A Prospective, Randomized, Double-blind, Placebo Controlled Study to Assess the Impact of ORMD-0801 (Insulin Capsules) on the Exogenous Insulin Requirements of Type 1 Diabetics
Condition: Diabetes Mellitus Type 1
MeSH terms: Diabetes Mellitus, Type 1
Intervention: ORMD-0801 Capsules; Placebo
Intervention description: API (recombinant human insulin USP), in Oramed's proprietary formulation in capsules.; Fish oil capsules, identical in appearance to the experimental intervention.
Intervention MeSH terms: Insulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Diabetes type 1; Oral Insulin; Safety; Tolerability; Phase 2a; Randomized; Blinded; Parallel

Summary:

      This will be a prospective, randomized, double-blind, placebo controlled study. Patients with
      established Type 1 diabetes will be eligible for entry into the study. Eligible patients will
      be screened and those who fulfill all inclusion/exclusion criteria will be admitted to the
      inpatient unit no fewer than 2 days and no more than 7 days after Screening. Patients will
      report to the inpatient unit at 6 a.m. and outfitted with a continuous glucose monitoring
      (CGM) device. Patients will be given standardized meals and snacks for the duration of their
      inpatient visit.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and Females age 18 to 55 years old, inclusive.

          -  Patients must be willing and able to sign informed consent.

          -  Documented history of Type 1 Diabetes for at least 6 months

          -  Females of childbearing potential must have a negative serum pregnancy test at
             screening and a negative urinary screening test following admission to the inpatient
             unit

        Exclusion Criteria:

          -  Presence of any clinically significant endocrine disease according to the Investigator
             (euthyroid patients on replacement therapy will be included if the dosage of thyroxine
             is stable for at least six weeks prior to Screening)

          -  Fasting plasma glucose >260 mg/dL at the end of run-in

          -  Evidence of unawareness of hypoglycemia with 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 (i.e., significant renal, hepatic, gastrointestinal
             (GI), cardiovascular (CV), immune disease).

          -  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:

          -  Positive pregnancy test in females of childbearing potential (at screening and Day -3
             of Visit 2)

          -  Abnormal serum thyrotropin (TSH) levels >1.5X upper limit of normal (ULN)

          -  Positive test for hepatitis B surface antigen and/or hepatitis C antibody

          -  Positive test for HIV

          -  Any relevant abnormality interfering with the efficacy or the safety assessments
             during study drug administration

          -  Use of the following medications:

             o History of use of aprotinin at any time prior to the screening visit (e.g.,
             Trasylol, any type or dose)

          -  Administration of thiazolidinedione [e.g., (Actos (pioglitazone) and Avandia
             (rosiglitazone)] treatment within 3 months prior to randomization.

          -  Administration of thyroid preparations or thyroxine (except in patients on stable
             replacement therapy) within 6 weeks prior to screening visit

          -  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 visit

          -  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), 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, or known allergy to soy or aprotinin.

          -  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 (e.g., orlistat or sibutramine) within 8 weeks
             prior to screening

          -  Pregnancy or breast-feeding

          -  Patient has a screening visit systolic blood pressure of ≥165 mmHg or diastolic blood
             pressure of ≥100 mmHg.

          -  Patient is, at the time of 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. (Note:
             Alcohol abuse includes heavy alcohol intake as defined by >3 drinks per day or >14
             drinks per week, or binge drinking)

          -  Elevated liver enzymes (alanine transaminase (ALT), alanine aminotransferase (AST),
             alkaline phosphatase) greater than 2 times the upper limit of normal (ULN) at
             Screening

          -  Very high triglyceride level (>600 mg/dL) at Screening

          -  Any clinically significant electrocardiogram (ECG) abnormality at screening or
             cardiovascular disease. Clinically significant cardiovascular disease will include:

          -  history of stroke, transient ischemic attack, or myocardial infarction within 6 months
             prior to screening,

          -  history of or currently have New York Heart Associate Class II-IV heart failure prior
             to screening, or

          -  uncontrolled hypertension defined as (duplicate seated reading) blood pressure ≥165
             mmHg (systolic) or ≥100 mmHg (diastolic) at screening or at Visit 2.

          -  History of gastrointestinal disorders (e.g. hypochlorhydria) 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.