Type 1 Diabetes
Conditions
Keywords
Oral Insulin
Brief summary
ORAMED has developed an oral insulin that, in preliminary studies, has shown promise. In the present study investigators will perform a pharmacodynamic/pharmacokinetic study to evaluate this novel insulin preparation as a potential therapeutic option in diabetic patients.
Detailed description
Insulin therapy is an absolute requirement in type 1 diabetic patients. Multiple injections present a barrier to achieving normal/near-normal glucose control in diabetic patients (1). Therefore, there has been considerable interest in developing alternative routes of insulin administration. ORAMED has developed an oral insulin that, in preliminary studies, has shown promise. In the present study investigators will perform a pharmacodynamic/pharmacokinetic study to evaluate this novel insulin preparation as a potential therapeutic option in type 1 diabetic patients. 10 type 1 diabetic subjects will be studied. Each subject will be studied on three occasions with an interval of 3 days to 4 weeks between each study. During each study subjects will receive one intervention at a time in random order: (i) two 8 mg ORAMED capsule containing insulin; (ii) three 8 mg ORAMED capsules containing insulin; (iii) one 16 mg ORAMED capsule containing insulin. If the fasting plasma glucose is \>200mg/dl on the procedure day, the procedure will be rescheduled. Prior to each study subjects will refrain from eating (except water) after 10 at night and report to the Clinical Research Center at approximately 7 in the morning. A catheter will be placed in an antecubital vein and a prime (40 microCuries x fasting plasma glucose/100) - continuous (0.4 microCuries/min) infusion of tritiated glucose will be started and continued until the end of the study. Plasma glucose will be monitored and if necessary during the 1st hour of tracer equilibration, a small amount of IV regular insulin will be administered to obtain a fasting plasma glucose of 100-130mg/dl. After a 3-hour tracer equilibration, subjects will ingest the ORAMED capsule containing insulin and a variable infusion of 20% glucose will be started to maintain the plasma glucose concentration between 100-120 mg/dl. Plasma samples for glucose, insulin, glucagon, and free fatty acid (FFA) concentrations and tritiated glucose radioactivity will be obtained every 5-15 minutes for 4 hours following the ingestion of the ORAMED capsule containing insulin. Calculations: Following an overnight fast, steady state conditions prevail and the basal rate of glucose appearance equals the rate of glucose disappearance and is calculated as the tritiated glucose infusion rate divided by the tritiated glucose specific activity. Under postabsorptive conditions, Basal rate of glucose appearance primarily reflects hepatic glucose production (2). Following the ingestion of oral insulin, non-steady state conditions prevail and Ra and Rd are calculated using Steele's equation (3). Endogenous (primarily reflects liver) glucose production is calculated by subtracting the exogenous glucose infusion rate from the tracer-derived rate of glucose appearance. Endogenous rate of glucose disappearance reflects glucose uptake by all tissues in the body, but primarily reflects skeletal muscle (4). Sample Size: The present study represents a pilot study to gain information about the absorption of oral insulin and its effect on hepatic and peripheral (skeletal muscle) glucose metabolism. This information will be used to determine whether the ORAMED oral insulin preparation represents a viable option to treat diabetic subjects, to gain information about the dose response effect of ORAMED insulin on glucose metabolism, and to provide quantitative data about the effect of oral insulin on hepatic and peripheral (muscle) glucose metabolism. Therefore, the investigators conservatively have set the sample size at 10.
Interventions
DRUGORMD-0801 capsules- 2x8mg
Participants who receive this intervention first, then receive either ORMD-0801- 3x8mg or 1x16mg dose after a 3 day to 4 week interval. Participants receiving this drug as the second drug intervention will then receive the third intervention after a 3 day to 4 week interval. ORMD-0801 capsules are an oral insulin that has shown promise in preliminary studies. Investigators will evaluate this novel insulin preparation as a potential therapeutic option in diabetic patients.
DRUGORMD-0801 capsules- 3x8mg
Participants who receive this intervention first, then receive either ORMD-0801- 2x8mg or 1x16mg dose after a 3 day to 4 week interval. Participants receiving this drug as the second drug intervention will then receive the third intervention after a 3 day to 4 week interval. ORMD-0801 capsules are an oral insulin that has shown promise in preliminary studies. Investigators will evaluate this novel insulin preparation as a potential therapeutic option in diabetic patients.
