Safety Study of RMJH-111b to Treat Essential Hypertension

This is a phase 1/2, single center, randomized, double-blind, placebo-controlled study of
RMJH-111b in adult subjects with essential hypertension.

Subjects will be taken off their anti-hypertensive medications and undergo a 7-day washout
period. Subjects that remain eligible after the washout period and subjects that do not
require a washout (recently diagnosed or previously diagnosed and off treatment for > 1 week
before starting the study) will receive placebo orally twice a day (bid) for a 3-day run-in
period.

Subjects that remain eligible after the run-in period will be randomized 15:6 (for at total
of 21 randomized subjects) to receive either 440 mg of RMJH-111b or placebo orally bid for a
7-day treatment period. Follow-up assessments will be performed 24 hours and 7 days after
the last dose of study drug.

Subjects will remain in the clinical research unit on a low salt (2.5 g/24 hours) diet for
the run-in period through the 24-hour post treatment assessments.

Inclusion Criteria:

- Male or female, 18-80 years old

- Diagnosed with essential hypertension

- SBP ≥ 150 & ≤ 200 mmHg & DBP ≥ 95 and ≤ 115 mmHg at Day 1 & baseline (pre-dose Day 4)

- Both males & women of child bearing potential (WCBP) agree to use adequate
contraceptive methods while on study

- Willing and able to sign informed consent form (ICF)

- Suitable for participation in the study in the opinion of the Investigator

Exclusion Criteria:

- History of myocardial infarction, congestive heart failure, or stroke within 6 months
of Screening, or evidence of greater than 1st degree heart block or myocardial damage

- History of chronic hepatitis

- Uncontrolled diabetes (hemoglobin A1C ≥ 6.5%) at Screening or Day 1

- Glomerular filtration rate < 60 mL/min at Screening or Day 1

- Serum hypo- or hyper-natremia (≤ 133 & ≥145 meq/L) at Screening or Day 1

- Low serum potassium (≤ 3.3 meq/L) at Screening or Day 1

- Low total serum magnesium (≤ 1.3 mg/dL) or total serum magnesium greater than the
upper limit of normal (2.5 mg/dL) at Screening or Day 1

- Serum uric acid > 6.5 mg/dL for females or >7.5 mg/dL for males at Screening or Day 1

- Absence of patellar reflex (knee jerk) at Day 1-3, or pre-dose Day 4

- Evidence of clinically significant findings at Screening, during the run-in period
(Days 1-3), or at baseline (pre-dose Day 4) which, in the opinion of the Investigator
would pose a safety risk or interfere with appropriate interpretation of safety data

- Malignancy within 5 years of the Screening Visit (with the exception of basal cell
and squamous cell skin carcinoma)

- Major surgery within four weeks prior to Screening

- Presence of a malabsorption syndrome possibly affecting drug absorption (e.g.,
Crohn's disease or chronic pancreatitis)

- Presence of irritable bowel syndrome, ulcerative colitis, or chronic diarrhea

- History of psychotic disorder

- History of alcoholism or drug addiction or current alcohol or drug use that, in the
opinion of the Investigator, will interfere with the subject's ability to comply with
the dosing schedule & study evaluations

- History of any illicit drug use within one year prior to Screening

- Positive drug screen at Screening or at Day 1, except subjects on prescription drugs
that in the opinion of the Investigator will not influence the outcome of the study

- Positive breathalyzer test for blood alcohol content at Screening or at Day 1

- Consumption of more than five cups of caffeinated beverages per day

- Current treatment or treatment within 30 days prior to the first dose of Study Drug
(active or placebo; Day 4) with another investigational drug, or current enrollment
in another clinical trial

- Current treatment or treatment within 10 days prior to the first dose of Study Drug
(active or placebo; Day 4) with any anti-hypertension medication (other than Study
Drug during the treatment period)

- Current treatment or treatment within 30 days prior to the first dose of Study Drug
(active or placebo; Day 4) with magnesium-containing antacids or laxatives, dietary
supplement(s) where the total daily dose of magnesium is greater than 150 mg, central
nervous system depressants, neuromuscular blocking agents, or cardiac glycosides,
lithium-containing drugs, bisphosphonates, sodium polystyrene sulfonate, or
tetracycline/quinolone antibiotics, anti-tumor necrosis factor-alpha drugs, or
phytotherapeutic/herbal/ plant derived preparations

- Known hypersensitivity to magnesium

- Known hypersensitivity to the inactive ingredients in the Study Drug (placebo and
active)

- Positive pregnancy test at Screening or at Day 1, or lactating

- Arm circumference greater than 42 centimeters