Efficacy and Safety of Lorundrostat Alone, and in Combination With Dapagliflozin in Subjects With Hypertension and Chronic Kidney Disease (CKD) With Albuminuria

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 2 Study to Evaluate the Efficacy and Safety of Lorundrostat Alone, and Lorundrostat in Combination With Dapagliflozin, in Adults With Hypertension and Chronic Kidney Disease With Albuminuria

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Part A - Lorundrostat QD + Dapaglifozin QD
* Drug: Part A - Lorundrostat QD
* Drug: Part B - Lorundrostat QD Open Label


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - Cohort 1<br> | Drug: Part A - Lorundrostat QD + Dapaglifozin QD<br>* 8 weeks of treatment with lorundrostat QD (Dose 1) plus dapaglifozin QD, 4 weeks of placebo QD washout, followed by 8 weeks of treatment with placebo QD.<br>|
| Experimental: Part A - Cohort 2<br> | Drug: Part A - Lorundrostat QD<br>* 8 weeks of treatment with placebo QD, 4 weeks of placebo QD washout, followed by 8 weeks of treatment with lorundrostat QD (Dose 1).<br>|
| Experimental: Part B - Open Label<br> | Drug: Part B - Lorundrostat QD Open Label<br>* 4 weeks of treatment with lorundrostat QD (Dose 2) followed by 4 weeks of treatment with lorundrostat QD (Dose 3) for subjects who meet prespecified criteria.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Change from baseline in automated office blood pressure (AOBP) SBP at Week 8 |  | baseline to Week 8 | 
| Part B: Incidence and severity of AEs |  | baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Change from Week 12 in AOBP SBP at Week 20 |  | Week 12 to Week 20 | 
| Part A: Percent change from baseline in 24-hour urine albumin to creatinine ratio (UACR) at Week 8 |  | baseline to Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Proteinuria, Diabetic nephropathy, Albuminuria, Arterial hypertension, Chronic Kidney Disease, Aldosterone Synthase Inhibitor