A Study of Modified Release RTN-001 In Patients With Uncontrolled Hypertension

Inclusion Criteria: 1. Provision of written informed consent before any study-specific procedure. 2. Male or female patients age 18 to 75 years, inclusive, at the Screening Visit. 3. Uncontrolled HTN despite being on a stable regimen of 2-5 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. 4. Mean BP of ≥ 135/80 mm Hg. 5. Men and nonpregnant, nonlactating women. Women must be either: * Postmenopausal defined as naturally ≥ 1 year without menses or \< 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. 6. Body mass index of 18 to 35 kg/m2. 7. Negative pre-study urine drugs of abuse screen, except for positive findings attributable to medications that are not prohibited (e.g., tetrahydrocannabinol \[THC\]) if prescribed by a physician for an established medical condition and are on a stable dose for at least 4 weeks prior to Screening Visit (S1). 8. If taking a PDE5 inhibitor, must be willing to pause use during the study period. Exclusion Criteria: 1. Currently enrolled in a study with an investigational product or any other type of medical research within 30 days before randomization. 2. Mean seated SBP \> 175 mm Hg and/or DBP \> 110 mm Hg. 3. Current or planned use of nitrates and/or alpha-blockers or other drugs known to affect BP during the study period. 4. Participants who use PDE5 inhibitors for other indications that cannot or will not refrain from use of PDE5 inhibitors for 7 days before and during their entire period of participation in the study. 5. History of hypotension, fainting spells, blackouts or autonomic dysfunction, including orthostatic hypotension. 6. Known diagnosis of secondary hypertension (e.g. Cushing's Disease or hyperaldosteronism, renal fibrodysplasia, renal artery stenosis, etc., clinically significant aortic stenosis etc.). 7. Active pancreatitis. 8. A history of drug abuse. 9. Abuses alcohol defined as average weekly intake greater than 21 units for males or 14 units for females. One unit is equivalent to a 12 oz beer, 1 measure of spirits, or 1 glass of wine. 10. History or presence of gastrointestinal, hepatic, or renal disease or other conditions that would be known to interfere with the absorption, distribution, metabolism, or excretion of drugs. 11. Recent (within 3 months before the Screening Visit \[Visit S1\]) myocardial infarction; unstable angina leading to hospitalization; uncontrolled, symptomatic atrial fibrillation, or any cardiac arrhythmia that has not been clinically stable for at least 3 months prior to the S1 (stability is defined as the absence of new symptoms related to the arrhythmia and no changes in anti-arrhythmic medication or dosage within the 90 days preceding S1); hemodynamically significant aortic stenosis or other clinically significant left ventricular outflow tract obstruction (eg, hypertrophic obstructive cardiomyopathy), coronary artery bypass graft; percutaneous coronary intervention; carotid surgery or stenting; cerebrovascular accident; transient ischemic attack; endovascular procedure or surgical intervention for peripheral vascular disease; or plans to undergo a major surgical or interventional procedure (eg, percutaneous coronary intervention, coronary artery bypass graft, carotid or peripheral revascularization). Participants with implantable pacemakers or automatic implantable cardioverter defibrillators may be considered if deemed by the Investigator to be stable for the previous 3 months. 12. Uncontrolled hypothyroidism, including thyroid-stimulating hormone \> 1.5 × the upper limit of normal (ULN) at the Screening Visit (Visit S1 or Unscheduled visits prior to the T1 visit); patients stabilized on thyroid replacement therapy for at least 6 weeks before randomization are allowed. 13. Liver disease or dysfunction, including: 1. Positive serology for hepatitis B surface antigen and/or hepatitis C antibodies at the Screening Visit (Visit S1 or Unscheduled visits prior to the T1 visit, or 2. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥ 2 × ULN, and/or total bilirubin (TB) ≥ 2 × ULN at the Screening Visit (Visit S1or Unscheduled visits prior to the T1 visit). If TB ≥ 1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained, and if consistent with Gilbert's syndrome or if the patient has a history of Gilbert's syndrome, the patient may be enrolled in the study. Note: At the discretion of the Investigator, a repeat of ALT and/or AST may be completed before randomization. For those patients who have a repeat ALT and/or AST, the repeat value will be used to determine eligibility. Also, if the patient tests positive for the hepatitis C antibody, but the optional reflexive test for hepatitis C RNA is negative, the patient can be enrolled. 14. Renal dysfunction or glomerulonephritis, including estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula \< 45 mL/min/1.73 m2 at the Screening Visit (Visit S1). 15. Active infection or major illness, other than mild viral illness within 30 days prior to T1 visit; positive for HIV antibody. 16. Gastrointestinal conditions or procedures (including weight loss surgery \[eg, Lap-Band or gastric bypass\]) that may affect drug absorption. 17. Hematologic or coagulation disorders or a hemoglobin level \< 10.0 g/dL at the Screening Visit (Visit S1or Unscheduled visits prior to the T1 visit) or anticipated initiation of erythropoietin-stimulating agents and/or planned transfusion within 2 months after screening 18. Active malignancy, including a malignancy requiring surgery, chemotherapy, and/or radiation in the 5 years before Screening. Nonmetastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ are allowed. 19. Unexplained creatine kinase (CK) \> 3 × ULN at any time before randomization, which is not associated with recent trauma or physically strenuous activity. Patients with an explained CK elevation must have a single repeat CK ≤ 3 × ULN before randomization. 20. Blood donation, participation in multiple blood draws, clinical study, major trauma, blood transfusion, or surgery with or without blood loss within 30 days before randomization. 21. Use of any experimental or investigational drug(s) within 30 days before the Screening Visit (Visit S1) or for at least five t1/2 lives for investigational biologics (whichever is longer). 22. An employee or contractor of the facility conducting the study, or a family member of the principal investigator, co-investigator, or any Sponsor personnel 23. Is unwilling to comply with and complete study procedures or considered by the Investigator to be unsuitable for any other reason that may either place the participant at increased risk during participation or interfere with the interpretation of study outcomes, after reviewing the medical and psychiatric history, physical examination, and laboratory evaluation. 24. A known history of temporary or permanent partial or total vision loss including, but not limited to, participants with non-arteritic anterior ischemic optic neuropathy (NAION). 25. A known history of "crowded" optic disc. 26. A known history of retinitis pigmentosa, a rare genetic eye disease. 27. Unable to refrain from or anticipates the use of: 1. Any prescription or over-the counter drugs or herbal supplements known to be strong inhibitors of CYP3A4 enzymes for 14 days or 5 times the half-life of the product (whichever is longer) prior to the first dose of study drug, throughout the period of dose application, and until the last PK blood draw is collected. 2. Any prescription or over-the counter drugs or herbal supplements known to be significant inducers of CYP enzymes, including St. John's Wort, for 28 days prior to the first dose of study drug, throughout the period of dose application, and until the last PK blood draw is collected. 28. NHYA class III-IV symptoms of heart failure. 29. Has a history of diabetes or suspected diabetes with glycosylated hemoglobin \> 10% or fasting glucose \> 250 mg/dl at Screening Visit (S1).