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

Sponsor

Mineralys Therapeutics Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06150924

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Drug: Part A - Lorundrostat QD + Dapaglifozin QD Drug: Part A - Lorundrostat QD Drug: Part B - Lorundrostat QD Open Label	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A - Cohort 1	Drug: Part A - Lorundrostat QD + Dapaglifozin QD 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.
Experimental: Part A - Cohort 2	Drug: Part A - Lorundrostat QD 8 weeks of treatment with placebo QD, 4 weeks of placebo QD washout, followed by 8 weeks of treatment with lorundrostat QD (Dose 1).
Experimental: Part B - Open Label	Drug: Part B - Lorundrostat QD Open Label 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.

Arm

Intervention/Treatment

Experimental: Part A - Cohort 1

Drug: Part A - Lorundrostat QD + Dapaglifozin QD

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.

Experimental: Part A - Cohort 2

Drug: Part A - Lorundrostat QD

8 weeks of treatment with placebo QD, 4 weeks of placebo QD washout, followed by 8 weeks of treatment with lorundrostat QD (Dose 1).

Experimental: Part B - Open Label

Drug: Part B - Lorundrostat QD Open Label

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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.