A Study to Evaluate the Efficacy and Safety of ORMD-0801 (Oral Insulin) in Patients With Type 2 Diabetes Mellitus

Inclusion Criteria

• Male and female subjects aged 18 and older.
• Established diagnosis of T2DM for at least 6 months prior to Screening, with an HbA1C (glycated hemoglobin) ≥ 7.5%.
• Stable dose of metformin (at least 1500 mg or maximally tolerated dose)/oral antidiabetic (OAD) for a period of at least 3 months prior to screening.
• Taking metformin only or metformin in addition to no more than two of the following: DPP-4 (DiPeptidyl Peptidase-4), SGLT-2 (Sodium-GLucose coTransporter-2), or TZD (Thiazolidinediones).
• Body mass index (BMI) of up to 40 kg/m2 at Screening and stable weight, with no more than 5 kg gain or loss in the 3 months prior to Screening.
• Renal function - eGFR (estimated glomerular filtration rate) > 30 ml/min/1.73 m2
• Females of childbearing potential must have a negative serum pregnancy test result at Screening.

Exclusion Criteria

• Subjects with insulin-dependent diabetes
• has a history of type 1 diabetes mellitus or a history of ketoacidosis, or subject is assessed by the investigator as possibly having type 1 diabetes mellitus confirmed by a C-peptide 2 episodes of severe hypoglycemia within 6 months prior to Screening.
• History of hypoglycemic unawareness (episodes of severe hypoglycemia with seizure or requiring third-party intervention or documented low blood glucose without associated autonomic symptoms)
• Subjects with the following secondary complications of diabetes:
• Active proliferative retinopathy as confirmed by a dilated ophthalmoscopy/retinal photography examination performed (by a qualified person as per the country legislation) within 6 months prior to Screening.
• Renal dysfunction: eGFR 1.5X the upper limit of normal
• Elevated liver enzymes (alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase) >2X the upper limit of normal.
• Very high triglyceride levels (>600 mg/dL); a single repeat test is allowable.
• Any relevant abnormality that would interfere with the efficacy or the safety assessments during the study treatment administration.
• Positive history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic hepatitis B or C, primary biliary cirrhosis, or active symptomatic gallbladder disease.
• Positive history of HIV.
• Use of the following medications:
• History of any basal, pre-mix or prandial insulin (greater than 7 days) within 6 months prior to Screening.
• Administration of thyroid preparations or thyroxine (except in subjects on stable replacement therapy) within 6 weeks prior to Screening.
• Administration of systemic long-acting corticosteroids within two months or prolonged use (more than one week) of other systemic corticosteroids or inhaled corticosteroids (if daily dosage is > 1,000 μg equivalent beclomethasone) within 30 days prior to Screening. Intra-articular and/or topical corticosteroids are not considered systemic.
• Use of medications known to modify glucose metabolism or to decrease the ability to recover from hypoglycemia such as oral, parenteral, and inhaled steroids (as discussed above), and immunosuppressive or immunomodulating agents.
• Known allergy to soy.
• Subject is on a weight loss program and is not in the maintenance phase or subject has started weight loss medication (e.g., orlistat or liraglutide), within 8 weeks prior to Screening.
• Subject has had bariatric surgery.
• Subject is pregnant or breastfeeding.
• 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 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.
• One or more contraindications to metformin as per local label.
• History of gastrointestinal disorders (e.g.