Study NCT03467932
A Study to Evaluate the Efficacy and Safety of ORMD-0801 (Oral Insulin) in Patients With Type 2 Diabetes Mellitus
Submitted Date:  October 14, 2021 (v12)
Quality Control Review Has Not Concluded

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This submission includes brief standardized QC review comments added by the National Library of Medicine (NLM). These comments indicate the location of apparent errors, deficiencies, or inconsistencies. For more information, see the Final Rule (42 CFR Part 11) Information page.


Open or close this module Study Identification
Unique Protocol ID: ORA-D-015
Brief Title: A Study to Evaluate the Efficacy and Safety of ORMD-0801 (Oral Insulin) in Patients With Type 2 Diabetes Mellitus
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
Secondary IDs:
Open or close this module Study Status
Record Verification: October 2021
Overall Status: Completed
Study Start: May 29, 2018
Primary Completion: October 21, 2019 [Actual]
Study Completion: February 18, 2020 [Actual]
First Submitted: March 1, 2018
First Submitted that
Met QC Criteria:
March 10, 2018
First Posted: March 16, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: November 15, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Oramed, Ltd.
Responsible Party: Sponsor
Collaborators: Integrium
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
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).
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.

Open or close this module Conditions
Conditions: T2DM (Type 2 Diabetes Mellitus)
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 10
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 419 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Oral Insulin
Placebo Comparator: Cohort B - Matched Placebo Oral Capsule
Cohort B - Matched Placebo Oral Capsule: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)
Drug: Placebo oral capsule
Placebo provided QHS, BID, TID
Other Names:
  • SBTI, disodium EDTA, fish oil, aerosil, and TWEEN 80.
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Change From Baseline of HbA1C
[ Time Frame: baseline (Week 0, part 1) and Week 12 ]

Least Squares Means change in HbA1C from baseline to Week 12 of the treatment period, measured in units of percent
Secondary Outcome Measures:
1. Mean Change From Baseline Over Time for HbA1C
[ Time Frame: Baseline to Week 0 ]

Mean change from baseline to Week(0) Part I for HbA1C (measured in mmols/mol)

Quality Control Review Comment provided by the National Library of Medicine:

  1. There does not appear to be sufficient information to understand the Time Frame.
2. Change Over Time in Hb1Ac
[ Time Frame: Baseline to Week 10 ]

Change of Hb1Ac from Baseline to Week 10, measured in mmol/mol
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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.
Open or close this module Contacts/Locations
Study Officials: Joel M Neutel, M. D.
Principal Investigator
Orange County Research Center
Locations: United States, Michigan
AA MRC
Flint, Michigan, United States, 48504
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol and Statistical Analysis Plan
Document Date: April 4, 2019
Uploaded: 08/19/2021 22:31
File Name: Prot_SAP_000.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details
Pre-assignment Details
 
Arm/Group Title Cohort A: ORMD-0801 Once Daily - QHS Cohort A: ORMD-0801 Twice Daily - BID Cohort A: ORMD-0801 Three Times Daily - TID Cohort A: Matched Placebo Oral Capsule Cohort A: Excipient-Matched Placebo Three Times Daily-TID Cohort B:ORMD-0801, 8 mg Once Daily - QHS: Cohort B: ORMD-0801 8 mg Twice Daily - BID Cohort B: ORMD-0801 16 mg Once Daily - QHS: Cohort B: ORMD-0801 16 mg Twice Daily - BID Cohort B - Matched Placebo Oral Capsule
Arm/Group Description

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)

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.

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.

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.

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.

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.

Placebo matched to one of the three active comparator arms. (either QHS, BID, or TID)

Placebo oral capsule: Placebo provided QHS, BID, 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.

Placebo oral capsule: Placebo provided QHS, BID, TID

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

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.

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.

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.

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

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.

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.

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.

Cohort B - Matched Placebo Oral Capsule: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)

Placebo oral capsule: Placebo provided QHS, BID, TID

Period Title: Overall Study
Started 69 68 69 66 20 15 17 18 15 16
Completed 62 58 58 56 19 13 15 16 11 14
Not Completed 7 10 11 10 1 2 2 2 4 2
Open or close this module Baseline Characteristics
Arm/Group TitleCombined PlaceboCohort A: ORMD-0801 Once Daily - QDCohort A: ORMD-0801 Twice Daily - BIDCohort A: ORMD-0801 Three Times Daily - TIDCohort B:ORMD-0801, 8 mg Once Daily - QDCohort B: ORMD-0801 8 mg Twice Daily - BIDCohort B: ORMD-0801 16 mg Once Daily - QDCohort B: ORMD-0801 16 mg Twice Daily - BIDTotal
Arm/Group Description

Placebo matched to one of the three active comparator arms. (either QHS, BID, or TID)

Placebo oral capsule: Placebo provided QHS, BID, TID

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)

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.

