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

Mineralys Therapeutics

Status and phase: Enrolling; Phase 3

Conditions: Hypertension

Treatments: Drug: Placebo; Drug: lorundrostat Dose 2; Drug: lorundrostat Dose 1

Study type: Interventional

Funder types: Industry

Identifiers

NCT06153693

MLS-101-301

Details and patient eligibility

About

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.

Full 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 run-in 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.

Enrollment: 1,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. At least 18 years of age at the time of signing the informed consent form (ICF)
2. 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
3. Taking between 2 and 5 AHT medications,
4. History of hypertension lasting at least 6 months prior to Screening
5. Body mass index (BMI) of ≥18 kg/m2 at Screening

Exclusion criteria

1. Women who are pregnant, plan to become pregnant, or are breastfeeding
2. 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
3. eGFR <45 mL/min/1.73m2 at Screening, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
4. Serum potassium >5.0 mmol/L at Screening or >4.8 mmol/L at Randomization
5. Serum sodium <135 mmol/L (corrected for hyperglycemia) at Screening.
6. History of heart failure, myocardial infarction, stroke, or transient ischemic attack within 6 months prior to the Screening Visit.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,000 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo once daily (QD) for 12 weeks

Treatment:

Drug: Placebo

Dose 1

Experimental group

Description:

50 mg lorundrostat Dose 1 once daily (QD) for 12 weeks

Treatment:

Drug: lorundrostat Dose 1

Dose 2

Experimental group

Description:

50 mg lorundrostat Dose 1 once daily (QD) for 6 weeks then 100 mg lorundrostat Dose 2 once daily (QD) for 6 weeks for subjects who meet prespecified criteria

Treatment:

Drug: lorundrostat Dose 2