Trial on the Safety and Efficacy of MLS-101 in Patients With Uncontrolled Hypertension
Condition: Hypertension, Renal
MeSH terms: Hypertension, Renal; Hypertension
Intervention: MLS-101 (Part I); Placebo (Part I); Placebo (Part II); MLS-101 (Part II)
Intervention description: MLS-101 tablet(s) by mouth once or twice daily.; Placebo tablet(s) by mouth once or twice daily.; Placebo tablet(s) by mouth once daily.; MLS-101 tablet(s) by mouth once daily.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 200.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Blood pressure; Uncontrolled hypertension; Phase II

Summary:

      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
    

Eligibility criteria:

        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