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.

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.

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.

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.

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

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.

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.

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.

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

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.

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 82 69 68 69 15 17 18 15 353
Baseline Analysis Population Description [Not Specified]

Quality Control Review Comment provided by the National Library of Medicine:

  1. The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided.
Age, Continuous
Mean (Standard Deviation)
Unit of measure: years
Number Analyzed82 Participants69 Participants68 Participants69 Participants15 Participants17 Participants18 Participants15 Participants353 Participants
55.92(9.914)56.72(10.766)55.68(10.569)55.22(11.663)53.66(8.22)56.87(9.132)54.98(11.229)54.98(11.785)55.73(10.544)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed82 Participants69 Participants68 Participants69 Participants15 Participants17 Participants18 Participants15 Participants353 Participants
Female
33
40.24%
27
39.13%
23
33.82%
29
42.03%
5
33.33%
7
41.18%
7
38.89%
4
26.67%
135
38.24%
Male
49
59.76%
42
60.87%
45
66.18%
40
57.97%
10
66.67%
10
58.82%
11
61.11%
11
73.33%
218
61.76%
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed82 Participants69 Participants68 Participants69 Participants15 Participants17 Participants18 Participants15 Participants353 Participants
Hispanic or Latino
48
58.54%
36
52.17%
37
54.41%
36
52.17%
9
60%
8
47.06%
9
50%
8
53.33%
191
54.11%
Not Hispanic or Latino
33
40.24%
32
46.38%
29
42.65%
33
47.83%
6
40%
6
35.29%
9
50%
6
40%
154
43.63%
Unknown or Not Reported
1
1.22%
1
1.45%
2
2.94%
0
0%
0
0%
3
17.65%
0
0%
1
6.67%
8
2.27%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed82 Participants69 Participants68 Participants69 Participants15 Participants17 Participants18 Participants15 Participants353 Participants
American Indian or Alaska Native
0
0%
0
0%
0
0%
1
1.45%
0
0%
0
0%
0
0%
0
0%
1
0.28%
Asian
0
0%
0
0%
2
2.94%
1
1.45%
0
0%
0
0%
1
5.56%
2
13.33%
6
1.7%
Native Hawaiian or Other Pacific Islander
1
1.22%
1
1.45%
1
1.47%
1
1.45%
0
0%
0
0%
0
0%
0
0%
4
1.13%
Black or African American
11
13.41%
7
10.14%
8
11.76%
8
11.59%
3
20%
4
23.53%
1
5.56%
1
6.67%
43
12.18%
White
69
84.15%
59
85.51%
57
83.82%
58
84.06%
12
80%
11
64.71%
16
88.89%
11
73.33%
293
83%
More than one race
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
1
1.22%
2
2.9%
0
0%
0
0%
0
0%
2
11.76%
0
0%
1
6.67%
6
1.7%
BMI
Mean (Standard Deviation)
Unit of measure: Kg/M^2
Number Analyzed82 Participants69 Participants68 Participants69 Participants15 Participants17 Participants18 Participants15 Participants353 Participants
31.137(4.7750)31.721(4.9409)30.447(4.7710)31.191(4.0045)31.759(4.4393)31.005(5.0333)31.881(6.0514)30.776(5.4530)31.171(4.7203)
HbA1c
Mean (Standard Deviation)
Unit of measure: percent
Number Analyzed82 Participants69 Participants68 Participants69 Participants15 Participants17 Participants18 Participants15 Participants353 Participants
9.46(1.434)8.96(1.281)9.36(1.656)9.64(1.578)9.83(1.759)8.46(1.104)8.96(1.420)9.18(1.687)9.31(1.512)
Diabetes Medications
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed82 Participants69 Participants68 Participants69 Participants15 Participants17 Participants18 Participants15 Participants353 Participants
Metformin Alone
22
26.83%
20
28.99%
20
29.41%
12
17.39%
6
40%
5
29.41%
7
38.89%
5
33.33%
97
27.48%
Metformin, No Sulfonylureas, but At Least 1 Other Medication
13
15.85%
10
14.49%
8
11.76%
12
17.39%
1
6.67%
0
0%
1
5.56%
2
13.33%
47
13.31%
Metformin with Sulfonylureas Only
33
40.24%
30
43.48%
26
38.24%
33
47.83%
7
46.67%
7
41.18%
8
44.44%
3
20%
147
41.64%
Metformin with Sulfonylureas and Other Medication(s)
10
12.2%
5
7.25%
8
11.76%
6
8.7%
0
0%
1
5.88%
1
5.56%
3
20%
34
9.63%
Not on Metformin, But On 1 Other Medication
4
4.88%
4
5.8%
3
4.41%
4
5.8%
1
6.67%
2
11.76%
0
0%
1
6.67%
19
5.38%
Not on Metformin, But On At Least 2 Other Medications
0
0%
0
0%
3
4.41%
2
2.9%
0
0%
2
11.76%
1
5.56%
1
6.67%
9
2.55%
Open or close this module Outcome Measures
1. Primary Outcome:
Title Change From Baseline of HbA1C
Description Least Squares Means change in HbA1C from baseline to Week 12 of the treatment period, measured in units of percent
Time Frame baseline (Week 0, part 1) and Week 12
Outcome Measure Data
Analysis Population Description
Intent-to-treat excluding patients from sites 13 and 20 per agreement with FDA.
 
