A Study to Evaluate the Effect of ORMD-0801 in Patients With Type 2 Diabetes Mellitus

September 13, 2022 updated by: Oramed, Ltd.

A Randomized, Double Blind, Phase 2b Study to Evaluate the Effect of ORMD-0801 Compared to Placebo on Endogenous Glucose Production in Patients With Type 2 Diabetes Mellitus

This study is designed to explore the efficacy of ORMD-0801 compared to placebo on endogenous glucose production in subjects with type 2 diabetes (T2DM). Subjects will undergo an initial Screening Visit (Visit 0) to establish their eligibility to participate in the study. At Visit 1 (2 weeks after the Screening Visit), qualifying subjects will be randomized to either ORMD-0801 (8 mg) or matching placebo, study medication will be dispensed and subjects will dose, twice a day, once in the morning prior to breakfast and once at night prior to bedtime

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

This study is designed to explore the efficacy of ORMD-0801 compared to placebo on endogenous glucose production in subjects with type 2 diabetes (T2DM). Subjects will undergo an initial Screening Visit (Visit 0) to establish their eligibility to participate in the study. At Visit 1 (2 weeks after the Screening Visit), qualifying subjects will be randomized to either ORMD-0801 (8 mg) or matching placebo, study medication will be dispensed and subjects will dose, twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Doses will occur at 45 minutes (± 15 minutes) before breakfast and no later than 10 AM each morning, and at 8 PM (± 120 minutes) each night, and no sooner than 1 hour after dinner. Subjects will return to the clinic, 2 weeks later, for Visit 2. At this visit, subject compliance will be assessed, medication will be dispensed, a blood sample will be collected to measure HbA1c and subjects will be questioned for any adverse events. Subjects will be scheduled to return to the clinic in 2 weeks for morning admission (8 AM ± 120 minutes) to the PK unit (Visit 3). Subjects will be provided with standardized meals and the morning dose in-clinic. A light standardized dinner meal will be provided at 6 PM ± 30 minutes. At approximately 8 PM (± 60 minutes, and no sooner than 1 hour after dinner), subjects will be dosed with their study medication and will be started on a 16-hour infusion of [6,6-2H2]-glucose tracer.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Tustin, California, United States, 92780
        • Orange County Research Center (OCRC) 14351 Myford Rd., Suite B, Tustin, CA 92780

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female subjects aged, 18 - 70 years.
  • Established diagnosis of T2DM for at least 6 months prior to Screening, with HbA1c ≥ 7.5%. and ≤ 11%.
  • Stable dose of metformin (at least 1500 mg or maximal tolerated dose) 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 35 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 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:

    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: estimated creatinine clearance < 30 ml/min.
    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.
  • Laboratory abnormalities at Screening including:

    1. C-peptide < 0.7 ng/mL (0.23 nmol/L).
    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.
  • Subject is smoking more than 10 cigarettes per day.
  • 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 factor that is deemed unsuitable for subject enrollment into the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime.
Placebo capsule (Fish Oil)
Other Names:
  • Fish Oil
ACTIVE_COMPARATOR: ORMD-0801
Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime.
8 mg capsules of ORMD-0801 (Oral Insulin)
Other Names:
  • Oral Insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in Area Under the Curve (AUC(0-16)) of endogenous glucose production between placebo and ORMD-0801
Time Frame: Day 29 (1 day)
The difference in endogenous glucose production between active and placebo as measured by the glucose with tracer attached using AUC(0-16) as the primary parameter.
Day 29 (1 day)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean changes in HbA1c
Time Frame: baseline to Day 29 of the treatment period.
Mean Changes of HbA1c measured in percent
baseline to Day 29 of the treatment period.
Mean changes plasma glucose levels
Time Frame: baseline to Day 29 of the treatment period.
Mean changes in plasma glucose levels measured in mg/dL
baseline to Day 29 of the treatment period.
Mean changes in ketones from baseline to Day 29 of the treatment period.
Time Frame: baseline to Day 29 of the treatment period.
Mean changes in ketones measured in percent
baseline to Day 29 of the treatment period.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Joel M Neutel, M. D., Orange County Research Center (OCRC)
  • Principal Investigator: Ele Ferrannini, M. D., CNR Institute of Clinical Physiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 23, 2020

Primary Completion (ACTUAL)

June 7, 2022

Study Completion (ACTUAL)

June 7, 2022

Study Registration Dates

First Submitted

September 21, 2020

First Submitted That Met QC Criteria

September 21, 2020

First Posted (ACTUAL)

September 25, 2020

Study Record Updates

Last Update Posted (ACTUAL)

September 14, 2022

Last Update Submitted That Met QC Criteria

September 13, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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