A Study to Assess the Efficacy and Safety of Lorundrostat in Participants With Obstructive Sleep Apnea and Hypertension

A Phase 2, Multicenter, Randomized, Double Blind, Placebo Controlled, Crossover Study to Evaluate the Efficacy and Safety of Lorundrostat in Participants With Moderate to Severe Obstructive Sleep Apnea and Hypertension

The primary purpose of the study is to assess the effect of lorundrostat taken orally (po) once a day on the Apnea-Hypopnea Index (AHI) in participants with moderate to severe obstructive sleep apnea (OSA) and hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension; Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Lorundrostat; Drug: Placebo

Detailed Description

The study is a randomized, double-blind (DB), placebo controlled, crossover study. A 4-week screening period is followed by two DB 4-week treatment periods separated by a 2-week washout period. Participants must be 18 to 75 years old with moderate to severe OSA, hypertension and meet all applicable eligibility criteria. Participants who are medically prescribed and deemed compliant with positive airway pressure (PAP) therapy for greater than or equal to (>=) 4 hours per night (Continuous PAP [CPAP], or automatic PAP [autoPAP]) and for at least 3 months prior to the study enrollment are eligible for the study. Participants on PAP therapy should comply with PAP therapy for the duration of the study. Participants who are not currently on PAP therapy and not anticipated to start PAP for the duration of the study, are also eligible for the study.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35401
      • The University of Alabama
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Chandler Clinical Trials
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners Inc.
  • California
    • Anaheim, California, United States, 92801
      • Orange County Research Institute
    • Carlsbad, California, United States, 92011
      • The Neurology Center of Southern California - Profound Research, LLC
    • Riverside, California, United States, 92501
      • Probe Clinical Research Corporation
  • Colorado
    • Denver, Colorado, United States, 28037
      • Research Carolina Elite
  • Florida
    • Cutler Bay, Florida, United States, 33189
      • Nouvelle Clinical Research
    • Daytona Beach, Florida, United States, 32117
      • Arrow Clinical Trials
    • Miami, Florida, United States, 33176
      • PharmaDev Clinical Research Institute, LLC
    • Orlando, Florida, United States, 32801
      • CNS Healthcare - Orlando (Clinical Neuroscience Solutions)
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • NeuroTrials Research Inc
    • Rincon, Georgia, United States, 31326
      • Centricity Research Rincon Pulmonology
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Chicago Research Center Inc
  • Maryland
    • Columbia, Maryland, United States, 21045
      • Centennial Medical Group
    • Rockville, Maryland, United States, 20854
      • Velocity Clinical Research, Rockville
  • Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System/Henry Ford Medical Center - Columbus
    • Southfield, Michigan, United States, 48075
      • Revive Research Institute, Inc
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Healthcare Research Network
    • St Louis, Missouri, United States, 63123
      • Clayton Sleep Institute
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Patient First MD
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
  • Oregon
    • Portland, Oregon, United States, 97202
      • Northwest Research Center
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • CNS Healthcare - Memphis (Clinical Neuroscience Solutions - Memphis)
  • Texas
    • Huntsville, Texas, United States, 77340
      • Huntsville Research Institute LLC
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy Research Center
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Body mass index (BMI) ≥ 27 kilograms per meter square (kg/m^2)
2. Previously diagnosed with moderate-to-severe OSA
3. AHI ≥15 events per hour (/hr) prior to Randomization
4. AOBP SBP of ≥130 and less than or equal to (≤) 180 millimeter of mercury (mmHg) and AOBP diastolic blood pressure (DBP) ≥60 and ≤110 mmHg
5. Participants on CPAP or PAP therapy are eligible provided they are on PAP for ≥4 hours per night (documented) and for at least 3 months prior to the study enrollment (documented)
6. Participants not currently on PAP therapy, and not anticipated to start PAP for the duration of the study
7. Fertile male and female participants of childbearing potential, and their partners, must agree to use protocol-defined methods of highly effective contraception from the Screening Visit until 28 days after the last dose of study drug

Exclusion Criteria:

1. Type 2 diabetes mellitus (T2DM) with a glycosylated hemoglobin (HbA1c) greater than (>) 9 percent (%) (>74.9 millimoles per mol [mmol/mol]) at the Screening Visit or history of diabetic ketoacidosis in the 6 months prior to the Screening Visit
2. Participants on a glucagon-like peptide-1 (GLP-1) agonist.
3. Any surgery for sleep apnea or major ear, nose or throat surgery, including tonsillectomy and adenoidectomy within 3 months prior to Screening, or planned during participation in the study or within 1 month of the last study visit.
4. Have diagnosis of central or mixed sleep apnea with % of mixed or central apneas/hypopneas ≥50%, or diagnosis of Cheyne Stokes Respiration
5. Diagnosis of Obesity Hypoventilation Syndrome or daytime hypercapnia
6. Use of bilevel positive airway pressure (BiPAP) therapy.
7. eGFR less than (<) 45 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) at Screening using serum creatinine or cystatin-C
8. History of clinically relevant medical, behavioral, or psychiatric disorder, other than OSA, that is associated with insomnia or excessive sleepiness
9. Diagnosed with Child-Pugh Class C
10. Participants who regularly use caffeine stimulants or participants who are unwilling to reduce intake to 300 mg per day (approximately 3 cups of coffee), for a period of at least 3 days prior to the Screening visit or a sleep study
11. Treatment with MRAs and/or epithelial sodium channel (ENaC) inhibitors within 1 month of the Screening Visit
12. Requirement for nocturnal use of supplemental oxygen
13. Women who are pregnant, plan to become pregnant, or are breastfeeding
14. Unstable or currently symptomatic cardiovascular disease or hospitalization in the 6 months prior to Screening
15. Previously diagnosed, recurrent orthostatic hypotension
16. Current night-shift worker or anticipated to become a night-shift worker for 3 days continuously during the duration of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1: Lorundrostat then Placebo	Drug: Lorundrostat; Lorundrostat tablet.; Drug: Placebo; Lorundrostat matching placebo tablet.
Experimental: Sequence 2: Placebo then Lorundrostat	Drug: Lorundrostat; Lorundrostat tablet.; Drug: Placebo; Lorundrostat matching placebo tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Placebo-adjusted Change From Baseline in AHI at Week 4	Baseline, Week 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Placebo-adjusted Change From Baseline in Nighttime Average Systolic Blood Pressure (SBP) at Week 4	Baseline, Week 4
Placebo-adjusted Change From Baseline in Automated Office Blood Pressure (AOBP) SBP at Week 4	Baseline, Week 4
Placebo-adjusted Change From Baseline in Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10) at Week 4	Baseline, Week 4
Placebo-adjusted Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 4	Baseline, Week 4
Placebo-adjusted Change From Baseline in Patient-Reported Outcomes Measurement Information System - Sleep Disturbance (PROMIS-SD) at Week 4	Baseline, Week 4
Placebo-adjusted Change From Baseline in PROMIS Sleep-Related Impairment (SRI) at Week 4	Baseline, Week 4

Collaborators and Investigators

• Sponsor: Mineralys Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2025
• Primary Completion (Actual): December 17, 2025
• Study Completion (Actual): December 29, 2025

Study Registration Dates

• First Submitted: January 16, 2025
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): January 21, 2025

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Hypertension; Obstructive Sleep Apnea; Sleep Apnea; Hypertensive; Blood Pressure
• Additional Relevant MeSH Terms: Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Hypertension; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
• Other Study ID Numbers: MLS-101-207

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No