A Study to Compare ORMD-0801 Once Daily to ORMD-0801 Three Times Daily in Subjects With Type 1 Diabetes

NCT04150107 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ORA-D-017
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a Phase 2 randomized, crossover study comparing ORMD-0801 given QD versus TID in subjects with T1D. Subjects with T1D will have a screening visit (Visit 1) during which they will be required to review and sign the informed consent form. Medical history and demographics will be collected. Vital signs will be measured, physical exam will be performed, and blood and urine samples will be collected for hematology/chemistry/urinalysis Placebo capsules will be given QD at bedtime during placebo run-in period 10 days prior to randomization.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (3)

• Average Exogenous Basal Insulin Compared to Baseline (Placebo)

  The least squares means difference of basal exogenous insulin between treatment A and placebo and treatment B and placebo, utilized over the final ten (10) days of each treatment period

  Combined Final ten days of each treatment period. Period1 (days -8 to 1)Period 2 (days 19 to 28) ,and Period 3 (days 47 to 56)

• Average Exogenous Bolus Insulin Compared to Baseline (Placebo)

  The amount of exogenous bolus insulin utilized over the final ten (10) days of each treatment period measured in mg/dL

  Combined Final ten days of treatment per treatment period (Days -8 to 1, Days 19 to 28, and Days 47 to 56)

• Average Exogenous Total Insulin Compared to Baseline

  The Least Squares Mean Difeerence ( (mg/dL) of total exogenous insulin (the sum of basal + bolus exogenous insulin) over the final ten (10) days of treatment.

  Combined Final ten days of treatment , day -8 to 1 (Period 1) Days 19 to 28 (Period 2), Days 47 to 56 (Period 3)

Secondary Outcomes (3)

• Daytime Average Mean Glucose Compared to Baseline

  Combined Study days -8 to 1 (Period 1) Days 19 to 28 (Period 2), and days 47 to 56 (Period 3)

• Daytime Glucose Coefficient of Variation Compared to Baseline

  Study Days -8 to 1 (Period 1), Days 19-28 (Period 2), and Days 47-56 (Period 3)

• Daytime Low Blood Glucose Index (LBGI) Compared to Baseline

  Combined Study Days -8 to 1 (Period 1), Days 19-28 (Period 2), and Days 47-56 (Period 3)

Study Arms (2)

Placebo then Treatment A then Treatment B

EXPERIMENTAL

Treatment administered in the following order: 1. Period 1: Placebo (Fish Oil Capsule) 2. Period 2: Treatment A: 24 mg ORMD-0801;(16 mg + 8 mg capsules) Once Daily (QD) at Bedtime 3. Period 3:Treatment B: 8 mg ORMD-0801; one 8 mg capsule three times a day (TID) 45-90 minutes before meals

Drug: ORMD-0801 Treatment A; Drug: ORMD-0801 Treatment B; Other: Placebo

Placebo then Treatment B then Treatment A

EXPERIMENTAL

Treatment administered in the following order: 1. Period 1: Placebo (Fish Oil Capsule) 2. Period 2:Treatment B: 8 mg ORMD-0801; one 8 mg capsule three times a day (TID) 45-90 minutes before meals 3. Period 3: Treatment A: 24 mg ORMD-0801;(16 mg + 8 mg capsules) Once Daily (QD) at Bedtime Treatment B: 8 mg ORMD-0801; one 8 mg capsule three times a day (TID) 45-90 minutes before meals

Drug: ORMD-0801 Treatment A; Drug: ORMD-0801 Treatment B; Other: Placebo

Interventions

ORMD-0801 Treatment A DRUG

Treatment A: 24 mg (16 mg capsule + 8 mg capsule) Once Daily (QD) at bedtime

Also known as: Oral Insulin

Placebo then Treatment A then Treatment B; Placebo then Treatment B then Treatment A