Arm/Group TitleCombined Placebo Oral CapsuleCohort A: ORMD-0801 Once Daily - QHSCohort A: ORMD-0801 Twice Daily - BIDCohort A: ORMD-0801 Three Times Daily - TIDCohort B:ORMD-0801, 8 mg Once Daily - QHS:Cohort B: ORMD-0801 8 mg Twice Daily - BIDCohort B: ORMD-0801 16 mg Once Daily - QHS:Cohort B: ORMD-0801 16 mg Twice Daily - BID
Arm/Group Description

Placebo matched to one of the three active comparator arms. (either QHS, BID, or TID)

Placebo oral capsule: Placebo provided QHS, BID, TID

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)

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.

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.

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.

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.

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.

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

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.

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.

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.

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

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.

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.

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.

Overall Number of Participants Analyzed53 59 54 52 13 12 13 10
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent
-0.13(-0.86 to 0.59) -0.60(-1.37 to 0.16) -0.59(-1.32 to 0.14) -0.51(-1.27 to 0.25) -0.95(-1.87 to -0.03) -0.95(-1.84 to -0.07) 0.12(-0.80 to 1.04) -0.50(-1.47 to 0.48)

Quality Control Review Comment provided by the National Library of Medicine:

  1. The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided.
2. Secondary Outcome:
Title Mean Change From Baseline Over Time for HbA1C
Description Mean change from baseline to Week(0) Part I for HbA1C (measured in mmols/mol)
Time Frame Baseline to Week 0

Quality Control Review Comment provided by the National Library of Medicine:

  1. There does not appear to be sufficient information to understand the Time Frame.
Outcome Measure Data
Analysis Population Description
Intend-to-Treat, excluding patients from sites 13 and 20, per agreement with FDA.
 
Arm/Group TitleCombined PlaceboCohort A: ORMD-0801 Once Daily - QHSCohort A: ORMD-0801 Twice Daily - BIDCohort A: ORMD-0801 Three Times Daily - TIDCohort B:ORMD-0801, 8 mg Once Daily - QHS:Cohort B: ORMD-0801 8 mg Twice Daily - BIDCohort B: ORMD-0801 16 mg Once Daily - QHS:Cohort B: ORMD-0801 16 mg Twice Daily - BID
Arm/Group Description

Placebo matched to one of the three active comparator arms. (either QHS, BID, or TID)

Placebo oral capsule: Placebo provided QHS, BID, TID

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)

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.

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.

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.

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.

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.

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

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.

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.

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.

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

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.

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.

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.

Overall Number of Participants Analyzed61 62 62 58 14 13 14 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/mol
-2.12(-4.40 to 0.16) -2.56(-4.94 to -0.19) -1.95(-4.21 to 0.30) -2.91(-5.25 to -0.57) -3.26(-6.13 to -0.39) -5.51(-8.30 to -2.73) -2.06(-4.94 to 0.82) -1.87(-4.72 to 0.98)

Quality Control Review Comment provided by the National Library of Medicine:

  1. The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided.
3. Secondary Outcome:
Title Change Over Time in Hb1Ac
Description Change of Hb1Ac from Baseline to Week 10, measured in mmol/mol
Time Frame Baseline to Week 10
Outcome Measure Data
Analysis Population Description
Intent-to-Treat, excluding sites 13 and 20, per agreement with FDA.
 
