A Study to Compare ORMD-0801 Once Daily to ORMD-0801 Three Times Daily in Subjects With Type 1 Diabetes
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: ORMD-0801 Treatment A; ORMD-0801 Treatment B; Placebo
Intervention description: Treatment A: 24 mg (16 mg capsule + 8 mg capsule) Once Daily (QD) at bedtime; Treatment B: 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals; Fish oil capsule
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is an open-label crossover study in which all subjects will receive placebo run-in during Period 1 followed by Period 2, where subjects will be randomly assigned to either daily Treatment A (taken at Bedtime) and Treatment B (taken daily before each of three daily meals). At visit 5, the start of Period 3, subjects will stop their treatment (either A or B) and be CROSSED OVER to the other treatment (patients on treatment A during Period 2 will be crossed over to Treatment B and patients who were on Treatment B during Period 2 will be crossed over to Treatment A in Period 3).
Masking: None (Open Label)
Masking description: Open-Label
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study is a Phase 2 randomized, crossover study comparing ORMD-0801 given QD versus TID
      in subjects with T1D. Subjects with T1D will have a screening visit (Visit 1) during which
      they will be required to review and sign the informed consent form. Medical history and
      demographics will be collected. Vital signs will be measured, physical exam will be
      performed, and blood and urine samples will be collected for hematology/chemistry/urinalysis

      Placebo capsules will be given QD at bedtime during placebo run-in period 10 days prior to
      randomization.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects aged 18 and older.

          -  Body mass index (BMI) of 19-30 kg/m2 at Screening and stable weight, with no more than
             5 kg gain or loss in the 3 months prior to Screening.

          -  T1D subjects must have:

               1. A documented history of type 1 diabetes for at least 6 months

               2. Should be on an MDI regimen

               3. C peptide levels of ˂ 0.7 ng/mL

               4. HbA1C ≥ 6.5% to ≤10%

          -  Females of childbearing potential must have a negative serum pregnancy test result at
             Screening.

          -  Females who are not of childbearing potential are defined as:

               1. post-menopausal (defined as at least 12 months with no menses in women ≥45 years
                  of age) or

               2. has had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal
                  ligation or occlusion at least 6 weeks prior to Screening

          -  Subjects who are of childbearing potential must:

             a. agree to remain abstinent from heterosexual activity† or agree to use (or have
             their partner use) acceptable contraception to prevent pregnancy within the projected
             duration of the trial and for 14 days after the last dose of blinded investigational
             product. Two methods of contraception will be used to avoid pregnancy. Acceptable
             combinations of methods include: i. Use of one of the following double-barrier
             methods: diaphragm with spermicide and a condom; cervical cap and a condom; or a
             contraceptive sponge and condom ii. Use of hormonal contraception (any registered and
             marketed contraceptive agent that contains an estrogen and/or a progestational agent
             [including oral, subcutaneous, intrauterine and intramuscular agents, and cutaneous
             patch]) with one of the following: diaphragm with spermicide; cervical cap;
             contraceptive sponge; condom; vasectomy; or IUD. iii. Use of an IUD with one of the
             following: condom; diaphragm with spermicide; contraceptive sponge; vasectomy; or
             hormonal contraception (see above).

        iv. Vasectomy with one of the following: diaphragm with spermicide; cervical cap;
        contraceptive sponge; condom; IUD; or hormonal contraception (see above).

        †Abstinence can be used as the sole method of contraception if it is in line with the
        subject's preferred and usual lifestyle and if considered acceptable by local regulatory
        agencies and ethics committees. Periodic abstinence (e.g., calendar, ovulation,
        sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of
        contraception.

        Exclusion Criteria:

          -  Clinical diagnosis of type 2 diabetes;

          -  Evidence of unawareness of hypoglycemia unawareness, a documented plasma glucose ≤50
             mg/dL in the absence of symptoms of hypoglycemia at Screening.

          -  FPG >300 mg/dL at Screening; a single repeat test is allowable.

          -  Use of the following medications:

               1. Administration of thyroid preparations or thyroxine (except in subjects on stable
                  replacement therapy) within 6 weeks prior to Screening.

               2. 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.

          -  Laboratory abnormalities at Screening including:

               1. Abnormal serum thyrotropin (TSH) levels below the lower limit of normal or >1.5X
                  the upper limit of normal

               2. Elevated liver enzymes (alanine transaminase (ALT), alanine aminotransferase
                  (AST), alkaline phosphatase) >2X the upper limit of normal.

               3. Very high triglyceride levels (>600 mg/dL); a single repeat test is allowable.

               4. Any relevant abnormality that would interfere with the efficacy or the safety
                  assessments during study treatment administration.

          -  Subject has a Screening systolic blood pressure ≥165 mmHg or diastolic blood pressure
             ≥100 mmHg. Subjects will be allowed to take a BP rescue medication.

          -  Any clinically significant ECG abnormality at Screening or cardiovascular disease.
             Clinically significant cardiovascular disease will include:

             a. 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.

          -  Presence of any clinically significant endocrine disease according to the Investigator
             (euthyroid subjects on replacement therapy will be included if the dosage of thyroxine
             is stable for at least six weeks prior to Screening).

          -  Presence of any clinically significant condition (in the opinion of the Investigator)
             that might interfere with the evaluation of study medication, such as significant
             renal, hepatic, gastrointestinal (GI), cardiovascular (CV), immune disease, blood
             dyscrasias or any disorders causing hemolysis or unstable red blood cells, or
             clinically important hematological disorders (i.e. aplastic anemia, myeloproliferative
             or myelodysplastic syndromes, thrombocytopenia) at Screening.

          -  History of gastrointestinal disorders (e.g. hypochlorhydria) with the potential to
             interfere with drug absorption.

          -  Presence or history of cancer within the past 5 years of Screening, with the exception
             of adequately-treated localized basal cell skin cancer or in situ uterine cervical
             cancer.

               1. A subject with a history of malignancy >5 years prior to Screening should have no
                  evidence of residual or recurrent disease.

               2. A subject with a history of melanoma, leukemia, lymphoma, or renal carcinoma is
                  excluded.

          -  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.

          -  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. Subjects who have had bariatric surgery are also excluded.

          -  S ubject is pregnant or breast-feeding.

          -  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.

          -  At the Principal Investigator's discretion, any condition or other factor that is
             deemed unsuitable for subject enrollment into the study.