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

Mineralys Therapeutics

Status and phase: Active, not recruiting; 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 an end of study (EoS) visit, which will occur after end of treatment (EoT), to complete their participation in the study.

Enrollment: 1,083 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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1,083 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