Trial on the Safety and Efficacy of MLS-101 in Patients With Uncontrolled Hypertension

Overview

A randomized, double-blind, placebo-controlled, dose-ranging, Phase II study to evaluate the safety, efficacy, and tolerability of MLS-101 in Subjects With Uncontrolled Hypertension

Full Title of Study: “A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Multicenter Phase 2 Study to Evaluate the Safety, Efficacy, and Tolerability of MLS-101 in Subjects With Uncontrolled Hypertension”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: September 7, 2022

Interventions

  • Drug: MLS-101 (Part I)
    • MLS-101 tablet(s) by mouth once or twice daily.
  • Other: Placebo (Part I)
    • Placebo tablet(s) by mouth once or twice daily.
  • Other: Placebo (Part II)
    • Placebo tablet(s) by mouth once daily.
  • Drug: MLS-101 (Part II)
    • MLS-101 tablet(s) by mouth once daily.

Arms, Groups and Cohorts

  • Placebo Comparator: Placebo (Part I)
    • Placebo tablet(s) by mouth once or twice daily.
  • Experimental: Dose 1 (Part I)
    • MLS-101 tablet(s) by mouth once or twice daily.
  • Experimental: Dose 2 (Part I)
    • MLS-101 tablet(s) by mouth once or twice daily.
  • Experimental: Dose 3 (Part I)
    • MLS-101 tablet(s) by mouth once or twice daily.
  • Placebo Comparator: Placebo (Part II)
    • Placebo tablet(s) by mouth once daily.
  • Experimental: Dose (Part II)
    • MLS-101 tablet(s) by mouth once daily.

Clinical Trial Outcome Measures

Primary Measures

  • Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo
    • Time Frame: 8 Weeks
    • The primary outcome was defined as the change in office-measured (mean of last 2 of 5 unattended measurements using an automated oscillometric sphygmomanometer device after approximately 5 minutes of rest in the seated position) SBP from baseline to the end of Study Week 8. The primary efficacy analysis was performed using a mixed model repeated measures (MMRM) approach with defined fixed effects per the statistical analysis plan. A least-square estimate of the mean difference between each dose group and the placebo group is provided for Week 8.

Secondary Measures

  • Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT)
    • Time Frame: 8 Weeks
    • The ABPM SBP was measured at baseline and EoT. Change in ABPM-derived mean SBP and DBP from baseline to EoT was analyzed using an ANCOVA with a term for treatment group and a baseline mean 24-hour value as a covariate.
  • Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP)
    • Time Frame: 8 weeks
    • Change in office-measured (average of last 2 of 5 unattended measurements using an automated oscillometric sphygmomanometer device after approximately 5 minutes of rest in the seated position) DBP from baseline to the end of study at week 8.
  • Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8
    • Time Frame: 8 Weeks
    • Each participant was assessed as a success if the Week 8 value for SBP was ≤130 mmHg and DBP ≤80 mmHg; subjects not meeting both these thresholds were assessed as a failure. Subjects missing an assessment at Week 8 or who received rescue medications were also considered failures.

Participating in This Clinical Trial

Inclusion Criteria

1. Male and nonpregnant, nonlactating female subjects ≥ 18 years of age. 2. Written informed consent Health Insurance Portability and Accountability Act authorization, and local patient privacy required documentation for this study have been obtained 3. Automated office blood pressure (AOBP) with SBP ≥ 130 mm Hg 4. Background antihypertensive treatment of ≥ 2 drugs 5. Serum cortisol ≥ 18 mcg/dL Exclusion Criteria:

1. Concomitant use of epithelial sodium channel inhibitors or mineralocorticoid receptor antagonists 3. Subjects with hypokalemia 4. Subjects with hyperkalemia 5. Subjects with serum cortisol < 3 mcg/dL 6. Subjects with serum sodium < 135 mEq/L 7. Subjects with estimated glomerular filtration rate < 60 mL/min/1.73m2 8. Subjects with type 1 or uncontrolled (hemoglobin A1c ≥ 9%) type 2 diabetes mellitus 9. Subjects with body mass index > 40 kg/m2 10. Subjects with unstable angina 11. Subjects with SBP ≥ 175 mm Hg or DBP ≥ 100 mm Hg for Part 1 and SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg for Part 2 at Pre-Screening, Screening/Start of Placebo Run-in, or Randomization 12. Subjects with a decrease in SBP ≥ 20 mm Hg or DBP ≥ 10 mm Hg from sitting to standing position at screening 13. Subjects who, in the opinion of the investigator, have suspected nonadherence to antihypertensive treatment 14. Subjects who, in the opinion of the investigator, have any major medical illness or symptoms 15. Subjects who, in the opinion of the investigator, have any acute or chronic medical or psychiatric condition 16. Subjects undergoing treatment with any of the following medications: 1. Topical corticoids 2. Sympathomimetic decongestants 3. Theophylline 4. Phosphodiesterase type 5 inhibitors 5. NSAIDs 6. Intramuscular steroids 7. Estrogen 8. Cytochromes 9. Strong CYP3A and CYP3A4 inducers 17. Subjects with known hypersensitivity to MLS-101 or any of the excipients 18. Subjects who are night-shift workers

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mineralys Therapeutics Inc.
  • Provider of Information About this Clinical Study
    • Sponsor

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