DRUGORMD-0801 capsules- 1x16mg
Participants who receive this intervention first, then receive either ORMD-0801- 2x8mg or 3x8mg dose after a 3 day to 4 week interval. Participants receiving this drug as the second drug intervention will then receive the third intervention after a 3 day to 4 week interval. ORMD-0801 capsules are an oral insulin that has shown promise in preliminary studies. Investigators will evaluate this novel insulin preparation as a potential therapeutic option in diabetic patients.
Sponsors
Oramed, Ltd.
The University of Texas Health Science Center at San Antonio
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Must be between 18 and 70 years of age * Must have type 1 diabetes * Must be in good general health by routine history and physical exam * A1c \<10.0% * BMI = 18-40 kg/m2 * On no medications known to affect glucose metabolism other than insulin * Hematocrit ≥ 34 vol% * Liver Function Tests \< 3 x Upper Normal Limit * Plasma creatinine \< 1.8 mg/dl
Exclusion criteria
* Under 18 years of age and over 70 years of age * Does not have type 1 diabetes * A1c \> 10.0% * BMI \< 18 or \> 40 kg.m2 * On medications known to affect glucose metabolism other than insulin * Hematocrit ≤ 34 vol% * Liver Function Tests \>3 x Upper Normal Limit * Plasma creatinine \> 1.8 mg/dl
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Glucose Production (Co-primary Outcome) | Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month | Tritiated glucose infusion during procedures (Baseline and every 30 minutes during procedures) Calculated from plasma(mg/kg-minute). Averaged every 30 minutes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Insulin Concentrations | Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month | Baseline and every 15 minutes during procedures (microIU/mL). |
| Plasma Glucose Concentrations | Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month | Measured at baseline and every 5 minutes during the procedures(mg/dL), Averaged over 30 minute intervals during the procedure |
| Plasma Glucagon Concentrations | Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month | Measured at baseline and every 30 minutes during the procedures (pg/mL) |
| Plasma Free Fatty Acid Concentrations | Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month | Measured at baseline and every 30 minutes during the procedures (micro mol/L) |
Countries
United States
Participant flow
Pre-assignment details
Subjects will be assigned to all 3 interventions during the study. One intervention will be assigned at a time, but in random order, with a 3 day to 4 week interval between interventions.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Two 8 mg ORAMED capsules containing insulin then Three 8mg ORAMED capsules containing insulin then One 16mg ORAMED capsules containing insulin
ORMD-0801 capsules: ORMD-0801 capsules are an oral insulin that has shown promise in preliminary studies. Investigators will evaluate this novel insulin preparation as a potential therapeutic option in diabetic patients. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 14 |
| Race/Ethnicity, Customized Asian or Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Black-non Hispanic | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 3 Participants |
| Race/Ethnicity, Customized White non-Hispanic | 6 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 0 / 11 | 1 / 11 | 0 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 10 |
Outcome results
Primary
Hepatic Glucose Production (Co-primary Outcome)
Tritiated glucose infusion during procedures (Baseline and every 30 minutes during procedures) Calculated from plasma(mg/kg-minute). Averaged every 30 minutes.
