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

• ClinicalTrials.gov Identifier: NCT05769608
• Recruitment Status: Recruiting
• First Posted: March 15, 2023
• Last Update Posted: April 26, 2024
• Sponsor: Mineralys Therapeutics Inc.
• Information provided by (Responsible Party): Mineralys Therapeutics Inc.

Tracking Information

• First Submitted Date: February 24, 2023
• First Posted Date: March 15, 2023
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: March 13, 2023
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 22, 2023): Change in 24-hour average ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP [ Time Frame: Baseline (Randomization) to Week 12 ]
• Original Primary Outcome Measures (submitted: March 3, 2023): Change in 24-hour mean ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP) from Week 0 (randomization) to Week 12 [ Time Frame: Week 0 - 12 ]

Current Secondary Outcome Measures (submitted: November 22, 2023)

• Change in 24-hour average ABPM SBP from baseline to Week 12, by body mass index (BMI) [ Time Frame: Baseline to Week 12 ]
• Proportion of subjects with 24-hour average ABPM SBP <125 mmHg [ Time Frame: at Week 12 ]
• Change in daytime average ABPM SBP [ Time Frame: Baseline to Week 12 ]
• Change in automated office blood pressure (AOBP) SBP [ Time Frame: Baseline to Week 12 ]
• Change in nighttime average ABPM SBP [ Time Frame: Baseline to Week 12 ]
• Change in AOBP SBP [ Time Frame: Baseline to Week 16 ]
• Change in 24-hour average ABPM SBP from baseline to Week 12, by number of AHT medications in the standardized AHT regimen (2 vs 3) [ Time Frame: Baseline to Week 12 ]

Original Secondary Outcome Measures (submitted: March 3, 2023)

• Change in automated office blood pressure (AOBP) SBP [ Time Frame: Week 0 - 12 ]
• Change in nighttime mean ABPM SBP [ Time Frame: Week 0 - 12 ]
• Change in AOBP diastolic blood pressure (DBP) [ Time Frame: Week 0 - 2 ]
• Proportion of subjects with AOBP SBP ≤130 mmHg [ Time Frame: Week 12 ]
• Proportion of subjects with AOBP ≤130/80 mmHg [ Time Frame: Week 12 ]
• Change in daytime mean ABPM SBP [ Time Frame: Week 0 - 12 ]
• Change in mean ABPM SBP nighttime dip [ Time Frame: Week 0 - 12 ]
• Change in 24-hour mean ABPM DBP [ Time Frame: Week 0 - 12 ]
• Change in nighttime mean ABPM DBP [ Time Frame: Week 0 - 12 ]
• Change in daytime mean ABPM DBP [ Time Frame: Week 0 - 12 ]
• Proportion of subjects with 24-hour ABPM ≤130/80 mmHg [ Time Frame: Week 12 ]
• Proportion of subjects with an ABPM SBP nighttime dip ≥10% [ Time Frame: Week 12 ]
• Change in 24-hour mean central SBP [ Time Frame: Week 0 - 12 ]
• Change in 24-hour mean central DBP [ Time Frame: Week 0 - 12 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Pivotal Study to Evaluate the Efficacy of Lorundrostat in Subjects With Uncontrolled Hypertension on a Standardized Antihypertensive Medication Regimen
• Official Title: A Randomized, Double-Blind, Placebo Controlled, Parallel Arm, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Lorundrostat in Subjects With Uncontrolled Hypertension on a Standardized Medication Regimen
• Brief Summary: 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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
• Condition: Hypertension

Intervention

• Drug: Placebo
  Placebo once daily for 12 weeks
• Drug: lorundrostat Dose 1
  lorundrostat Dose 1 once daily for 12 weeks
• Drug: lorundrostat Dose 2
  lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks for subjects who meet prespecified criteria

Study Arms

• Placebo Comparator: Placebo
  Placebo once daily for 12 weeks
  Intervention: Drug: Placebo
• Experimental: Dose 1
  lorundrostat Dose 1 once daily for 12 weeks
  Intervention: Drug: lorundrostat Dose 1
• Experimental: Dose 2
  lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks
  Intervention: Drug: lorundrostat Dose 2

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 22, 2023): 261
• Original Estimated Enrollment (submitted: March 3, 2023): 300
• Estimated Study Completion Date: October 2024
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Megan McCormick; 518-727-1995; mmccormick@mineralystx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05769608
• Other Study ID Numbers: MLS-101-202
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mineralys Therapeutics Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Mineralys Therapeutics Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Mineralys Therapeutics Inc.
• Verification Date: April 2024