ORMD-0801 Treatment B DRUG

Treatment B: 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals

Also known as: Oral Insulin

Placebo then Treatment A then Treatment B; Placebo then Treatment B then Treatment A

Placebo OTHER

Fish oil capsule

Placebo then Treatment A then Treatment B; Placebo then Treatment B then Treatment A

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.
• Body mass index (BMI) of 19-30 kg/m2 at Screening and stable weight, with no more than 5 kg gain or loss in the 3 months prior to Screening.
• T1D subjects must have:
• A documented history of type 1 diabetes for at least 6 months
• Should be on an MDI regimen
• C peptide levels of ˂ 0.7 ng/mL
• HbA1C ≥ 6.5% to ≤10%
• Females of childbearing potential must have a negative serum pregnancy test result at Screening.
• Females who are not of childbearing potential are defined as:
• post-menopausal (defined as at least 12 months with no menses in women ≥45 years of age) or
• has had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or occlusion at least 6 weeks prior to Screening
• Subjects who are of childbearing potential must:
• a. agree to remain abstinent from heterosexual activity† or agree to use (or have their partner use) acceptable contraception to prevent pregnancy within the projected duration of the trial and for 14 days after the last dose of blinded investigational product. Two methods of contraception will be used to avoid pregnancy. Acceptable combinations of methods include: i. Use of one of the following double-barrier methods: diaphragm with spermicide and a condom; cervical cap and a condom; or a contraceptive sponge and condom ii. Use of hormonal contraception (any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent \[including oral, subcutaneous, intrauterine and intramuscular agents, and cutaneous patch\]) with one of the following: diaphragm with spermicide; cervical cap; contraceptive sponge; condom; vasectomy; or IUD. iii. Use of an IUD with one of the following: condom; diaphragm with spermicide; contraceptive sponge; vasectomy; or hormonal contraception (see above).
• iv. Vasectomy with one of the following: diaphragm with spermicide; cervical cap; contraceptive sponge; condom; IUD; or hormonal contraception (see above).
• †Abstinence can be used as the sole method of contraception if it is in line with the subject's preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ethics committees. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.

You may not qualify if:

• Clinical diagnosis of type 2 diabetes;
• Evidence of unawareness of hypoglycemia unawareness, a documented plasma glucose ≤50 mg/dL in the absence of symptoms of hypoglycemia at Screening.
• FPG \>300 mg/dL at Screening; a single repeat test is allowable.
• Use of the following medications:
• 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.
• Laboratory abnormalities at Screening including:
• 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.
• Subject has a Screening systolic blood pressure ≥165 mmHg or diastolic blood pressure ≥100 mmHg. Subjects will be allowed to take a BP rescue medication.
• Any clinically significant ECG abnormality at Screening or cardiovascular disease. Clinically significant cardiovascular disease will include:
• a. History of stroke, transient ischemic attack, or myocardial infarction within 6 months prior to Screening,
• History of or currently have New York Heart Associate Class II-IV heart failure prior to Screening.

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 1

Interventions

Insulin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Miriam Kidron, PhD
• Organization: Oramed, Ltd.

miriam@oramed.com

+972-2-566-0001

Study Officials

• Miriam Kidron, PhD

  Oramed Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-Label
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label crossover study in which all subjects will receive placebo run-in during Period 1 followed by Period 2, where subjects will be randomly assigned to either daily Treatment A (taken at Bedtime) and Treatment B (taken daily before each of three daily meals). At visit 5, the start of Period 3, subjects will stop their treatment (either A or B) and be CROSSED OVER to the other treatment (patients on treatment A during Period 2 will be crossed over to Treatment B and patients who were on Treatment B during Period 2 will be crossed over to Treatment A in Period 3).

Study Record Dates

• First Submitted: October 31, 2019
• First Posted: November 4, 2019
• Study Start: October 17, 2019
• Primary Completion: February 6, 2020
• Study Completion: March 12, 2020
• Last Updated: June 2, 2022
• Results First Posted: June 2, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)