• Provision of written informed consent before any study-specific procedure.

• Male or female patients age 18 to 70 years, inclusive, at the Screening Visit.

• Uncontrolled HTN despite being on a stable regimen of ≥ 2 antihypertensive medications in the following drug classes: ACE-inhibitors, ARBs, beta blockers, calcium channel blockers, mineralocorticoid receptor antagonists, or diuretics. A stable regimen is defined as being on the same medications and the same dose for at least 30 days before screening. A combination pill containing 2 separate classes of antihypertensive drugs is considered 2 antihypertensive medications.

• Mean BP of ≥ 130/80 mm Hga.

• Men and nonpregnant, nonlactating women. Women must be either:

‣ Naturally postmenopausal defined as ≥ 1 year without menses and follicle-stimulating hormone ≥ 40.0 IU/L, or

⁃ Surgically sterile including hysterectomy, bilateral oophorectomy, and/or tubal ligation, or

• Women of childbearing potential must be willing to use 2 acceptable methods of birth control (unless they have agreed to follow the definition of true abstinence). The minimal requirement for adequate contraception should be started the day of Visit T1 (Day 1), continuing during the Treatment Period and for at least 30 days after the last dose of study drug. Acceptable methods of birth control include:

⁃ Oral, implantable, injectable, or topical birth control medications. Note: Oral birth control medication must be started ≥ 30 days before the first dose of treatment in the Placebo Run-in.

⁃ Placement of an intrauterine device with or without hormones.

⁃ Barrier methods including condom or occlusive cap with spermicidal foam or spermicidal jelly.

⁃ Vasectomized male partner who is the sole partner for this patient.

⁃ True abstinence when this is the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.

• Body mass index of 18 to 35 kg/m2.

• Negative prestudy urine drugs of abuse screen (with the exception of tetrahydrocannabinol \[THC\]).

• If taking a PDE5 inhibitor for erectile dysfunction, must be willing to pause use during the study period.

∙ Only patients with uncontrolled HTN on ≥ 2 accepted classes of antihypertensive drugs who continue to satisfy the inclusion criteria above, are \> 80% compliant during the Placebo Run-in dosing of 3 tablets QD of single-blind placebo and have successfully completed the baseline 24 hour ABPM will be randomly assigned to treatment with RTN-001 or matching placebo.

∙ aThe initial BP inclusion criterion will be ≥ 130/80 mm Hg. After approximately 25% of patients (80 patients) have been randomly assigned to study treatment, the actual baseline BP of randomized patients will be reviewed to ensure target distribution of BP at study entry. If the mean baseline SBP is not within the target range of approximately 145 mm Hg, the inclusion criterion may be modified to reflect a higher BP inclusion criterion.