Time frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 61-90 minutes | 1.5 mg/kg-minute | Standard Error 0.2 |
| 2X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 211-240 | 1.4 mg/kg-minute | Standard Error 0.2 |
| 2X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 121-150 minutes | 1.5 mg/kg-minute | Standard Error 0.2 |
| 2X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 91-120 minutes | 1.6 mg/kg-minute | Standard Error 0.2 |
| 2X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | -180 to 0 | 2.0 mg/kg-minute | Standard Error 0.1 |
| 2X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 181-210 minutes | 1.5 mg/kg-minute | Standard Error 0.2 |
| 2X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 31-60 minutes | 1.6 mg/kg-minute | Standard Error 0.2 |
| 2X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 1-30 minutes | 1.8 mg/kg-minute | Standard Error 0.2 |
| 2X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 151-180 minutes | 1.6 mg/kg-minute | Standard Error 0.2 |
| 3X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 91-120 minutes | 1.7 mg/kg-minute | Standard Error 0.2 |
| 3X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | -180 to 0 | 2.0 mg/kg-minute | Standard Error 0.1 |
| 3X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 1-30 minutes | 1.9 mg/kg-minute | Standard Error 0.1 |
| 3X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 31-60 minutes | 1.7 mg/kg-minute | Standard Error 0.2 |
| 3X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 61-90 minutes | 1.6 mg/kg-minute | Standard Error 0.1 |
| 3X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 121-150 minutes | 1.6 mg/kg-minute | Standard Error 0.2 |
| 3X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 151-180 minutes | 1.6 mg/kg-minute | Standard Error 0.2 |
| 3X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 181-210 minutes | 1.5 mg/kg-minute | Standard Error 0.2 |
| 3X 8mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 211-240 | 1.5 mg/kg-minute | Standard Error 0.2 |
| 1X 16mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 31-60 minutes | 2.1 mg/kg-minute | Standard Error 0.4 |
| 1X 16mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | -180 to 0 | 2.1 mg/kg-minute | Standard Error 0.3 |
| 1X 16mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 151-180 minutes | 1.7 mg/kg-minute | Standard Error 0.5 |
| 1X 16mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 1-30 minutes | 2.1 mg/kg-minute | Standard Error 0.3 |
| 1X 16mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 211-240 | 1.5 mg/kg-minute | Standard Error 0.3 |
| 1X 16mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 91-120 minutes | 1.7 mg/kg-minute | Standard Error 0.5 |
| 1X 16mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 61-90 minutes | 1.9 mg/kg-minute | Standard Error 0.4 |
| 1X 16mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 181-210 minutes | 1.4 mg/kg-minute | Standard Error 0.2 |
| 1X 16mg Oral Insulin Capsules | Hepatic Glucose Production (Co-primary Outcome) | 121-150 minutes | 1.6 mg/kg-minute | Standard Error 0.5 |
Secondary
Plasma Free Fatty Acid Concentrations
Measured at baseline and every 30 minutes during the procedures (micro mol/L)
Time frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month
Population: Wako Calorometric
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 121-150 minutes | 528 mmol/L | Standard Error 74 |
| 2X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | Baseline | 380 mmol/L | Standard Error 68 |
| 2X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 1-30 minutes | 408 mmol/L | Standard Error 76 |
| 2X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 31-60 minutes | 463 mmol/L | Standard Error 78 |
| 2X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 61-90 minutes | 472 mmol/L | Standard Error 74 |
| 2X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 91-120 minutes | 495 mmol/L | Standard Error 84 |
| 2X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 151-180 minutes | 547 mmol/L | Standard Error 80 |
| 2X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 181-210 minutes | 523 mmol/L | Standard Error 75 |
| 2X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 211-240 minutes | 490 mmol/L | Standard Error 69 |
| 3X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 91-120 minutes | 473 mmol/L | Standard Error 94 |
| 3X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 151-180 minutes | 486 mmol/L | Standard Error 95 |
| 3X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | Baseline | 402 mmol/L | Standard Error 80 |
| 3X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 181-210 minutes | 485 mmol/L | Standard Error 97 |
| 3X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 121-150 minutes | 501 mmol/L | Standard Error 97 |
| 3X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 1-30 minutes | 465 mmol/L | Standard Error 81 |
| 3X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 61-90 minutes | 545 mmol/L | Standard Error 102 |
| 3X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 211-240 minutes | 486 mmol/L | Standard Error 95 |
| 3X 8mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 31-60 minutes | 533 mmol/L | Standard Error 96 |
| 1X 16mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 211-240 minutes | 538 mmol/L | Standard Error 74 |
| 1X 16mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 61-90 minutes | 489 mmol/L | Standard Error 63 |
| 1X 16mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 181-210 minutes | 533 mmol/L | Standard Error 63 |
| 1X 16mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 91-120 minutes | 506 mmol/L | Standard Error 56 |
| 1X 16mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 121-150 minutes | 509 mmol/L | Standard Error 54 |
| 1X 16mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 31-60 minutes | 448 mmol/L | Standard Error 61 |
| 1X 16mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | Baseline | 410 mmol/L | Standard Error 87 |
| 1X 16mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 151-180 minutes | 545 mmol/L | Standard Error 53 |
| 1X 16mg Oral Insulin Capsules | Plasma Free Fatty Acid Concentrations | 1-30 minutes | 467 mmol/L | Standard Error 69 |
