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

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ClinicalTrials.gov Identifier: NCT03467932
Recruitment Status : Recruiting
First Posted : March 16, 2018
Last Update Posted : May 24, 2019
Sponsor:
Collaborator:
Integrium
Information provided by (Responsible Party):
Oramed, Ltd.

Brief Summary:
This is a four-way (Participant, Care Provider, Investigator, Outcomes Assessor) masked (blinded) study designed to explore efficacy of ORMD-0801 when given in different regimens across a dose range for up to 12 weeks in subjects with type 2 diabetes mellitus (T2DM).

Condition or disease Intervention/treatment Phase
T2DM (Type 2 Diabetes Mellitus) Drug: Cohort A: ORMD-0801 Drug: Placebo oral capsule Drug: Cohort B: ORMD-0801 Phase 2

Detailed Description:

This study is designed to explore the efficacy of ORMD-0801 when given in different regimens across a dose range for up to 12 weeks in subjects with type 2 diabetes mellitus (T2DM). There are two cohorts in this study. Approximately 360 subjects with T2DM will initially undergo a 2-week, single-blind placebo run-in period (Visits 1 and 2), followed by a 12-week treatment period (Visits 3 through 9). Cohort A will enroll 285 subjects; Cohort B will enroll 75 subjects

For 265 of the 285 subjects of Cohort A, the total 12-week treatment period will include a Part 1"dose escalation" interval (2 weeks, Visits 3 and 4) and a Part 2 stable dose "maintenance" interval (10 weeks, Visits 5 through 9).

In addition, per FDA request, the remaining 20 subjects (of the cohort total of 285 enrolled subjects) will receive excipient-matched placebo in a non-randomized single-blind fashion, TID, according to the same schedule as described above.

For Cohort B (75 of the 360 total subjects), the total 12-week treatment period will include a stable dosing period for both Part 1 (2 weeks, Visits 3 and 4) and Part 2 (10 weeks, Visits 5 through 9).

Cohort A data will be analyzed after Cohort A data collection has been completed (last subject for Cohort A screened on 7 May 2019). Estimated completion for Cohort A is October 2019. Cohort B data will be analyzed following the release of results from Cohort A.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Single-Blind Placebo Run-in (Masking will be with Participant):

During the placebo run-in period, subjects will self- administer blinded placebo study medication at night prior to bedtime (@10 PM ± 90 min. each night, no sooner than 2 hrs. after dinner). Outpatient glycemic levels and adverse events will be measured using self-monitored blood glucose (SMBG) and recorded in a diary. Treatment Period (Masking will be Participant, Care Provider, Investigator, Outcomes Assessor) There are two Cohorts, A and B.

Part 1 In the first 2 weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (placebo or ORMD-0801) to be taken QHS, BID or TID.

Part 2 Subjects will remain on fixed doses of ORMD-0801 or matched placebo for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia. Treatment arms will consist of subjects receiving ORMD-0801 QHS, ORMD-0801 BID and ORMD-0801 TID versus placebo.

Primary Purpose: Treatment
Official Title: A Placebo-controlled, Multi-center, Randomized, Phase 2b Study to Evaluate the Efficacy and Safety of ORMD-0801 in Type 2 Diabetes Mellitus Patients With Inadequate Glycemic Control on Oral Therapy
Actual Study Start Date : May 29, 2018
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Insulin

Arm Intervention/treatment
Active Comparator: Cohort A: ORMD-0801 once daily - QHS
Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)
Drug: Cohort A: ORMD-0801

Part 1 In the first two weeks of active treatment (Part 1) subjects will receive double-blind therapy according to their randomized regimen (placebo or ORMD-0801) to be taken QHS, BID or TID. Subjects will undergo a step-wise dose escalation from a starting dose of 16 mg (Visit 3), to 24 mg (Visit 4), to a top dose of 32 mg (Visit 5 onward). Subjects will then enter Part 2.

Part 2:

During Part 2, subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia.

