Overview
This is a 2-part study evaluating the efficacy and safety of lorundrostat (an aldosterone synthase inhibitor [ASI]) 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) either in combination with dapagliflozin, or alone.
Description
Part A is a double-blind, placebo-controlled, parallel arm study. Part A consists of up to a 2-week Screening period, followed by two 8-week treatment periods (Period 1 and Period 2) separated by a 4-week single-blind washout phase. Part B consists of up to a 2-week Screening period, followed by an open-label, single arm, dose escalation 8-week treatment phase.
Eligibility
Major Inclusion Criteria:
- At Screening, UACR of 300-3500 mg/g, inclusive
- At Screening, eGFRs of:
Part A: ≥45 and <90 mL/min/1.73 m2 Part B: ≥30 and <45 mL/min/1.73 m2
- At Screening, AOBP SBP of 135-180 mmHg, inclusive
- AOBP SBP of 135-160 mmHg, inclusive, at Randomization (Part A) or Week 0 visit (Part B)
- On a stable treatment with an ACEi or ARB for at least 2 months prior to Screening
- At Screening, body mass index (BMI) of 18-45 kg/m2, inclusive
Major Exclusion Criteria:
Part A only:
- Subjects with known hypersensitivity to dapagliflozin or any of its respective excipients
- Previous treatment with dapagliflozin or other sodium-glucose cotransporter 2 inhibitor (SGLT2i) within 4 weeks prior to the Screening Visit
Part A and Part B:
- Diabetes mellitus with a glycosylated hemoglobin (HbA1c) >9% (>74.9 mmol/mol) at Screening
- Medical history of active autoimmune disease or recent or anticipated need for immunosuppressive therapy
- 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
- History of adrenal insufficiency or an abnormal ACTH stimulation test within 1 year prior to Screening
- Use of epithelial sodium channel (ENaC) inhibitors or mineralocorticoid receptor antagonists (MRAs), including but not limited to amiloride, triamterene, spironolactone, eplerenone or finerenone from 4 weeks prior to the Screening Visit and during study participation. With exception of MRAs in primary aldosteronism.
