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

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

• Concomitant use of epithelial sodium channel inhibitors or mineralocorticoid receptor antagonists

• Subjects with hypokalemia

• Subjects with hyperkalemia

• Subjects with serum cortisol < 3 mcg/dL

• Subjects with serum sodium < 135 mEq/L

• Subjects with estimated glomerular filtration rate < 60 mL/min/1.73m2

• Subjects with type 1 or uncontrolled (hemoglobin A1c ≥ 9%) type 2 diabetes mellitus

• Subjects with body mass index > 40 kg/m2

• Subjects with unstable angina

• 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

• Subjects with a decrease in SBP ≥ 20 mm Hg or DBP ≥ 10 mm Hg from sitting to standing position at screening

• Subjects who, in the opinion of the investigator, have suspected nonadherence to antihypertensive treatment

• Subjects who, in the opinion of the investigator, have any major medical illness or symptoms

• Subjects who, in the opinion of the investigator, have any acute or chronic medical or psychiatric condition

• 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

• Subjects with known hypersensitivity to MLS-101 or any of the excipients

• Subjects who are night-shift workers