baseline in Automated Office Blood Pressure (AOBP) Systolic Blood Pressure (SBP) at Week 4

Time frame: Baseline to Week 4

Sponsors and collaborators

Lead sponsor

Mineralys Therapeutics Inc.

Industry

Registry information

Official study 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

Important dates

Study start: 2023
Primary completion: 2025
Study completion: 2025
First posted: Nov 29, 2023
Registry last updated: Jun 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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