p-value: <0.05ANOVA
Secondary
Plasma Glucagon Concentrations
Measured at baseline and every 30 minutes during the procedures (pg/mL)
Time frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month
Population: Glucagon measured by RIA kit, EMD Millipore.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 61-90 minutes | 29 pg/mL | Standard Error 3 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 211-240 minutes | 24 pg/mL | Standard Error 3 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 121-150 minutes | 26 pg/mL | Standard Error 3 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 91-120 minutes | 28 pg/mL | Standard Error 4 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | -180 to 0 minutes | 29 pg/mL | Standard Error 4 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 181 to 210 minutes | 23 pg/mL | Standard Error 3 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 31-60 minutes | 27 pg/mL | Standard Error 3 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 1-30 minutes | 29 pg/mL | Standard Error 4 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 151-180 minutes | 26 pg/mL | Standard Error 4 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 91-120 minutes | 34 pg/mL | Standard Error 4 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | -180 to 0 minutes | 37 pg/mL | Standard Error 4 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 1-30 minutes | 38 pg/mL | Standard Error 5 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 31-60 minutes | 37 pg/mL | Standard Error 4 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 61-90 minutes | 36 pg/mL | Standard Error 4 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 121-150 minutes | 35 pg/mL | Standard Error 4 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 151-180 minutes | 35 pg/mL | Standard Error 4 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 181 to 210 minutes | 35 pg/mL | Standard Error 4 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 211-240 minutes | 36 pg/mL | Standard Error 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 31-60 minutes | 34 pg/mL | Standard Error 5 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucagon Concentrations | -180 to 0 minutes | 37 pg/mL | Standard Error 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 151-180 minutes | 33 pg/mL | Standard Error 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 1-30 minutes | 36 pg/mL | Standard Error 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 211-240 minutes | 32 pg/mL | Standard Error 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 91-120 minutes | 33 pg/mL | Standard Error 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 61-90 minutes | 34 pg/mL | Standard Error 5 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 181 to 210 minutes | 31 pg/mL | Standard Error 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucagon Concentrations | 121-150 minutes | 34 pg/mL | Standard Error 4 |
Secondary
Plasma Glucose Concentrations
Measured at baseline and every 5 minutes during the procedures(mg/dL), Averaged over 30 minute intervals during the procedure
Time frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 210 to 240 minutes | 111 mg/dl | Standard Error 7 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 121 to 150 minutes | 105 mg/dl | Standard Error 5 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 61-90 minutes | 100 mg/dl | Standard Error 6 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 91-120 minutes | 103 mg/dl | Standard Error 5 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 181 to 210 minutes | 110 mg/dl | Standard Error 6 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 1-30 minutes | 98 mg/dl | Standard Error 5 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | -180 to 0 | 109 mg/dl | Standard Error 9 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 151 to 180 minutes | 107 mg/dl | Standard Error 5 |
| 2X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 31-60 minutes | 98 mg/dl | Standard Error 5 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 61-90 minutes | 118 mg/dl | Standard Error 8 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | -180 to 0 | 120 mg/dl | Standard Error 10 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 1-30 minutes | 110 mg/dl | Standard Error 8 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 31-60 minutes | 113 mg/dl | Standard Error 7 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 91-120 minutes | 117 mg/dl | Standard Error 9 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 121 to 150 minutes | 115 mg/dl | Standard Error 8 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 151 to 180 minutes | 113 mg/dl | Standard Error 8 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 181 to 210 minutes | 112 mg/dl | Standard Error 9 |
| 3X 8mg Oral Insulin Capsules | Plasma Glucose Concentrations | 210 to 240 minutes | 117 mg/dl | Standard Error 10 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucose Concentrations | 1-30 minutes | 115 mg/dl | Standard Error 7 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucose Concentrations | 61-90 minutes | 116 mg/dl | Standard Error 5 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucose Concentrations | 151 to 180 minutes | 120 mg/dl | Standard Error 7 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucose Concentrations | -180 to 0 | 123 mg/dl | Standard Error 8 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucose Concentrations | 210 to 240 minutes | 128 mg/dl | Standard Error 8 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucose Concentrations | 91-120 minutes | 115 mg/dl | Standard Error 5 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucose Concentrations | 31-60 minutes | 116 mg/dl | Standard Error 6 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucose Concentrations | 181 to 210 minutes | 122 mg/dl | Standard Error 8 |
| 1X 16mg Oral Insulin Capsules | Plasma Glucose Concentrations | 121 to 150 minutes | 118 mg/dl | Standard Error 6 |
Secondary
Plasma Insulin Concentrations
Baseline and every 15 minutes during procedures (microIU/mL).