Other Name: Oral Insulin

Active Comparator: Cohort A: ORMD-0801 twice daily - BID
Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.
Drug: Cohort A: ORMD-0801

Part 1 In the first two weeks of active treatment (Part 1) subjects will receive double-blind therapy according to their randomized regimen (placebo or ORMD-0801) to be taken QHS, BID or TID. Subjects will undergo a step-wise dose escalation from a starting dose of 16 mg (Visit 3), to 24 mg (Visit 4), to a top dose of 32 mg (Visit 5 onward). Subjects will then enter Part 2.

Part 2:

During Part 2, subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia.

Other Name: Oral Insulin

Active Comparator: Cohort A: ORMD-0801 three times daily - TID
ORMD-0801 three times daily - TID: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast and lunch.
Drug: Cohort A: ORMD-0801

Part 1 In the first two weeks of active treatment (Part 1) subjects will receive double-blind therapy according to their randomized regimen (placebo or ORMD-0801) to be taken QHS, BID or TID. Subjects will undergo a step-wise dose escalation from a starting dose of 16 mg (Visit 3), to 24 mg (Visit 4), to a top dose of 32 mg (Visit 5 onward). Subjects will then enter Part 2.

Part 2:

During Part 2, subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia.

Other Name: Oral Insulin

Placebo Comparator: Cohort A: Matched Placebo Oral Capsule
Placebo matched to one of the three active comparator arms. (either QHS, BID, or TID)
Drug: Placebo oral capsule
Placebo provided QHS, BID, TID
Other Name: SBTI, disodium EDTA, fish oil, aerosil, and TWEEN 80.

Placebo Comparator: Cohort A: Excipient-Matched Placebo three times daily-TID
Excipient matched placebo in a non-randomized single-blind fashion, TID, dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast and lunch.
Drug: Placebo oral capsule
Placebo provided QHS, BID, TID
Other Name: SBTI, disodium EDTA, fish oil, aerosil, and TWEEN 80.

Active Comparator: Cohort B:ORMD-0801, 8 mg once daily - QHS:
ORMD-0801 8 mg once daily - QHS: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)
Drug: Cohort B: ORMD-0801

Part 1 In the first two weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (ORMD 0801 8 mg or 16 mg, or matched placebo) to be taken QHS or BID. Subjects will then enter Part 2 at the same dose and regimen administered in Part 1.

Part 2 Subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia.

Other Name: Oral Insulin

Active Comparator: Cohort B: ORMD-0801 8 mg twice daily - BID
ORMD-0801 8 mg twice daily - BID: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.
Drug: Cohort B: ORMD-0801

Part 1 In the first two weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (ORMD 0801 8 mg or 16 mg, or matched placebo) to be taken QHS or BID. Subjects will then enter Part 2 at the same dose and regimen administered in Part 1.

Part 2 Subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia.

Other Name: Oral Insulin

Active Comparator: Cohort B: ORMD-0801 16 mg once daily - QHS:
ORMD-0801 16 mg once daily - QHS: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)
Drug: Cohort B: ORMD-0801

Part 1 In the first two weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (ORMD 0801 8 mg or 16 mg, or matched placebo) to be taken QHS or BID. Subjects will then enter Part 2 at the same dose and regimen administered in Part 1.

Part 2 Subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia.

Other Name: Oral Insulin

Active Comparator: Cohort B: ORMD-0801 16 mg twice daily - BID
ORMD-0801 16 mg twice daily - BID: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.
Drug: Cohort B: ORMD-0801

Part 1 In the first two weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (ORMD 0801 8 mg or 16 mg, or matched placebo) to be taken QHS or BID. Subjects will then enter Part 2 at the same dose and regimen administered in Part 1.

Part 2 Subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia.

Other Name: Oral Insulin

Placebo Comparator: Excipient matched placebo once daily - QHS
Excipient matched placebo once daily - QHS: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)
Drug: Placebo oral capsule
Placebo provided QHS, BID, TID
Other Name: SBTI, disodium EDTA, fish oil, aerosil, and TWEEN 80.