Arm/Group TitleCombined PlaceboCohort A: ORMD-0801 Once Daily - QDCohort A: ORMD-0801 Twice Daily - BIDCohort A: ORMD-0801 Three Times Daily - TIDCohort B:ORMD-0801, 8 mg Once Daily - QDCohort B: ORMD-0801 8 mg Twice Daily - BIDCohort B: ORMD-0801 16 mg Once Daily - QDCohort B: ORMD-0801 16 mg Twice Daily - BID
Arm/Group Description

Placebo matched to one of the three active comparator arms. (either QHS, BID, or TID)

Placebo oral capsule: Placebo provided QHS, BID, TID

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)

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.

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.

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.

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.

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.

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

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.

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.

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.

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

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.

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.

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.

Overall Number of Participants Analyzed53 58 54 50 13 12 13 11
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/mol
-1.27(-8.88 to 6.35) -5.95(-14.05 to 2.16) -4.95(-12.62 to 2.73) -6.16(-14.22 to 1.90) -10.34(-20.01 to -0.68) -10.71(-20.02 to -1.40) -0.25(-9.94 to 9.44) -4.66(-14.61 to 5.28)

Quality Control Review Comment provided by the National Library of Medicine:

  1. The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided.
Open or close this module Adverse Events
 
Time Frame 1 year, 2 months
Adverse Event Reporting Description [Not specified]
 
Arm/Group Title Combined Placebo Cohort A: ORMD-0801 Once Daily - QD Cohort A: ORMD-0801 Twice Daily - BID Cohort A: ORMD-0801 Three Times Daily - TID Cohort B:ORMD-0801, 8 mg Once Daily - QD Cohort B: ORMD-0801 8 mg Twice Daily - BID Cohort B: ORMD-0801 16 mg Once Daily - QD Cohort B: ORMD-0801 16 mg Twice Daily - BID
Arm/Group Description

Placebo matched to one of the three active comparator arms. (either QHS, BID, or TID)

Placebo oral capsule: Placebo provided QHS, BID, TID

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)

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.

Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.

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.

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.

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.

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

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.

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.

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.

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

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.

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.

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.

Quality Control Review Comment provided by the National Library of Medicine:

