Safety, Pharmacokinetics and Pharmacodynamics of Multiple Oral Bedtime Doses of ORMD-0801 in Adult Patients With Type 2 Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Oramed, Ltd.
Information provided by (Responsible Party):
Oramed, Ltd. Identifier:
First received: June 19, 2013
Last updated: July 17, 2013
Last verified: July 2013

The purpose of this study is to test the safety and pharmacodynamics of an oral formulation of insulin in subjects with Type 2 Diabetes.

Condition Intervention Phase
Diabetes Mellitus Type 2
Drug: ORMD-0801 Dose # 1
Drug: ORMD-0801 Dose # 2
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of Multiple Oral Bedtime Doses of ORMD-0801(Insulin Capsules) in Adult Patients With Type 2 Diabetes Mellitus Who Are Inadequately Controlled With Diet and Exercise or Diet, Exercise and Metformin

Resource links provided by NLM:

Further study details as provided by Oramed, Ltd.:

Primary Outcome Measures:
  • Safety and Tolerability as assessed by numbers of adverse events [ Time Frame: Eight (8) days ] [ Designated as safety issue: Yes ]
    Number of adverse events collected during study

Secondary Outcome Measures:
  • The effect of ORMD-0801 on weighted mean night time glucose levels of continuous glucose monitor (CGM) data at the end of the seven (7)- day treatment period as determined by comparison to the effect in the group receiving placebo [ Time Frame: Seven (7) days ] [ Designated as safety issue: Yes ]
  • To evaluate the pharmacokinetics of ORMD-0801 on area under the curve (AUC), Cmax, Tmax, and T½ [ Time Frame: Nineteen (19) time points on each of two (2) days ] [ Designated as safety issue: Yes ]
  • To evaluate changes from baseline in fasting blood (finger stick) glucose [ Time Frame: Screening + seventeen (17) days ] [ Designated as safety issue: Yes ]
  • The effect of ORMD-0801 on Morning fasting blood glucose by finger stick compared to pre-treatment placebo run-in period [ Time Frame: average of last five (5) of the seven (7) days ] [ Designated as safety issue: Yes ]
  • The effect of ORMD-0801 on morning fasting serum insulin compared to placebo [ Time Frame: Screening + four (4) days ] [ Designated as safety issue: Yes ]
  • The effect of ORMD-0801 on morning fasting C-peptide compared to placebo [ Time Frame: Screening + four (4) days ] [ Designated as safety issue: Yes ]
  • The effect of ORMD-0801 on morning fasting blood glucose compared to placebo [ Time Frame: Screening + four (4) days ] [ Designated as safety issue: Yes ]
  • The effect of ORMD-0801 on morning fasting blood glucose by finger stick compared to group receiving placebo [ Time Frame: average of last of the seven (7) days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: June 2013
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ORMD-0801 Dose # 1
Oral Insulin Formulation
Drug: ORMD-0801 Dose # 1
Oral Insulin Formulation
Other Name: Oral Insulin
Experimental: ORMD-0801 Dose # 2
Oral Insulin Formulation
Drug: ORMD-0801 Dose # 2
Oral Insulin Formulation
Other Name: Oral Insulin
Placebo Comparator: Placebo
Oil Capsules
Drug: Placebo
Oil Capsules
Other Name: Placebo

Detailed Description:

This is a single-center, Phase II(a), randomized, double-blind, placebo-controlled, parallel group, inpatient study preceded by a 5-day single-blind outpatient placebo run-in period.


Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male or female patients, age 20 to 70 years, inclusive with type 2 diabetes;
  • At time of randomization, patients will be treated for their diabetes by diet and exercise, or by diet, exercise and metformin (>1000 mg/day; any type and regimen). Patients will have been on a stable regimen of metformin (defined as the same metformin dose and type) for at least 6 weeks prior to entering the placebo run-in period. Other anti-diabetic agents will not have been in use for the 6 weeks prior to entering the placebo run-in period;
  • Body Mass Index (BMI) between 25 and 40 kg/m2, inclusive;
  • Hemoglobin A1c (HbA1c) between 6.5 -10.5%, inclusive, prior to randomization)
  • Fasting plasma glucose greater than or equal to 126 mg/dL (8.3 mmo1/L) prior to randomization;
  • No tobacco or nicotine use within 10 weeks prior to screening;
  • Females of child-bearing potential must have a negative serum pregnancy test result at screening and a negative urine pregnancy test at Visit 3. Females of non-childbearing potential are defined as postmenopausal who:

    1. had more than 24 months since last menstrual cycle with menopausal levels of follicle stimulating hormone(FSH);
    2. are greater than 55 years old; or
    3. are surgically menopausal.

