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

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