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A Study to Compare ORMD-0801 Once Daily to ORMD-0801 Three Times Daily in Subjects With Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT04150107
Recruitment Status : Recruiting
First Posted : November 4, 2019
Last Update Posted : November 5, 2019
Sponsor:
Collaborator:
Integrium
Information provided by (Responsible Party):
Oramed, Ltd.

Brief 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.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: ORMD-0801 Phase 2

Detailed Description:

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. Eligible subjects will be scheduled to return to the clinic in 1 week (Visit 2). Subjects fulfilling all inclusion/exclusion criteria will have a CGM placed, provided with a diary, dispensed Placebo capsules and asked to return to the clinic in 10 Days (Visit 3, Day 1) for randomization. At Visit 3, data from CGM will be downloaded and diaries will be collected. Blood samples will be collected in fasting for chemistry and HbA1c. Subjects will be randomized to receive either ORMD-0801 24 mg given once daily at bedtime, or ORMD-0801 8 mg given three times a day, 45-90 minutes before meals.

Subjects will be instructed to continue their normal diet, and to adjust their basal and bolus insulin in the normal fashion. Subjects will be instructed to return to the clinic 10 days before Visit 5 (Visit 4, Day 18). At Visit 4, compliance will be assessed, IMP and diary dispensed and the CGM will be placed. Subjects will be instructed to return to the clinic in 10 days for Visit 5 (Day 28). At Visit 5 a fasting blood sample for chemistry panel and HbA1C will be drawn and after the diary has been collected and the CGM monitor removed, they will be crossed over to the alternate treatment regimen. IMP will be dispensed, and the subject will be asked to return 10 days before Visit 7 for Visit 6 (Day 46). At Visit 6, compliance will be checked, IMP and diary will be dispensed and the CGM will be placed. Subjects will be instructed to return in 10 days for Visit 7 (Day 56). At Visit 7 the CGM will be removed, compliance checked, the diary will be collected, and a blood sample will be drawn for a chemistry panel and HbA1C. A physical examination will be performed, and the subject will exit the study. Subjects will be provided with diaries at Visits 2, 4 and 6, and will be asked to capture the amount of basal and bolus exogenous insulin administered each day and calculate their carbohydrate count for all meals and snacks over the 10-day CGM monitoring period. Diaries will be collected at Visits 3, 5 and 7.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is an open-label crossover study in which all subjects will receive daily Dose A (taken at Bedtime) and daily Dose B (taken before each of three daily meals)
Masking: None (Open Label)
Masking Description: Open-Label
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Open Label Crossover Study to Compare ORMD-0801 Given Once Daily at Bedtime to ORMD-0801 Given Three Times Daily (45-90 Minutes Before Meals) in Subjects With Type 1 Diabetes
Actual Study Start Date : October 17, 2019
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
Drug Information available for: Insulin

Arm Intervention/treatment
Experimental: Treatment A
Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801
Drug: ORMD-0801
Oral Insulin Capsules
Other Name: Oral Insulin

Experimental: Treatment B
Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals
Drug: ORMD-0801
Oral Insulin Capsules
Other Name: Oral Insulin




Primary Outcome Measures :
  1. The amount of basal exogenous insulin utilized over the final 10 days of each treatment period. [ Time Frame: Final ten days of each treatment period (days 46 to 56) ]
    The amount (mg/dL) of basal exogenous insulin utilized over the final 10 days of each treatment period.

  2. The amount of bolus exogenous insulin utilized over the final 10 days of each treatment period [ Time Frame: Final ten days of treatment (Days 46 to 56) ]
    The amount of bolus exogenous insulin utilized over the final 10 days of each treatment period

  3. Calculate the amount (mg/dL) of total exogenous insulin [ Time Frame: Final ten days of treatment (Days 45 to 56) ]
    Calculate the amount (mg/dL) of total exogenous insulin (the sum of basal + bolus exogenous insulin) over the final 10 days of treatment.


Secondary Outcome Measures :
  1. Glucodynamics over the final 10 days of each treatment [ Time Frame: Study days 46 to 56 ]

    Glucodynamics over the final 10 days of each treatment period as measured by CGM:

    1. Time in range 70 - 180 mg/dL
    2. Time < 70 mg/dL
    3. Time >180 mg/dL
    4. Time >250 mg/dL

  2. Measure the total daily non-oral insulin requirements [ Time Frame: Study Days 46 - 56 ]
    Measure the total daily non-oral insulin requirements in units per kilogram (kg) body weight over the last 10 days of each treatment period.

  3. Glucose Coefficient of Variation [ Time Frame: Study Days 46-56 ]
    Glucose Coefficient of Variation

  4. Low Blood Glucose Index (LBGI) [ Time Frame: Study Days 46-56 ]
    Low Blood Glucose Index (LBGI)

  5. Glucose below 70 mg/dL Area Over the Curve (AOC70) [ Time Frame: Study Days 46-56 ]
    Glucose below 70 mg/dL Area Over the Curve (AOC70)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04150107


Contacts
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Contact: Joel Neutel, MD 714-550-9990 Joel.Neutel@integrium.com
Contact: Kevin Seybert 714-550-9990 Kevin.Seybert@integrium.com

Locations
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United States, California
Orange County Research Center Recruiting
Tustin, California, United States, 92780
Contact: Joel Neutel, MD    714-550-9990    Joel.Neutel@integrium.com   
Contact: Kevin Seybert    714-550-9990    Kevin.Seybert@integrium.com   
Sponsors and Collaborators
Oramed, Ltd.
Integrium
Investigators
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Study Director: Miriam Kidron, PhD Oramed Pharmaceuticals, Inc.

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Responsible Party: Oramed, Ltd.
ClinicalTrials.gov Identifier: NCT04150107     History of Changes
Other Study ID Numbers: ORA-D-017
First Posted: November 4, 2019    Key Record Dates
Last Update Posted: November 5, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs