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: Enrolling; 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), administered on a background of a standardized anti-hypertensive (AHT) medication regimen, in subjects with uncontrolled and/or treatment-resistant hypertension.

Full description

This study is a Phase 2 trial to evaluate the blood pressure-lowering effects of lorundrostat (an aldosterone synthase inhibitor), administered on a background of a standardized anti-hypertensive (AHT) medication regimen, in subjects with uncontrolled and/or treatment-resistant hypertension.

The study consists of a standardized AHT regimen run-in phase followed by a randomized, double-blind, placebo-controlled, parallel arm phase, after which subjects will enter a washout period ending with an end of study (EoS) visit. Subjects may be offered the opportunity to participate in an open-label extension (OLE). Any subject electing to not participate in the OLE will undergo an end of study (EoS) visit to complete their participation in the study.

The study will be conducted at approximately 75-100 sites across the United States.

Enrollment: 261 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
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

---

261 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