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

Chronic Kidney Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06150924
• Other study ID #: MLS-101-206
• Status: Recruiting
• Phase: Phase 2
• Start date: December 14, 2023
• Est. completion date: January 2025

Study information

• Verified date: March 2024
• Source: Mineralys Therapeutics Inc.
• Contact: Maghan McCormick
• Phone: 1-888-378-6240
• Email: mmcormick[@]mineralystx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Major Inclusion Criteria:

1. At Screening, UACR of 300-3500 mg/g, inclusive

2. At Screening, eGFRs of:

Part A: =45 and <90 mL/min/1.73 m2 Part B: =30 and <45 mL/min/1.73 m2

3. At Screening, AOBP SBP of 135-180 mmHg, inclusive

4. AOBP SBP of 135-160 mmHg, inclusive, at Randomization (Part A) or Week 0 visit (Part B)

5. On a stable treatment with an ACEi or ARB for at least 2 months prior to Screening

6. At Screening, body mass index (BMI) of 18-45 kg/m2, inclusive

Major Exclusion Criteria:

Part A only:

1. Subjects with known hypersensitivity to dapagliflozin or any of its respective excipients

2. 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:

1. Diabetes mellitus with a glycosylated hemoglobin (HbA1c) >9% (>74.9 mmol/mol) at Screening

2. Medical history of active autoimmune disease or recent or anticipated need for immunosuppressive therapy

3. 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

4. Medical history of advanced liver disease, including cirrhosis

5. History of adrenal insufficiency or an abnormal ACTH stimulation test within 1 year prior to Screening

6. 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.

Related Conditions & MeSH terms

• Albuminuria
• Chronic Kidney Disease
• Hypertension
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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.
• 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).
• 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.

Locations

Country	Name	City	State
United States	Triad Internal Medicine	Asheboro	North Carolina
United States	Tufts University School of Medicine (Tusm) - Tufts Medical Center (Tmc) (Tufts-New England Medical Center)	Boston	Massachusetts
United States	Nephrology of the Golden Isles - Brunswick	Brunswick	Georgia
United States	Southeast Renal Research Institute	Chattanooga	Tennessee
United States	Balboa Nephrology Medical Group, Inc. (BNMG) - California Institute of Renal Research (CIRR) - Chula Vista	Chula Vista	California
United States	Qway Research	Coconut Grove	Florida
United States	ClinCept, LLC	Columbus	Georgia
United States	Dallas Nephrology Associates (Dna) - Renal Disease Research Institute (Rdri)	Dallas	Texas
United States	Balboa Nephrology Medical Group, Inc. (BNMG) - El Centro	El Centro	California
United States	Nephrology Associates	Fresh Meadows	New York
United States	Nephrology Associates, PC	Fresh Meadows	New York
United States	Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thunderbird Office	Glendale	Arizona
United States	Elixia Pines, LLC	Hollywood	Florida
United States	Kansas City Kidney Consultants (Arms, Dodge, Robinson, Wilber & Crouch, Inc.) - Kansas City	Kansas City	Missouri
United States	R&H Clinical Research	Katy	Texas
United States	Academic Medical Research Institute (AMRI) - Los Angeles	Los Angeles	California
United States	Nephrology Associates of Kentuckiana, PSC (NAK)	Louisville	Kentucky
United States	E T Nephrology Associates - Lufkin	Lufkin	Texas
United States	Gamma Medical Research, Inc	Mission	Texas
United States	Elixia Central Florida, LLC	Orlando	Florida
United States	Arizona Kidney Disease & Hypertension Centers (AKDHC) - Thomas Office	Phoenix	Arizona
United States	Elixia MKC, LLC	Pontiac	Michigan
United States	Seacoast Kidney & Hypertension Specialists - Portsmouth Office	Portsmouth	New Hampshire
United States	Chrysalis Clinical Research (CCR)	Saint George	Utah
United States	Northwest Louisiana Nephrology, Llc - Shreveport	Shreveport	Louisiana
United States	Genesis Clinical Research - Tampa	Tampa	Florida
United States	Palm Beach Diabetes and Endocrine Specialists, PA (PBDES) - West Palm Beach Office	West Palm Beach	Florida
United States	Nephrology Associates, Pllc - Winston-Salem	Winston-Salem	North Carolina
United States	Mendez Center for Clinical Research, LLC	Woodbridge	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Mineralys Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Change from baseline in automated office blood pressure (AOBP) SBP at Week 8		baseline to Week 8
Primary	Part B: Incidence and severity of AEs		baseline to Week 8
Secondary	Part A: Change from Week 12 in AOBP SBP at Week 20		Week 12 to Week 20
Secondary	Part A: Percent change from baseline in 24-hour urine albumin to creatinine ratio (UACR) at Week 8		baseline to Week 8