Exclusion Criteria:

  • Presence of any clinically significant endocrine disease according to the Investigator;
  • Clinical diagnosis of Type 1 diabetes;
  • Fasting plasma glucose >260 mg/dL at the end of washout/stabilization/run-in periods;
  • Evidence of unawareness of hypoglycemia, a documented plasma glucose ≤50 mg/dL in the absence of symptoms of hypoglycemia;
  • Presence of any clinically significant condition that might interfere with the evaluation of study medication;
  • Presence or history of cancer within the past five years with the exception of adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer;
  • Laboratory abnormalities at screening including

    1. C-peptide < 1.0 ng/mL;
    2. Positive pregnancy test in females of childbearing potential (at screening and start of run-in period);
    3. Abnormal serum thyrotropin (TSH) levels > 1.5 times the upper limit of normal;
    4. Positive test for hepatitis B surface antigen and/or hepatitis C antibody;
    5. Positive test for HIV;
    6. Any relevant abnormality interfering with the efficacy or the safety assessments during study drug administration;
  • Use of the following medications

    1. History of use of insulin for no more than 1 week in the last 6 months and none in the last 6 weeks prior to randomization;
    2. History of use of aprotinin at any time prior to the screening visit;
    3. Administration of anti-diabetic drugs other than metformin within 6 weeks prior to run-in period;
    4. Administration of thiazolidinedione treatment within 3 months prior to randomization;
    5. Administration of thyroid preparations or thyroxine (except in patients on stable replacement therapy) within 6 weeks prior to screening visit;
    6. Administration of systemic long-acting corticosteroids within two months or prolonged use of other systemic corticosteroids or inhaled corticosteroids within 30 days prior to screening visit;
    7. Use of medications known to modify glucose metabolism or to decrease the ability to recover from hypoglycemia such as oral, parenteral, and inhaled steroids, beta blockers (with the exception of beta blocker ophthalmic solutions for glaucoma or ocular hypertension), and immunosuppressive or immunomodulating agents.
  • History of severe or multiple allergies;
  • History of tobacco or nicotine use within 10 weeks prior to screening
  • Patient is on a weight loss program and is not in the maintenance phase, or patient that started weight loss medication within 8 weeks prior to screening;
  • Pregnancy or breast-feeding;
  • Patient has a screening visit systolic blood pressure of ≥165 mm Hg or diastolic blood pressure of ≥100 mm Hg. Patients will be allowed to take a BP rescue medication as long as it does not affect glucose metabolism (e.g., diuretics) or sensation of hypoglycemia (e.g., beta-blockers);
  • Patient is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence;
  • Elevated liver enzymes (alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase) greater than 2 times the upper limit of normal at screening;
  • Very high triglyceride level (>600 mg/dL) at screening;
  • Any clinically significant ECG abnormality at screening or cardiovascular disease. Clinically significant cardiovascular disease will include

    1. history of stroke, transient ischemic attack, or myocardial infarction within 6 months prior to screening;
    2. history of or currently have New York Heart Associate Class II-IV heart failure prior to screening; or
    3. uncontrolled hypertension defined as blood pressure ≥180 mmHg (systolic) or ≥110 mmHG (diastolic) at screening or at Visit 2;
  • One or more contraindications to metformin;
  • History of gastrointestinal disorders with the potential to interfere with drug absorption;

At the Principal Investigator's discretion, any condition or other factor that is deemed unsuitable for patient enrollment into the study

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01889667

Contact: Miriam Kidron, Ph.D.

United States, California
Orange County Research Center Recruiting
Tustin, California, United States, 92780
Contact: Joel M Neutel, M. D.    714-550-9990      
Sponsors and Collaborators
Oramed, Ltd.
Study Director: Joel M Neutel, M. D. Orange County Research Center
  More Information

No publications provided

Responsible Party: Oramed, Ltd. Identifier: NCT01889667     History of Changes
Other Study ID Numbers: ORA-D-009, ORMD-0801
Study First Received: June 19, 2013
Last Updated: July 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Oramed, Ltd.:
Oral Insulin
Diabetes Mellitus Type 2

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs processed this record on October 20, 2014