Diabetes Mellitus Type 2
Conditions
Keywords
Oral Insulin, Diabetes Mellitus Type 2, Safety, Pharmacodynamics, Pharmacokinetics
Brief summary
The purpose of this study is to test the safety and pharmacodynamics of an oral formulation of insulin in subjects with Type 2 Diabetes.
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.
Interventions
DRUGORMD-0801 Dose # 1
Oral Insulin Formulation
DRUGORMD-0801 Dose # 2
Oral Insulin Formulation
DRUGPlacebo
Oil Capsules
Sponsors
Integrium
Oramed, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients, age 20 to 70 years, inclusive with T2DM; * At randomization, patients are treated for diabetes by diet and exercise, or by diet, exercise and metformin (\>1000 mg/day; any type and regimen). Patients 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 not in use for the 6 weeks prior to entering the placebo run-in period; * 25 kg/m2 ≤ BMI ≤ 40 kg/m2 * 6.5% ≤ HbA1c ≤ 10.5%, prior to randomization) * Fasting plasma glucose ≥ 126 mg/dL (8.3 mmo1/L) prior to randomization; * No tobacco or nicotine use within 10 wks 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 FSH; 2. age \> 55 years old; or 3. are surgically menopausal.
Exclusion criteria
* Presence of any clinically significant endocrine disease according to the PI; * Clinical diagnosis of T1DM; * 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 5 yrs. with the exception of adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer; * Laboratory abnormalities at screening: 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 TSH levels \> 1.5 x 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 wk in the last 6 mos and none in the last 6 wks 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 wks 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 wks 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 wks 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 ALT, AST, alkaline phosphatase) \> 2 x the upper limit of normal at screening; * Very high triglyceride level (\>600 mg/dL) at screening; * ECG abnormality at screening or CV. Clinically significant CV will include 1. history of stroke, transient ischemic attack, or MCI within 6 months prior to screening; 2. history of or currently have NYHA Class II-IV heart failure prior to screening; or 3. uncontrolled hypertension defined as BP ≥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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Safety and Tolerability of ORMD-0801. | Eight (8) days | Number of Hypoglycemic events, serious adverse events, and adverse events related to the study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Effect of ORMD-0801 on Mean Night Time Glucose as Measured by Contiuous Glucose Monitoring (CGM) | Seven (7) days, and last two days (Day 6 and day 7) | Difference between concentration of Nightime Glucose of patients on Placebo and concentration of Nightime Glucose of patients on ORMD-0801 |
| The Effect of ORMD-0801 on Mean Daytime Glucose as Measured by Contiuous Glucose Monitoring (CGM) | Seven (7) days, and last two days (Day 6 and day 7) | Difference between concentration of Mean Daytime Glucose of patients on Placebo and concentration of Mean Daytime Glucose of patients on ORMD-0801 |
| The Effect of ORMD-0801 on Morning Fasting Serum Insulin | Screening, Day 2. Day 9 | Difference between concentration of Morning fasting serum insulin of patients on Placebo and concentration of Morning fasting C-peptide of patients on ORMD-0801 |
| The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo | Screening, Day 2, Day 9 | Difference between concentration of Morning fasting C-peptide of patients on Placebo and concentration of Morning fasting C-peptide of patients on ORMD-0801 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ORMD-0801 Dose # 1 Oral Insulin Formulation
ORMD-0801 Dose # 1: Oral Insulin Formulation 8mg + 8 mg capsules | 10 |
| ORMD-0801 Dose # 2 Oral Insulin Formulation
ORMD-0801 Dose # 2: Oral Insulin Formulation 8 mg + 16 mg capsules | 10 |
| Placebo Oil Capsules
Placebo: Oil Capsules | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | ORMD-0801 Dose # 1 | Total | Placebo | ORMD-0801 Dose # 2 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 30 Participants | 10 Participants | 10 Participants |
| Age, Continuous | 54.1 years STANDARD_DEVIATION 4.9 | 55.3 years STANDARD_DEVIATION 6.89 | 53.6 years STANDARD_DEVIATION 12 | 57.4 years STANDARD_DEVIATION 4.7 |
| Region of Enrollment United States | 10 participants | 30 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 5 Participants | 15 Participants | 7 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 15 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 10 | 4 / 10 | 5 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Evaluate the Safety and Tolerability of ORMD-0801.
