A Study of Single and Multiple Doses of Oral Insulin or Placebo in Subjects With Type 2 Diabetes Mellitus

NCT02954601 | Completed Phase 2 Results DMC

• 1 other identifier: ORA-D-012
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This is a four-way crossover (non-parallel) study with each subject receiving three of the four arms. The study will enroll approximately 30 adult subjects with T2DM from age 20 to 75 inclusive. Following a 7-10 day Screening period, eligible subjects will enter a 3-day single-blind placebo run-in. On Day 4, each subject will be randomized to a treatment sequence that will include three treatment assignments for each of three treatment Periods according to the randomization scheme.

Conditions

Type 2 Diabetes Mellitus

Keywords

Oral Insulin; DM T2 (Diabetes Mellitus Type 2)

Outcome Measures

Primary Outcomes (1)

• Change in Glucose Levels Between Pre-treatment and End of Treatment as Measured by 24-hour Continuous Glucose Monitoring (CGM)

  Measure the change in Glucose (mg/dL) by 24 hour CGM between Day3 and Day8 (Change in mg/dL between run-in and Day 5 of Active treatment)

  Day 3 (run-in) and Day 8 (Day 5 of Active treatment)

Secondary Outcomes (3)

• Calculate the C-peptide Ratio for Single and Multiple Doses of ORMD-0801 vs Placebo.

  Day 3 and Day 8

• The Number Hypoglycemic Events for Single and Multiple Doses of ORMD-0801 vs Placebo

  Day 3 through Day 8 of treatment

• Calculate the Difference Between Values of Pre-treatment and End-of-treatment Mean Daytime CGM Glucose

  Day 3 and Day 8 (two timepoints)

Study Arms (4)

Placebo

ACTIVE COMPARATOR

Placebo (fish oil)

Other: Placebo

Dose1

ACTIVE COMPARATOR

Dose 1 ORMD-0801 (qd)

Drug: ORMD-0801 (qd)

Dose2

ACTIVE COMPARATOR

Dose 2 ORMD-0801 (bid)

Drug: ORMD-0801 (bid)

Dose 3

ACTIVE COMPARATOR

Dose 3 ORMD-0801 (tid)

Drug: ORMD-0801 (tid)

Interventions

ORMD-0801 (qd) DRUG

Dose 1 = ORMD-0801 (qd)

Also known as: Oral Insulin

Dose1

ORMD-0801 (bid) DRUG

Dose 2 = ORMD-0801 (bid)

Also known as: Oral Insulin

Dose2

ORMD-0801 (tid) DRUG

Dose 3 = ORMD-0801 (tid)

Also known as: Oral Insulin

Dose 3

Placebo OTHER

fish oil placebo

Also known as: fish oil

Placebo

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, age 20 to 75 years, inclusive with type 2 diabetes mellitus.
• At Visit 2/Period 1/Day 1, subjects will have been treated for their diabetes by metformin (≥1000 mg/day; any type and regimen), metformin and a DPP-4 inhibitor ( Dipeptidyl-Peptidase)-4), metformin and an SGLT-2 (Sodium-glucose co-transporter 2) inhibitor, metformin and TZD (Thiazolidinediones), or metformin and sulfonylurea. Subjects will have been on a stable regimen of metformin (defined as the same metformin dose and type) and other treatments for at least 8 weeks prior to Visit 2/Period 1/Day 1.
• Body Mass Index (BMI) between 25 and 40 kg/m2, inclusive, at Screening.
• Hemoglobin A1c (HbA1c) between ≥7.5 and ≤10.5% at Screening.
• Fasting serum glucose greater than or equal to 126 mg/dL at Screening.
• Females of childbearing potential must have a negative serum pregnancy test result at Screening and a negative urine pregnancy test at Visit 2/Day 1 for all study Periods.
• Females who are not of childbearing potential are defined as:
• i. Postmenopausal (defined as at least 12 months with no menses in women ≥45 years of age) ii. Has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR iii. Has a congenital or acquired condition that prevents childbearing.
• Females of childbearing potential agree to avoid becoming pregnant while receiving study treatment and for 14 days after the last dose of study treatment by complying with one of the following:
• i. practice abstinence† from heterosexual activity OR ii. Use (or have her partner use) acceptable contraception during heterosexual activity.

You may not qualify if:

• Usage of anti-diabetic agents other than metformin, sulfonylurea, SGLT-2 inhibitors, TZD, or DPP-4 inhibitors within 6 weeks prior to Visit 2/Period 1/Day 1.
• Presence of any clinically significant endocrine disease according to the Investigator (euthyroid subjects on replacement therapy will be included if the dosage of thyroxine is stable for at least six weeks prior to Screening).
• Clinical diagnosis of type 1 diabetes.
• Fasting serum glucose \>300 mg/dL at Screening; a single repeat test is allowable.
• Evidence of unawareness of hypoglycemia, a documented plasma glucose ≤50 mg/dL in the absence of symptoms of hypoglycemia at Screening.
• Presence of any clinically significant condition (in the opinion of the Investigator) that might interfere with the evaluation of study medication, such as significant renal, hepatic, gastrointestinal (GI), cardiovascular (CV), immune disease, blood dyscrasias or any disorders causing hemolysis or unstable red blood cells, or clinically important hematological disorders (i.e. aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) at Screening.
• Presence or history of cancer within the past 5 years of Screening, with the exception of adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer.
• A subject with a history of malignancy \>5 years prior to Screening should have no evidence of residual or recurrent disease.
• A subject with a history of melanoma, leukemia, lymphoma, or renal carcinoma is excluded.
• Laboratory abnormalities at Screening including:
• C-peptide \< 1.0 ng/mL;
• Positive pregnancy test in females of childbearing potential (at Screening and Visit 2/Periods 1-3/Day 1);
• Abnormal serum thyrotropin (TSH) levels below the lower limit of normal or \>1.5X (1.5 times) 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.

Sponsors & Collaborators

• Oramed, Ltd.: lead
• Integrium: collaborator

Study Sites (1)

Orange County Research Center

Tustin, California, 92780, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ORMD-0801; Insulin; BID protein, human; 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

miriam@oramed.com

+972-2-566-0001

Study Officials

• Joel M Neutel, M. D.

  Orange County Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2016
• First Posted: November 3, 2016
• Study Start: October 1, 2016
• Primary Completion: February 24, 2017
• Study Completion: March 15, 2017
• Last Updated: July 12, 2018
• Results First Posted: July 12, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)