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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Hypertension, Renal

Intervention / Treatment
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* Drug: MLS-101 (Part I)
* Other: Placebo (Part I)
* Other: Placebo (Part II)
* Drug: MLS-101 (Part II)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and nonpregnant, nonlactating female subjects ≥ 18 years of age. Written informed consent Health Insurance Portability and Accountability Act authorization, and local patient privacy required documentation for this study have been obtained Automated office blood pressure (AOBP) with SBP ≥ 130 mm Hg Background antihypertensive treatment of ≥ 2 drugs 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: Topical corticoids Sympathomimetic decongestants Theophylline Phosphodiesterase type 5 inhibitors NSAIDs Intramuscular steroids Estrogen Cytochromes 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (Part I)<br>Placebo tablet(s) by mouth once or twice daily. | Other: Placebo (Part I)<br>* Placebo tablet(s) by mouth once or twice daily.<br>|
| Experimental: Dose 1 (Part I)<br>MLS-101 tablet(s) by mouth once or twice daily. | Drug: MLS-101 (Part I)<br>* MLS-101 tablet(s) by mouth once or twice daily.<br>|
| Experimental: Dose 2 (Part I)<br>MLS-101 tablet(s) by mouth once or twice daily. | Drug: MLS-101 (Part I)<br>* MLS-101 tablet(s) by mouth once or twice daily.<br>|
| Experimental: Dose 3 (Part I)<br>MLS-101 tablet(s) by mouth once or twice daily. | Drug: MLS-101 (Part I)<br>* MLS-101 tablet(s) by mouth once or twice daily.<br>|
| Placebo Comparator: Placebo (Part II)<br>Placebo tablet(s) by mouth once daily. | Other: Placebo (Part II)<br>* Placebo tablet(s) by mouth once daily.<br>|
| Experimental: Dose (Part II)<br>MLS-101 tablet(s) by mouth once daily. | Drug: MLS-101 (Part II)<br>* MLS-101 tablet(s) by mouth once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study-Wide Change in Systolic Blood Pressure | Overall changes in SBP | 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-Hour Ambulatory Systolic and Diastolic Blood Pressure | Overall changes in ambulatory blood pressure outcomes | 8 Weeks | 
| Weekly Changes in Systolic and Diastolic Blood Pressure | Week-to-week changes in SBP and DBP | 8 Weeks | 
| Study-Wide Change in Diastolic Blood Pressure | Overall changes in DBP | 8 Weeks | 
| Proportion of Subjects with ≤ 130/80 mm Hg by End of Study | Cohort-wide changes in blood pressure outcomes | 8 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood pressure, Uncontrolled hypertension, Phase II