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Diabetes Mellitus, Type 2Phase 2NCT04564846

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

A Phase 2 study testing ORMD-0801 in people with Diabetes Mellitus, Type 2, run by Oramed, Ltd. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
ORMD-0801
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
49 participants
Where
1 siteUnited States
Study dates
23 Nov 2020to 7 Jun 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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: estimated creatinine clearance < 30 ml/min.
  • 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 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:
  • C-peptide < 0.7 ng/mL (0.23 nmol/L).
  • Abnormal serum thyrotropin (TSH) levels below the lower limit of normal or > 1.5X the upper limit of normal.
  • Elevated liver enzymes (alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase) > 2X the upper limit of normal.
  • Very high triglyceride levels (> 600 mg/dL); a single repeat test is allowable.
  • 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:
  • History of any basal, pre-mix or prandial insulin (greater than 7 days) within 6 months prior to Screening.
  • Administration of thyroid preparations or thyroxine (except in subjects on stable replacement therapy) within 6 weeks prior to Screening.
  • 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.
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

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

    Tustin, California, 92780

Other trials in United States

About this study

Official title: 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

Read the 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.

Being tested
ORMD-0801, Placebo
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ORMD-0801Drug

    Also called Oral Insulin

    8 mg capsules of ORMD-0801 (Oral Insulin)

  • PlaceboOther

    Also called Fish Oil

    Placebo capsule (Fish Oil)

Study groups in NCT04564846
Study groupRoleWhat they receive
PlaceboPlacebo comparatorSubjects 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.
Receives: Other: Placebo
ORMD-0801Active comparatorSubjects 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.
Receives: Drug: ORMD-0801

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the Curve (AUC(0-16)) of Endogenous Glucose Production

    The endogenous glucose production in ORMD-0801 and placebo measured by the glucose with tracer attached using AUC(0-16) as the primary parameter. The intravenous infusion of [6,6-2H2]-glucose tracer is administered following administraiton of either placebo or intervention. The pharmacokinetic time points are basline (pre dose), 0.75 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, 4 hr, 5 hr, 6 hr, 7 hr, 8 hr, 9 hr, 10 hr, 11 hr, 12 hr, 13 hr, 14 hr, 15 hr, 16 hr post-dose.

    Measured: Day 28 (1 day)

Secondary outcomes (5)

  1. Mean Changes in HbA1c

    Mean Changes of HbA1c measured in percentage of glycated hemoglobin

    Measured: baseline to Day 29 of the treatment period.

  2. Area Under the Curve AUC(0-16) of Metabolite Beta-hydroxybutyrate

    AUC(0-16) measured in umol*hr/L with blood draws at baseline ( time "0", prior to drug administration), then 45 min, 90 min, 120 min, 150 min, 3-16 hours in one-hour intervals post intervention plus tracer administration via intravenous infusion of [6,6-2H2]-glucose tracer. The AUC measured is AUC(0-16) where "0-16" is 0 pre-dose, 0.75 hr. 1.5 hrs, 2 hrs. 2.5 hrs, 3 hrs, 4 hrs, 5 hrs, 6 hrs, 7 hrs, 8 hrs, 9 hrs, 10 hrs, 11 hrs, 12 hrs, 13 hrs, 14 hrs, 15 hrs, 16 hrs. post dose.

    Measured: Day 28

  3. Area Under the Curve (AUC) of Insulin

    The Area Under the Cuve (AUC) measured from baseline (prior to placebo, intervention, and tracer infusion) to sixteen hours post treatment andministration and tracer infusion administration.

    The tracer is [6,6-2H2]-glucose tracer using AUC(0-16). Pharmacokinetic time points are: Baseline (0 hr, pre-dose), then 0.75 hr, 1.5 hrs, 2 hrs, 2.5 hrs., 3 hrs., 4 hrs, 5 hrs, 6 hrs, 7hrs, 8 hrs, 9 hrs, 10 hrs, 11 hrs 12 hrs, 13 hrs, 14 hrs, 15 hrs, 16 hrs (post dose).

    Measured: Day 28 (one day)

  4. Area Under the Curve (AUC) of Free Fatty Acids (FFA)

    AUC measured from Baseline (prior to administration of placebo orintervention and to tracer infusion.

    The tracer is [6,6-2H2]-glucose tracer using AUC(0-16). Pharmacokinetic time points are: Baseline (0 hr, pre-dose), then 0.75 hr, 1.5 hrs, 2 hrs, 2.5 hrs., 3 hrs., 4 hrs, 5 hrs, 6 hrs, 7hrs, 8 hrs, 9 hrs, 10 hrs, 11 hrs 12 hrs, 13 hrs, 14 hrs, 15 hrs, 16 hrs (post dose).

    Measured: Day 28 (one day)

  5. Mean Changes Plasma Glucose Levels

    Mean changes in plasma glucose levels measured in mg/dL.

    In this outcome measure, the change from baseline of mean plasma glucose for the placebo arm is calculated as:

    Mean Plasma Glucose (Day 29, 21 subjects) - Mean Plasma Glucose (Baseline, 21 subjects). The Baseline Mean Plasma Glucose based on 21 subjects is 192.7 mg/dL. Therefore, 192.7 mg/dL - 212.3 mg/dL = -19.6 mg./dL

    Measured: baseline to Day 29 of the treatment period.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2020
  2. Study start23 Nov 2020
  3. Primary completion7 Jun 2022
  4. Study completion7 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The subject will receive either placebo or ORMD-0801
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04564846
Sponsor's protocol ID
ORA-D-018
Status last verified
Apr 2024
First submitted
21 Sep 2020
Last updated
7 May 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gastaldelli A, Baldi S, Pettiti M, Toschi E, Camastra S, Natali A, Landau BR, Ferrannini E. Influence of obesity and type 2 diabetes on gluconeogenesis and glucose output in humans: a quantitative study. Diabetes. 2000 Aug;49(8):1367-73. doi: 10.2337/diabetes.49.8.1367.

    PubMed 10923639

  • Ferrannini E, Gastaldelli A, Iozzo P. Pathophysiology of prediabetes. Med Clin North Am. 2011 Mar;95(2):327-39, vii-viii. doi: 10.1016/j.mcna.2010.11.005.

    PubMed 21281836

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ORMD-0801 in people with Diabetes Mellitus, Type 2, run by Oramed, Ltd. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Curve (AUC(0-16)) of Endogenous Glucose Production (time frame: Day 28 (1 day)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04564846, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024.

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