Efficacy and Safety of Lorundrostat in Subjects With Uncontrolled and Resistant Hypertension

Sponsor

Mineralys Therapeutics Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06153693

Collaborator

(none)

1,000

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a Phase 3 trial to evaluate the BP-lowering effect of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled and resistant hypertension taking between 2 and 5 anti-hypertensive (AHT) medications.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Placebo Drug: lorundrostat Dose 1 Drug: lorundrostat Dose 2	Phase 3

Detailed Description

This study is a Phase 3 trial to evaluate the BP-lowering effect of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled and resistant hypertension taking between 2 and 5 anti-hypertensive (AHT) medications, one of which must be a thiazide or thiazide-like diuretic.

The study consists of a 2-week screening period with a 2-week single-blind placebo period followed by a 12-week randomized, double-blind, placebo-controlled, parallel arm period. Following the randomized period subjects will be offered an opportunity to participate in an open-label extension (OLE) study. Any subject electing to not participate in the OLE will undergo a 2-week end of study (EoS) visit, which will occur after end of treatment (EoT), to complete their participation in the study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo Controlled, Parallel Arm, Multicenter Phase 3 Study to Evaluate the Efficacy and Safety of Lorundrostat in Subjects With Uncontrolled and Resistant Hypertension

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo once daily for 12 weeks	Drug: Placebo Placebo once daily for 12 weeks
Experimental: Dose 1 lorundrostat Dose 1 once daily for 12 weeks	Drug: lorundrostat Dose 1 lorundrostat Dose 1 once daily for 12 weeks
Experimental: Dose 2 lorundrostat Dose 1 once daily for 6 weeks then lorundrostat Dose 2 once daily for 6 weeks for subjects who meet prespecified criteria	Drug: lorundrostat Dose 2 lorundrostat Dose 1 once daily for 6 weeks then lorundrostat Dose 2 once daily for 6 weeks for subjects who meet prespecified criteria

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo once daily for 12 weeks

Drug: Placebo

Placebo once daily for 12 weeks

Experimental: Dose 1

lorundrostat Dose 1 once daily for 12 weeks

Drug: lorundrostat Dose 1

lorundrostat Dose 1 once daily for 12 weeks

Experimental: Dose 2

lorundrostat Dose 1 once daily for 6 weeks then lorundrostat Dose 2 once daily for 6 weeks for subjects who meet prespecified criteria

Drug: lorundrostat Dose 2

lorundrostat Dose 1 once daily for 6 weeks then lorundrostat Dose 2 once daily for 6 weeks for subjects who meet prespecified criteria

Outcome Measures

Primary Outcome Measures

Change from baseline in automated office BP (AOBP) SBP at Week 12 in subjects randomized to lorundrostat [Week 12]
Change from baseline in AOBP SBP at Week 12 in subjects randomized to lorundrostat Dose 1 with escalation to lorundrostat Dose 2 [Week 12]

Secondary Outcome Measures

Proportion of subjects with AOBP SBP <130 mmHg at Week 12 in combined lorundrostat dosages [Week 12]
Change from baseline in AOBP SBP at Week 12 in subjects with uncontrolled hypertension in combined lorundrostat dosages [Week 12]
Change from baseline in AOBP SBP at Week 12 in subjects with resistant hypertension in combined lorundrostat dosages [Week 12]
Change from baseline in AOBP SBP at Week 12 by obesity status in combined lorundrostat dosages [Week 12]
Change from baseline in AOBP SBP at Week 12 in subjects who did not reach SBP control by Week 6 on lorundrostat Dose 1 and were increased to lorundrostat Dose 2 (within-subjects analysis) [Week 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

At least 18 years of age at the time of signing the informed consent form (ICF)
At Screening and Randomization: AOBP SBP of ≥135 and ≤180 mmHg plus AOBP DBP of ≥65 and ≤110 mmHg, or AOBP DBP of ≥90 and ≤110 mmHg
Taking between 2 and 5 AHT medications,
History of hypertension lasting at least 6 months prior to Screening
Body mass index (BMI) of ≥18 kg/m2 at Screening

Exclusion Criteria:

Women who are pregnant, plan to become pregnant, or are breastfeeding
Participation in a study involving any investigational device or small-molecule drug within 4 weeks or 6 months for biologic (antibody) drugs prior to the Screening Visit
eGFR <45 mL/min/1.73m2 at Screening, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
Serum potassium >5.0 mmol/L at Screening or >4.8 mmol/L at Randomization
Serum sodium <135 mmol/L (corrected for hyperglycemia) at Screening.
History of heart failure, myocardial infarction, stroke, or transient ischemic attack within 6 months prior to the Screening Visit.