Time frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month
Population: Plasma insulin Concentrations were measured during each procedure in a type 1 DM population Analysis from one subject was not included: Results below threshold of assay
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 165 minutes | 9 microUnits/mL | Standard Deviation 6 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 90 minutes | 9 microUnits/mL | Standard Deviation 4 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 30 minutes | 8 microUnits/mL | Standard Deviation 5 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 45 minutes | 8 microUnits/mL | Standard Deviation 4 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 105 minutes | 9 microUnits/mL | Standard Deviation 6 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 240 minutes | 9 microUnits/mL | Standard Deviation 6 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 150 minutes | 8 microUnits/mL | Standard Deviation 5 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 120 minutes | 9 microUnits/mL | Standard Deviation 6 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 210 minutes | 8 microUnits/mL | Standard Deviation 5 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 135 minutes | 8 microUnits/mL | Standard Deviation 5 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 15 minutes | 9 microUnits/mL | Standard Deviation 4 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 195 minutes | 9 microUnits/mL | Standard Deviation 6 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 60 minutes | 8 microUnits/mL | Standard Deviation 5 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | Baseline | 9 microUnits/mL | Standard Deviation 4 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 180 minutes | 9 microUnits/mL | Standard Deviation 6 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 75 minutes | 8 microUnits/mL | Standard Deviation 5 |
| 2X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 230 minutes | 9 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 150 minutes | 8 microUnits/mL | Standard Deviation 5 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | Baseline | 8 microUnits/mL | Standard Deviation 8 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 15 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 30 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 45 minutes | 7 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 60 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 75 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 90 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 105 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 120 minutes | 8 microUnits/mL | Standard Deviation 5 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 135 minutes | 8 microUnits/mL | Standard Deviation 5 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 165 minutes | 8 microUnits/mL | Standard Deviation 5 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 180 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 195 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 210 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 230 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 3X 8mg Oral Insulin Capsules | Plasma Insulin Concentrations | 240 minutes | 7 microUnits/mL | Standard Deviation 6 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 15 minutes | 7 microUnits/mL | Standard Deviation 6 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 165 minutes | 6 microUnits/mL | Standard Deviation 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 60 minutes | 7 microUnits/mL | Standard Deviation 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 240 minutes | 7 microUnits/mL | Standard Deviation 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 180 minutes | 6 microUnits/mL | Standard Deviation 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 45 minutes | 7 microUnits/mL | Standard Deviation 5 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 230 minutes | 7 microUnits/mL | Standard Deviation 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 195 minutes | 6 microUnits/mL | Standard Deviation 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 30 minutes | 8 microUnits/mL | Standard Deviation 6 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | Baseline | 7 microUnits/mL | Standard Deviation 4 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 120 minutes | 7 microUnits/mL | Standard Deviation 6 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 210 minutes | 6 microUnits/mL | Standard Deviation 5 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 135 minutes | 7 microUnits/mL | Standard Deviation 6 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 105 minutes | 7 microUnits/mL | Standard Deviation 5 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 90 minutes | 7 microUnits/mL | Standard Deviation 5 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 150 minutes | 7 microUnits/mL | Standard Deviation 5 |
| 1X 16mg Oral Insulin Capsules | Plasma Insulin Concentrations | 75 minutes | 7 microUnits/mL | Standard Deviation 5 |