Number of Hypoglycemic events, serious adverse events, and adverse events related to the study drug
Time frame: Eight (8) days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ORMD-0801 Dose # 1 | Evaluate the Safety and Tolerability of ORMD-0801. | 0 Number of Events |
| ORMD-0801 Dose # 2 | Evaluate the Safety and Tolerability of ORMD-0801. | 0 Number of Events |
| Placebo | Evaluate the Safety and Tolerability of ORMD-0801. | 0 Number of Events |
Secondary
The Effect of ORMD-0801 on Mean Daytime Glucose as Measured by Contiuous Glucose Monitoring (CGM)
Difference between concentration of Mean Daytime Glucose of patients on Placebo and concentration of Mean Daytime Glucose of patients on ORMD-0801
Time frame: Seven (7) days, and last two days (Day 6 and day 7)
Population: Per Protocol (PP) population, consisting of all study completers with an endpoint of adequate weighted mean nighttime glucose and no major protocol violations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ORMD-0801 Dose # 1 | The Effect of ORMD-0801 on Mean Daytime Glucose as Measured by Contiuous Glucose Monitoring (CGM) | All Seven Days | 152.55 mg/dL | Standard Deviation 36.986 |
| ORMD-0801 Dose # 1 | The Effect of ORMD-0801 on Mean Daytime Glucose as Measured by Contiuous Glucose Monitoring (CGM) | Last two days (day 6 and day 7) | 153.23 mg/dL | Standard Deviation 40.16 |
| ORMD-0801 Dose # 2 | The Effect of ORMD-0801 on Mean Daytime Glucose as Measured by Contiuous Glucose Monitoring (CGM) | All Seven Days | 163.05 mg/dL | Standard Deviation 30.282 |
| ORMD-0801 Dose # 2 | The Effect of ORMD-0801 on Mean Daytime Glucose as Measured by Contiuous Glucose Monitoring (CGM) | Last two days (day 6 and day 7) | 158.58 mg/dL | Standard Deviation 40.672 |
| Placebo | The Effect of ORMD-0801 on Mean Daytime Glucose as Measured by Contiuous Glucose Monitoring (CGM) | All Seven Days | 175.99 mg/dL | Standard Deviation 61.115 |
| Placebo | The Effect of ORMD-0801 on Mean Daytime Glucose as Measured by Contiuous Glucose Monitoring (CGM) | Last two days (day 6 and day 7) | 176.06 mg/dL | Standard Deviation 63.698 |
Secondary
The Effect of ORMD-0801 on Mean Night Time Glucose as Measured by Contiuous Glucose Monitoring (CGM)
Difference between concentration of Nightime Glucose of patients on Placebo and concentration of Nightime Glucose of patients on ORMD-0801
Time frame: Seven (7) days, and last two days (Day 6 and day 7)
Population: Per Protocol (PP) population, consisting of all study completers with an endpoint of adequate weighted mean nighttime glucose and no major protocol violations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ORMD-0801 Dose # 1 | The Effect of ORMD-0801 on Mean Night Time Glucose as Measured by Contiuous Glucose Monitoring (CGM) | Last two days (day 6 and day 7) | 135.64 mg/DL | Standard Deviation 39.4 |
| ORMD-0801 Dose # 1 | The Effect of ORMD-0801 on Mean Night Time Glucose as Measured by Contiuous Glucose Monitoring (CGM) | All Seven Days | 139.73 mg/DL | Standard Deviation 38.861 |
| ORMD-0801 Dose # 2 | The Effect of ORMD-0801 on Mean Night Time Glucose as Measured by Contiuous Glucose Monitoring (CGM) | Last two days (day 6 and day 7) | 150.24 mg/DL | Standard Deviation 49.264 |
| ORMD-0801 Dose # 2 | The Effect of ORMD-0801 on Mean Night Time Glucose as Measured by Contiuous Glucose Monitoring (CGM) | All Seven Days | 149.38 mg/DL | Standard Deviation 38.249 |
| Placebo | The Effect of ORMD-0801 on Mean Night Time Glucose as Measured by Contiuous Glucose Monitoring (CGM) | Last two days (day 6 and day 7) | 167.95 mg/DL | Standard Deviation 64.172 |