Primary Outcome Measures :
  1. Mean change in HbA1C from baseline to Week 12 of the treatment period. [ Time Frame: baseline (Week 0, part 1) and Week 12 ]
    Mean change in HbA1C from baseline to Week 12 of the treatment period, measured in units of mmols/mol


Secondary Outcome Measures :
  1. Mean change from baseline over time for HbA1C [ Time Frame: Week 0 (Part 1), Week 0 (Part 2), Week 8 (Part 2) Week 10 (Part 2) ]
    Mean change from baseline over time for HbA1C (measured in mmols/mol)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.
  • Established diagnosis of T2DM for at least 6 months prior to Screening, with an HbA1C ≥ 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, SGLT-2, or TZD.
  • 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 > 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

    1. 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 <0.7 ng/mL (0.23 nmol/L).
    2. has a history of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemicalinduced, and post-organ transplant).
  • Treatment with glucosidase inhibitor, insulin secretagogues (other than sulfonylureas), glucagon-like peptide 1 (GLP-1) agonists within 3 months prior to Visit 1.
  • History of any basal, pre-mix or prandial insulin (greater than 7 days) within 6 months prior to Screening.
  • History of >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:

    1. 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.
    2. Renal dysfunction: eGFR < 30 ml/min/1.73 m2
    3. History of proliferative retinopathy or severe form of neuropathy or cardiac autonomic neuropathy (CAN)
    4. Uncontrolled or untreated severe hypertension defined as systolic blood pressure above or equal to 180 mmHg and/or diastolic blood pressure above or equal to 120 mmHg
    5. Presence of unstable angina or myocardial infarction within 6 months prior to Screening, Grade 3 or 4 congestive heart failure (CHF) according to the New York Heart Association (NYHA) criteria, valvular heart disease, cardiac arrhythmia requiring treatment, pulmonary hypertension, cardiac surgery, history/occurrence of coronary angioplasty and/or stroke or transient ischemic attack (TIA) within 6 months prior to Screening.
  • Subjects with psychiatric disorders which, per investigator judgment, may have impact on the safety of the subject or interfere with subject's participation or compliance in the study.
  • Subjects who needed (in the last 12 months) or may require systemic (oral, intravenous, intramuscular) glucocorticoid therapy for more than 2 weeks during the study period.
  • 9. Laboratory abnormalities at Screening including:

    1. C-peptide < 1.0 ng/mL
    2. Abnormal serum thyrotropin (TSH) levels below the lower limit of normal or >1.5X the upper limit of normal
    3. Elevated liver enzymes (alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase) >2X the upper limit of normal.
    4. Very high triglyceride levels (>600 mg/dL); a single repeat test is allowable.
    5. Any relevant abnormality that would interfere with the efficacy or the safety assessments during 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:

    1. History of any basal, pre-mix or prandial insulin (greater than 7 days) within 6 months prior to Screening.
    2. Administration of thyroid preparations or thyroxine (except in subjects on stable replacement therapy) within 6 weeks prior to Screening.
    3. 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.
    4. 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 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. 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. hypochlorhydria) with the potential to interfere with drug absorption.
  • At the Principal Investigator's discretion, any condition or other factors that are 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): NCT03467932


Contacts
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Contact: Kim Pope, RN, BSN +1 (210) 865-1388 kim.pope@integrium.com
Contact: Miriam Kidron, Ph.D. +972-2-566-0001 miriam@oramed.com

Locations
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United States, Michigan
AA MRC Recruiting
Flint, Michigan, United States, 48504
Contact: Fayyaz Shah    810-237-1125    fshah@aamrc.net   
Principal Investigator: Ahmed Arif, M. D.         
Sponsors and Collaborators
Oramed, Ltd.
Integrium
Investigators
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Principal Investigator: Joel M Neutel, M. D. Orange County Research Center

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Responsible Party: Oramed, Ltd.
ClinicalTrials.gov Identifier: NCT03467932     History of Changes
Other Study ID Numbers: ORA-D-015
First Posted: March 16, 2018    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019

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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 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs