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

NCT04564846 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ORA-D-018
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (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.

  Day 28 (1 day)

Secondary Outcomes (5)

• Mean Changes in HbA1c

  baseline to Day 29 of the treatment period.

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

  Day 28

• Area Under the Curve (AUC) of Insulin

  Day 28 (one day)

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

  Day 28 (one day)

• Mean Changes Plasma Glucose Levels

  baseline to Day 29 of the treatment period.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

ORMD-0801

ACTIVE COMPARATOR

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.

Drug: ORMD-0801

Interventions

ORMD-0801 DRUG

8 mg capsules of ORMD-0801 (Oral Insulin)

Also known as: Oral Insulin

ORMD-0801

Placebo OTHER

Placebo capsule (Fish Oil)

Also known as: Fish Oil

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

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: 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.

Sponsors & Collaborators

• Oramed, Ltd.: lead

Study Sites (1)

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

Tustin, California, 92780, United States

Location

Related Publications (2)

• 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.

  PMID: 10923639 BACKGROUND

• 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.

  PMID: 21281836 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ORMD-0801; Insulin; Fish Oils

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; Oils; Lipids

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Oramed, Ltd.

miriam@oramed.com

+97225660001

Study Officials

• Joel M Neutel, M. D.

  Orange County Research Center (OCRC)

  PRINCIPAL INVESTIGATOR

• Ele Ferrannini, M. D.

  CNR Institute of Clinical Physiology

  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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participant, Care Provider, and Investigator will be masked to the intervention (ORMD-0801 or placebo)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The subject will receive either placebo or ORMD-0801

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: September 25, 2020
• Study Start: November 23, 2020
• Primary Completion: June 7, 2022
• Study Completion: June 7, 2022
• Last Updated: May 7, 2024
• Results First Posted: May 7, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)