| Eligibility |
Inclusion Criteria:
- 1. Established diagnosis of T2DM for at least 6 months prior to Screening AND an A1C =
7.5% but = 11.0% at Screening.
- 2. Subjects should be on:
- a. Diet and exercise therapy with no oral or injectable glucose lowering therapy
for a period of at least 3 months prior to screening; OR
- b. Diet and exercise therapy with a stable dose of metformin only (=1500 mg or
maximal tolerated dose) for a period of at least 3 months prior to Screening.
- 3. Body mass index (BMI) of 25-40 kg/m2 at Screening and stable weight, with no more
than 5 kg gain or loss in the 3 months prior to Screening.
- 4. Renal function - GFR = 30 ml/min/1.73 m2.
- 5. Females of childbearing potential must:
- a. have a negative serum pregnancy test result at Screening.
- b. agree to avoid becoming pregnant while receiving IP for at least 30 days prior
to IP administration, during the entire study, and for 30 days following their
last dose of IP.
- c. agree to use an acceptable method of contraception at least 30 days prior to
IP administration, during the entire study, and for 30 days following their last
dose of IP. Acceptable methods of contraception are hormonal contraception
(contraceptive pill or injection) PLUS an additional barrier method of
contraception such as a diaphragm, condom, sponge, or spermicide.
- d. In the absence of hormonal contraception, double-barrier methods must be used
which include a combination of any two of the following: diaphragm, condom,
copper intrauterine device, sponge, or spermicide, and must be used for at least
30 days prior to administration of IP, during the entire study, and for 30 days
following their last dose of IP.
- e. Abstinence (relative to heterosexual activity) can be used as the sole method
of contraception if it is consistently employed as the subject's preferred and
usual lifestyle and if considered acceptable by local regulatory agencies and
ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal,
post-ovulation methods, etc.) and withdrawal are not acceptable methods of
contraception.
- f. Females who are not of childbearing potential are defined as:
- i. Postmenopausal (defined as at least 12 months with no menses in women =45
years of age); OR
- ii. Have had a hysterectomy and/or bilateral oophorectomy, bilateral
salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior
to screening; OR
- iii. Have a congenital or acquired condition that prevents childbearing.
Exclusion Criteria:
- Subjects with:
- 1. Type 1 diabetes.
- 2. A history of diabetes mellitus with ketoacidosis or is assessed by the Investigator
as possibly having type 1 diabetes mellitus confirmed by a C-peptide < 0.4 ng/mL (0.13
nmol/L) at Screening.
- 3. Diabetes attributable to other secondary causes (e.g., genetic syndromes, secondary
pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and
post-organ transplant).
- 4. Concomitant treatment involving insulin, and any other inhaled, oral or injectable
antihyperglycemic agents including alpha glucosidase inhibitor, meglitinides,
sulfonylurea, DPP-4 inhibitor, SGLT-2 inhibitor, thiazolidinedione or GLP-1 agonists,
and pramlintide within 2 months prior to Visit 1.
- 5. A history of >2 episodes of severe hypoglycemia within 6 months prior to Screening.
- 6. A history of hypoglycemic unawareness.
- 7. A history of unstable angina or myocardial infarction within 6 months prior to
Screening, New York Heart Association (NYHA) Grade 3 or 4 congestive heart failure
(CHF), valvular heart disease, ventricular cardiac arrhythmia requiring treatment,
pulmonary hypertension, cardiac surgery, coronary angioplasty, stroke or transient
ischemic attack (TIA) within 6 months prior to Screening.
- 8. A history of uncontrolled or untreated severe hypertension defined as systolic
blood pressure above or equal to 160 mmHg and/or diastolic blood pressure above or
equal to 100 mmHg. A single repeat measurement will be permitted.
- 9. Renal dysfunction: GFR < 30 mL/min/1.73 m2.
- 10. Active proliferative retinopathy requiring treatment.
- 11. Psychiatric disorders that, per Investigator judgment, may have impact on the
safety of the subject or interfere with subject's participation or compliance in the
study.
- 12. Laboratory abnormalities at Screening including:
- a. C-peptide < 0.4 ng/mL.
- b. Abnormal serum thyrotropin (TSH) levels below the lower limit of normal or
>1.5X the upper limit of normal; a single repeat test is allowable.
- c. Elevated liver enzymes (alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase (ALP)) >3X the upper limit of
normal; a single repeat test is allowable.
- d. Very high fasting triglyceride levels (>600 mg/dL); a single repeat test is
allowable.
- e. Any relevant abnormality that would interfere with the efficacy or the safety
assessments during study treatment administration.
- 13. Positive history of active liver disease (other than non-alcoholic hepatic
steatosis), primary biliary cirrhosis, or active symptomatic gallbladder disease.
- 14. Positive results for human immunodeficiency virus (HIV) antibodies, hepatitis B
surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus
ribonucleic acid (RNA).
- 15. Patient has active or history of neoplastic disease (except for adequately treated
non-invasive basal cell and/or squamous cell carcinoma or carcinoma in situ of the
cervix) within the past 5 years prior to Baseline.
- 16. Use of the following medications:
- a. History of use of any injectable or inhaled, basal, pre-mixed or prandial
insulin (greater than 7 days) within 6 months prior to Screening.
- b. Administration of thyroid preparations or thyroxine (except in subjects on
stable replacement therapy) within 6 weeks prior to Screening.
- c. Requirements (in the last 12 months), or may require, systemic (oral,
intravenous, intramuscular) glucocorticoid therapy for more than 2 weeks during
the study period. Intra-articular and/or topical corticosteroids are not
considered systemic.
- d. Use of medications known to modify glucose metabolism or to decrease the
ability to recover from hypoglycemia such as oral, parenteral, and
immunosuppressive or immunomodulating agents. Inhaled nasal steroids are
permissible.
- 17. Known allergy to soy.
- 18. Involvement in a weight loss program and is not in the maintenance phase, or
subject has started weight loss medication (e.g., orlistat or liraglutide) within 3
months prior to Screening.
- 19. Prior bariatric surgery.
- 20. Subject is pregnant or breast-feeding.
- 21. Subject is a user of recreational or illicit drugs or has had a recent history
(within 1 year of Screening) of drug or alcohol abuse or dependence. (Note: Alcohol
abuse includes heavy Oramed Ltd. Protocol No. ORA-D-013-2 Phase 3 Clinical Study
October 12, 2020 Page 12 alcohol intake as defined by >3 drinks per day or >14 drinks
per week or binge drinking) at Screening. Occasional intermittent use of cannabinoid
products will be allowed provided that no cannabinoid products have been used during
the 1 week prior to each visit.
- 22. Contraindications to metformin use as per label.
- 23. A history of gastrointestinal disorders (e.g. hypochlorhydria) with the potential
to interfere with drug absorption.
- 24. Any condition or other factor (at the Investigator's discretion) that is deemed
unsuitable for subject enrollment into the study.
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