A Pivotal Study to Evaluate the Efficacy of Lorundrostat in Subjects with Uncontrolled Hypertension on a Standardized Antihypertensive Medication Regimen

Mineralys Therapeutics

Status and phase: Active, not recruiting; Phase 2

Conditions: Hypertension

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05769608

MLS-101-202

Details and patient eligibility

About

A Phase 2 trial to evaluate the blood pressure-lowering effect of lorundrostat an aldosterone synthase inhibitor (ASI), administered as an add-on to a standardized anti-hypertensive (AHT) medication regimen, in subjects with hypertension.

Full description

This study is a Phase 2 trial to evaluate the blood pressure-lowering effects of lorundrostat (an ASI), administered as add-on to a standardized anti-hypertensive (AHT) medication regimen, in subjects with hypertension.

The study consists of a standardized AHT regimen run-in period followed by a randomized, double-blind, placebo-controlled, parallel arm period. Following the double-blind period subjects may be offered the opportunity to participate in an open-label extension (OLE) study. Subjects electing to not participate in the OLE will undergo an end of study (EoS) visit approximately 2 weeks after the last dose of study drug to complete their participation in the study.

Enrollment: 285 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
2. At Screening: AOBP SBP of 140-180 mmHg and AOBP DBP of 65-110 mmHg, or AOBP DBP of 90-110 mmHg
3. 24-hour average ABPM SBP of 130-180 mmHg or 24-hour average ABPM DBP >80 mmHg
4. Taking between 2 and 5 AHT medications, inclusive, at Screening visit.
5. BMI of 18-40 kg/m2 inclusive at Screening

Exclusion criteria

1. eGFR <45 mL/min/1.73 m2 at Screening, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
2. Serum potassium >5.0 mmol/L at Screening or >4.8 mmol/L at Randomization
3. Serum sodium <135 mmol/L at Screening
4. History of heart failure, myocardial infarction, stroke, or transient ischemic attack within 6 months prior to Screening.
5. Diabetes mellitus with a glycosylated hemoglobin (HbA1c) >9% (>74.9 mmol/mol) at Screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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285 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo once daily for 12 weeks

Treatment:

Drug: Placebo

Dose 1

Experimental group

Description:

lorundrostat Dose 1 once daily for 12 weeks

Treatment:

Drug: lorundrostat Dose 1

Dose 2

Experimental group

Description:

lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks

Treatment:

Drug: lorundrostat Dose 2