| Placebo | The Effect of ORMD-0801 on Mean Night Time Glucose as Measured by Contiuous Glucose Monitoring (CGM) | All Seven Days | 165.85 mg/DL | Standard Deviation 60.76 |
Secondary
The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo
Difference between concentration of Morning fasting C-peptide of patients on Placebo and concentration of Morning fasting C-peptide of patients on ORMD-0801
Time frame: Screening, Day 2, Day 9
Population: Modified intention-to-treat (mITT) population consisting of all randomized patients who took at least one dose of study medication and who had at least one night of CGM monitoring
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ORMD-0801 Dose # 1 | The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo | Day 2 | 3.180 mg/dL | Standard Deviation 1.6593 |
| ORMD-0801 Dose # 1 | The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo | Screening | 4.233 mg/dL | Standard Deviation 2.3869 |
| ORMD-0801 Dose # 1 | The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo | Day 9 | 3.875 mg/dL | Standard Deviation 1.6927 |
| ORMD-0801 Dose # 2 | The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo | Day 2 | 3.064 mg/dL | Standard Deviation 0.92 |
| ORMD-0801 Dose # 2 | The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo | Screening | 3.125 mg/dL | Standard Deviation 1.3372 |
| ORMD-0801 Dose # 2 | The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo | Day 9 | 3.090 mg/dL | Standard Deviation 1.1021 |
| Placebo | The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo | Screening | 5.159 mg/dL | Standard Deviation 4.9825 |
| Placebo | The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo | Day 9 | 2.715 mg/dL | Standard Deviation 0.8506 |
| Placebo | The Effect of ORMD-0801 on Morning Fasting C-peptide Compared to Placebo | Day 2 | 2.400 mg/dL | Standard Deviation 0.9419 |
Secondary
The Effect of ORMD-0801 on Morning Fasting Serum Insulin
Difference between concentration of Morning fasting serum insulin of patients on Placebo and concentration of Morning fasting C-peptide of patients on ORMD-0801
Time frame: Screening, Day 2. Day 9
Population: Modified intention-to-treat (mITT) population consisting of all randomized patients who took at least one dose of study medication and who had at least one night of CGM monitoring
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ORMD-0801 Dose # 1 | The Effect of ORMD-0801 on Morning Fasting Serum Insulin | Day 2 | 11.93 mg/dL | Standard Deviation 10.122 |
| ORMD-0801 Dose # 1 | The Effect of ORMD-0801 on Morning Fasting Serum Insulin | Screening | 20.80 mg/dL | Standard Deviation 18.984 |
| ORMD-0801 Dose # 1 | The Effect of ORMD-0801 on Morning Fasting Serum Insulin | Day 9 | 15.70 mg/dL | Standard Deviation 8.559 |
| ORMD-0801 Dose # 2 | The Effect of ORMD-0801 on Morning Fasting Serum Insulin | Day 2 | 12.94 mg/dL | Standard Deviation 7.472 |
| ORMD-0801 Dose # 2 | The Effect of ORMD-0801 on Morning Fasting Serum Insulin | Screening | 17.34 mg/dL | Standard Deviation 12.225 |
| ORMD-0801 Dose # 2 | The Effect of ORMD-0801 on Morning Fasting Serum Insulin | Day 9 | 15.51 mg/dL | Standard Deviation 14.924 |
| Placebo | The Effect of ORMD-0801 on Morning Fasting Serum Insulin | Screening | 34.51 mg/dL | Standard Deviation 64.375 |
| Placebo | The Effect of ORMD-0801 on Morning Fasting Serum Insulin | Day 9 | 9.85 mg/dL | Standard Deviation 3.977 |
| Placebo | The Effect of ORMD-0801 on Morning Fasting Serum Insulin | Day 2 | 9.01 mg/dL | Standard Deviation 4.665 |