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

Description

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.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).

Trial Eligibility

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

Study Info

Interventions

Locations Recruiting

Interested in joining this trial?

Our dedicated patient navigators are here to guide you through the validation and enrollment process with ease.