  1. The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided.
All-Cause Mortality
  Combined PlaceboCohort A: ORMD-0801 Once Daily - QDCohort A: ORMD-0801 Twice Daily - BIDCohort A: ORMD-0801 Three Times Daily - TIDCohort B:ORMD-0801, 8 mg Once Daily - QDCohort B: ORMD-0801 8 mg Twice Daily - BIDCohort B: ORMD-0801 16 mg Once Daily - QDCohort B: ORMD-0801 16 mg Twice Daily - BID
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 0 / 82 (0%)0 / 68 (0%)0 / 69 (0%)0 / 68 (0%)0 / 15 (0%)0 / 17 (0%)0 / 17 (0%)0 / 15 (0%)
Serious Adverse Events
  Combined PlaceboCohort A: ORMD-0801 Once Daily - QDCohort A: ORMD-0801 Twice Daily - BIDCohort A: ORMD-0801 Three Times Daily - TIDCohort B:ORMD-0801, 8 mg Once Daily - QDCohort B: ORMD-0801 8 mg Twice Daily - BIDCohort B: ORMD-0801 16 mg Once Daily - QDCohort B: ORMD-0801 16 mg Twice Daily - BID
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 0 / 82 (0%)5 / 69 (7.25%)0 / 68 (0%)3 / 69 (4.35%)0 / 15 (0%)0 / 17 (0%)0 / 18 (0%)1 / 15 (6.67%)
Cardiac disorders
Acute Myocardial Infarction † A 0 / 82 (0%)00 / 69 (0%)00 / 68 (0%)01 / 69 (1.45%)10 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Angina Pectoris † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Atrial Fibrillation † A 0 / 82 (0%)02 / 69 (2.9%)20 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Coronary Artery Disease † A 0 / 82 (0%)00 / 69 (0%)00 / 68 (0%)01 / 69 (1.45%)10 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Supraventricular Tachycardia † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
General disorders
Chest Pain † A 0 / 82 (0%)00 / 69 (0%)00 / 68 (0%)01 / 69 (1.45%)10 / 15 (0%)00 / 17 (0%)00 / 18 (0%)01 / 15 (6.67%)1
Infections and infestations
Sepsis † A 0 / 82 (0%)00 / 69 (0%)00 / 68 (0%)01 / 69 (1.45%)10 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Urosepsis † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Renal and urinary disorders
Acute Kidney Injury † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Respiratory, thoracic and mediastinal disorders
Asthma † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Chronic Obstructive Pulmonary Disease † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA (10.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
  Combined PlaceboCohort A: ORMD-0801 Once Daily - QDCohort A: ORMD-0801 Twice Daily - BIDCohort A: ORMD-0801 Three Times Daily - TIDCohort B:ORMD-0801, 8 mg Once Daily - QDCohort B: ORMD-0801 8 mg Twice Daily - BIDCohort B: ORMD-0801 16 mg Once Daily - QDCohort B: ORMD-0801 16 mg Twice Daily - BID
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 11 / 82 (13.41%)19 / 69 (27.54%)6 / 68 (8.82%)10 / 69 (14.49%)5 / 15 (33.33%)2 / 17 (11.76%)1 / 18 (5.56%)2 / 15 (13.33%)
Blood and lymphatic system disorders
Anemia † A 0 / 82 (0%)03 / 69 (4.35%)31 / 68 (1.47%)10 / 69 (0%)00 / 15 (0%)01 / 17 (5.88%)11 / 18 (5.56%)10 / 15 (0%)0
Cardiac disorders
Angina Pectoris † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Atrial Fibrillation † A 0 / 82 (0%)03 / 69 (4.35%)31 / 68 (1.47%)10 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Atrioventricular Block First Degree † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Palpitations † A 1 / 82 (1.22%)10 / 69 (0%)00 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Supraventricular Tachycardia † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Gastrointestinal disorders
Abdominal discomfort † A 1 / 82 (1.22%)10 / 69 (0%)00 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Abdominal pain Upper † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Constipation † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)01 / 15 (6.67%)10 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Cystitis † A 1 / 82 (1.22%)10 / 69 (0%)00 / 68 (0%)00 / 69 (0%)01 / 15 (6.67%)11 / 17 (5.88%)10 / 18 (0%)00 / 15 (0%)0
Diarrhoea † A 3 / 82 (3.66%)32 / 69 (2.9%)23 / 68 (4.41%)38 / 69 (11.59%)81 / 15 (6.67%)10 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Large Intestine Polyp † A 1 / 82 (1.22%)10 / 69 (0%)00 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Nausea † A 1 / 82 (1.22%)12 / 69 (2.9%)20 / 68 (0%)01 / 69 (1.45%)11 / 15 (6.67%)10 / 17 (0%)00 / 18 (0%)01 / 15 (6.67%)1
Pancreatic Cyst † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Immune system disorders
Hypersensitivity † A 0 / 82 (0%)00 / 69 (0%)00 / 68 (0%)00 / 69 (0%)01 / 15 (6.67%)10 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Seasonal Allergy † A 1 / 82 (1.22%)11 / 69 (1.45%)10 / 68 (0%)01 / 69 (1.45%)10 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Infections and infestations
Acute Sinusitis † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Adenoviral upper respiratory infection † A 1 / 82 (1.22%)10 / 69 (0%)00 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Body Tinea † A 0 / 82 (0%)01 / 69 (1.45%)10 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Bronchitis † A 0 / 82 (0%)01 / 69 (1.45%)11 / 68 (1.47%)10 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Cellulitis † A 1 / 82 (1.22%)10 / 69 (0%)00 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Conjunctivitis † A 1 / 82 (1.22%)10 / 69 (0%)00 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Diverticulitis † A 0 / 82 (0%)00 / 69 (0%)00 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)01 / 15 (6.67%)1
Gastroenteritis Viral † A 1 / 82 (1.22%)10 / 69 (0%)00 / 68 (0%)00 / 69 (0%)00 / 15 (0%)00 / 17 (0%)00 / 18 (0%)00 / 15 (0%)0
Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA (10.0)
Open or close this module Limitations and Caveats
[Not specified]
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact:
Name/Official Title:
Miriam Kidron, Ph.D.
Organization:
Oramed Pharmaceuticals
Phone:
+972-2-566-0100
Email:
miriam@oramed.com

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