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

NCT03467932 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ORA-D-015
• Study Type: interventional
• Target: 373
• Locations: 1 country
• Sites: 1

Brief Summary

This is a four-way (Participant, Care Provider, Investigator, Outcomes Assessor) masked (blinded) study 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).

Conditions

T2DM (Type 2 Diabetes Mellitus)

Outcome Measures

Primary Outcomes (1)

• Change From Baseline of HbA1C (Glycated Hemoglobin)

  Least Squares Means change in HbA1C from baseline to Week 12 of the treatment period, where HbA1C is reported in units of percent. The change in HbA1c from baseline to Week 12 is expressed as a change in the value of HbA1C.

  baseline (Run-in period, Week 0, Visit 1) and Week 12 (follow-up)

Secondary Outcomes (2)

• Mean Change From Baseline Over Time for HbA1C

  Baseline (Run-In:Week 0, Visit 1) to Part 1, Visit 3, elapsed time: 3 weeks.

• Change Over Time in Hb1Ac

  Baseline (week 0, visit 1) to Week 10, part 2

Study Arms (10)

Cohort A: ORMD-0801 once daily - QHS

ACTIVE COMPARATOR

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

Drug: Cohort A: ORMD-0801

Cohort A: ORMD-0801 twice daily - BID

ACTIVE COMPARATOR

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

Drug: Cohort A: ORMD-0801

Cohort A: ORMD-0801 three times daily - TID

ACTIVE COMPARATOR

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

Cohort A: Matched Placebo Oral Capsule

PLACEBO COMPARATOR

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

Drug: Placebo oral capsule

Cohort A: Excipient-Matched Placebo three times daily-TID

PLACEBO COMPARATOR

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. This is an exploratory arm, per FDA. The results of this arm are not included in the primary analysis.

Drug: Placebo oral capsule

Cohort B:ORMD-0801, 8 mg once daily - QHS:

ACTIVE COMPARATOR

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

Drug: Cohort B: ORMD-0801

Cohort B: ORMD-0801 8 mg twice daily - BID

ACTIVE COMPARATOR

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

Cohort B: ORMD-0801 16 mg once daily - QHS:

ACTIVE COMPARATOR

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

Drug: Cohort B: ORMD-0801

Cohort B: ORMD-0801 16 mg twice daily - BID

ACTIVE COMPARATOR

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

Cohort B - Matched Placebo Oral Capsule

PLACEBO COMPARATOR

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

Drug: Placebo oral capsule

Interventions

Cohort A: ORMD-0801 DRUG

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.

Also known as: Oral Insulin

Cohort A: ORMD-0801 once daily - QHS; Cohort A: ORMD-0801 three times daily - TID; Cohort A: ORMD-0801 twice daily - BID

Placebo oral capsule DRUG

Placebo provided QHS, BID, TID

Also known as: SBTI, disodium EDTA, fish oil, aerosil, and TWEEN 80.

Cohort A: Excipient-Matched Placebo three times daily-TID; Cohort A: Matched Placebo Oral Capsule; Cohort B - Matched Placebo Oral Capsule

Cohort B: ORMD-0801 DRUG

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.

Also known as: Oral Insulin

Cohort B: ORMD-0801 16 mg once daily - QHS:; Cohort B: ORMD-0801 16 mg twice daily - BID; Cohort B: ORMD-0801 8 mg twice daily - BID; Cohort B:ORMD-0801, 8 mg once daily - QHS:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects aged 18 and older.
• Established diagnosis of T2DM for at least 6 months prior to Screening, with an HbA1C (glycated hemoglobin) ≥ 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 (DiPeptidyl Peptidase-4), SGLT-2 (Sodium-GLucose coTransporter-2), or TZD (Thiazolidinediones).
• 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 (estimated glomerular filtration rate) \> 30 ml/min/1.73 m2
• Females of childbearing potential must have a negative serum pregnancy test result at Screening.

You may not qualify if:

• Subjects with insulin-dependent diabetes
• 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).
• has a history of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, 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:
• 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.
• Renal dysfunction: eGFR \< 30 ml/min/1.73 m2
• History of proliferative retinopathy or severe form of neuropathy or cardiac autonomic neuropathy (CAN)
• 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
• 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 an impact on the safety of the subject or interfere with the 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.

Sponsors & Collaborators

• Oramed, Ltd.: lead
• Integrium: collaborator

Study Sites (1)

AA MRC

Flint, Michigan, 48504, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin; Edetic Acid; Fish Oils; Silicon Dioxide; Polysorbates

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oils; Lipids; Minerals; Inorganic Chemicals; Oxides; Oxygen Compounds; Silicon Compounds; Polyethylene Glycols; Ethylene Glycols; Glycols; Alcohols; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Miriam Kidron, Ph.D.
• Organization: Oramed Pharmaceuticals

miriam@oramed.com

+972-2-566-0100

Study Officials

• Joel M Neutel, M. D.

  Orange County Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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: Participant, Care Provider, Investigator, Outcomes Assessor) There are 2 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 (bedtime), BID (2 X / day) 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, BID, and TID versus placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2018
• First Posted: March 16, 2018
• Study Start: May 29, 2018
• Primary Completion: October 21, 2019
• Study Completion: February 18, 2020
• Last Updated: November 8, 2022
• Results First Posted: November 8, 2022

Record last verified: 2022-11

Locations

US (1)