Safety, Pharmacokinetics and Pharmacodynamics of Multiple Oral Bedtime Doses of ORMD-0801 in Adult Patients With Type 2 Diabetes

This is a single-center, Phase II(a), randomized, double-blind, placebo-controlled, parallel
group, inpatient study preceded by a 5-day single-blind outpatient placebo run-in period.

Inclusion Criteria:

- Male or female patients, age 20 to 70 years, inclusive with type 2 diabetes;

- At time of randomization, patients will be treated for their diabetes by diet and
exercise, or by diet, exercise and metformin (>1000 mg/day; any type and regimen).
Patients will have been on a stable regimen of metformin (defined as the same
metformin dose and type) for at least 6 weeks prior to entering the placebo run-in
period. Other anti-diabetic agents will not have been in use for the 6 weeks prior to
entering the placebo run-in period;

- Body Mass Index (BMI) between 25 and 40 kg/m2, inclusive;

- Hemoglobin A1c (HbA1c) between 6.5 -10.5%, inclusive, prior to randomization)

- Fasting plasma glucose greater than or equal to 126 mg/dL (8.3 mmo1/L) prior to
randomization;

- No tobacco or nicotine use within 10 weeks prior to screening;

- Females of child-bearing potential must have a negative serum pregnancy test result
at screening and a negative urine pregnancy test at Visit 3. Females of
non-childbearing potential are defined as postmenopausal who:

1. had more than 24 months since last menstrual cycle with menopausal levels of
follicle stimulating hormone(FSH);

2. are greater than 55 years old; or

3. are surgically menopausal.

Exclusion Criteria:

- Presence of any clinically significant endocrine disease according to the
Investigator;

- Clinical diagnosis of Type 1 diabetes;

- Fasting plasma glucose >260 mg/dL at the end of washout/stabilization/run-in periods;

- Evidence of unawareness of hypoglycemia, a documented plasma glucose ≤50 mg/dL in the
absence of symptoms of hypoglycemia;

- Presence of any clinically significant condition that might interfere with the
evaluation of study medication;

- Presence or history of cancer within the past five years with the exception of
adequately-treated localized basal cell skin cancer or in situ uterine cervical
cancer;

- Laboratory abnormalities at screening including

1. C-peptide < 1.0 ng/mL;

2. Positive pregnancy test in females of childbearing potential (at screening and
start of run-in period);

3. Abnormal serum thyrotropin (TSH) levels > 1.5 times the upper limit of normal;

4. Positive test for hepatitis B surface antigen and/or hepatitis C antibody;

5. Positive test for HIV;

6. Any relevant abnormality interfering with the efficacy or the safety assessments
during study drug administration;

- Use of the following medications

1. History of use of insulin for no more than 1 week in the last 6 months and none
in the last 6 weeks prior to randomization;

2. History of use of aprotinin at any time prior to the screening visit;

3. Administration of anti-diabetic drugs other than metformin within 6 weeks prior
to run-in period;

4. Administration of thiazolidinedione treatment within 3 months prior to
randomization;

5. Administration of thyroid preparations or thyroxine (except in patients on
stable replacement therapy) within 6 weeks prior to screening visit;

6. Administration of systemic long-acting corticosteroids within two months or
prolonged use of other systemic corticosteroids or inhaled corticosteroids
within 30 days prior to screening visit;

7. Use of medications known to modify glucose metabolism or to decrease the ability
to recover from hypoglycemia such as oral, parenteral, and inhaled steroids,
beta blockers (with the exception of beta blocker ophthalmic solutions for
glaucoma or ocular hypertension), and immunosuppressive or immunomodulating
agents.

- History of severe or multiple allergies;

- History of tobacco or nicotine use within 10 weeks prior to screening

- Patient is on a weight loss program and is not in the maintenance phase, or patient
that started weight loss medication within 8 weeks prior to screening;

- Pregnancy or breast-feeding;

- Patient has a screening visit systolic blood pressure of ≥165 mm Hg or diastolic
blood pressure of ≥100 mm Hg. Patients will be allowed to take a BP rescue medication
as long as it does not affect glucose metabolism (e.g., diuretics) or sensation of
hypoglycemia (e.g., beta-blockers);

- Patient is, at the time of signing informed consent, a user of recreational or
illicit drugs or has had a recent history (within the last year) of drug or alcohol
abuse or dependence;

- Elevated liver enzymes (alanine transaminase (ALT), alanine aminotransferase (AST),
alkaline phosphatase) greater than 2 times the upper limit of normal at screening;

- Very high triglyceride level (>600 mg/dL) at screening;

- Any clinically significant ECG abnormality at screening or cardiovascular disease.
Clinically significant cardiovascular disease will include

1. history of stroke, transient ischemic attack, or myocardial infarction within 6
months prior to screening;

2. history of or currently have New York Heart Associate Class II-IV heart failure
prior to screening; or

3. uncontrolled hypertension defined as blood pressure ≥180 mmHg (systolic) or ≥110
mmHG (diastolic) at screening or at Visit 2;

- One or more contraindications to metformin;

- History of gastrointestinal disorders with the potential to interfere with drug
absorption;

At the Principal Investigator's discretion, any condition or other factor that is deemed
unsuitable for patient enrollment into the study