Trial Outcomes & Findings for A Euglycemic Insulin Clamp Study in Type 1 Diabetic Patients With Oral Insulin (ORAMED) (NCT NCT02535715)

NCT ID: NCT02535715

Last Updated: 2019-03-21

Results Overview

Tritiated glucose infusion during procedures (Baseline and every 30 minutes during procedures) Calculated from plasma(mg/kg-minute). Averaged every 30 minutes.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 11 participants
• Primary outcome timeframe: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month
• Results posted on: 2019-03-21

Participant Flow

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.

Participant milestones

Measure	2 x 8mg Oral Insulin Capsules Subject enrolled in study who will be assigned to different interventions for the 3 periods of the study with a 3 day to 4 week interval between the different interventions. For this arm, participants will receive the 2x8mg dose first. 2 x 8mg Oral Insulin Capsules 3 x 8mg Oral Insulin Capsules 1 x 16mg Oral Insulin Capsule	3 x 8mg Oral Insulin Capsules Subject enrolled in study who will be assigned to different interventions for the 3 periods of the study with a 3 day to 4 week interval between the different interventions. For this arm, participants will receive the 3x8mg dose first. 2 x 8mg Oral Insulin Capsules 3 x 8mg Oral Insulin Capsules 1 x 16mg Oral Insulin Capsule	1 X 16mg Oral Insulin Capsule Subject enrolled in study who will be assigned to different interventions for the 3 periods of the study with a 3 day to 4 week interval between the different interventions. For this arm, participants will receive the 1 x 16mg dose first. 2 x 8mg Oral Insulin Capsules 3 x 8mg Oral Insulin Capsules 1 x 16mg Oral Insulin Capsule
Overall Study STARTED	4	4	3
Overall Study COMPLETED	4	4	2
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Measure	2 x 8mg Oral Insulin Capsules Subject enrolled in study who will be assigned to different interventions for the 3 periods of the study with a 3 day to 4 week interval between the different interventions. For this arm, participants will receive the 2x8mg dose first. 2 x 8mg Oral Insulin Capsules 3 x 8mg Oral Insulin Capsules 1 x 16mg Oral Insulin Capsule	3 x 8mg Oral Insulin Capsules Subject enrolled in study who will be assigned to different interventions for the 3 periods of the study with a 3 day to 4 week interval between the different interventions. For this arm, participants will receive the 3x8mg dose first. 2 x 8mg Oral Insulin Capsules 3 x 8mg Oral Insulin Capsules 1 x 16mg Oral Insulin Capsule	1 X 16mg Oral Insulin Capsule Subject enrolled in study who will be assigned to different interventions for the 3 periods of the study with a 3 day to 4 week interval between the different interventions. For this arm, participants will receive the 1 x 16mg dose first. 2 x 8mg Oral Insulin Capsules 3 x 8mg Oral Insulin Capsules 1 x 16mg Oral Insulin Capsule
Overall Study Withdrawal by Subject	0	0	1

Baseline Characteristics

A Euglycemic Insulin Clamp Study in Type 1 Diabetic Patients With Oral Insulin (ORAMED)

Baseline characteristics by cohort

Measure	Overall Study n=11 Participants 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.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	40 years STANDARD_DEVIATION 14 • n=93 Participants
Sex: Female, Male Female	6 Participants n=93 Participants
Sex: Female, Male Male	5 Participants n=93 Participants
Race/Ethnicity, Customized Asian or Pacific Islander	1 Participants n=93 Participants
Race/Ethnicity, Customized Black-non Hispanic	1 Participants n=93 Participants
Race/Ethnicity, Customized Hispanic	3 Participants n=93 Participants
Race/Ethnicity, Customized White non-Hispanic	6 Participants n=93 Participants
Region of Enrollment United States	11 participants n=93 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	2X 8mg Oral Insulin Capsules n=11 Participants ORAMED provided 8 mg oral insulin capsules. Two (2) capsules administered at time 0 of the euglycemic clamp	3X 8mg Oral Insulin Capsules n=11 Participants ORAMED provided 8 mg oral insulin capsules. Three (3) capsules administered at time 0 of the euglycemic clamp	1X 16mg Oral Insulin Capsules n=10 Participants ORAMED provided 16mg oral insulin capsules. One(1) capsule administered at time 0 of the euglycemic clamp
Hepatic Glucose Production (Co-primary Outcome) -180 to 0	2.0 mg/kg-minute Standard Error 0.1	2.0 mg/kg-minute Standard Error 0.1	2.1 mg/kg-minute Standard Error 0.3
Hepatic Glucose Production (Co-primary Outcome) 1-30 minutes	1.8 mg/kg-minute Standard Error 0.2	1.9 mg/kg-minute Standard Error 0.1	2.1 mg/kg-minute Standard Error 0.3
Hepatic Glucose Production (Co-primary Outcome) 31-60 minutes	1.6 mg/kg-minute Standard Error 0.2	1.7 mg/kg-minute Standard Error 0.20	2.1 mg/kg-minute Standard Error 0.4
Hepatic Glucose Production (Co-primary Outcome) 61-90 minutes	1.5 mg/kg-minute Standard Error 0.2	1.6 mg/kg-minute Standard Error 0.1	1.9 mg/kg-minute Standard Error 0.4
Hepatic Glucose Production (Co-primary Outcome) 91-120 minutes	1.6 mg/kg-minute Standard Error 0.2	1.7 mg/kg-minute Standard Error 0.2	1.7 mg/kg-minute Standard Error 0.5
Hepatic Glucose Production (Co-primary Outcome) 121-150 minutes	1.5 mg/kg-minute Standard Error 0.2	1.6 mg/kg-minute Standard Error 0.2	1.6 mg/kg-minute Standard Error 0.5
Hepatic Glucose Production (Co-primary Outcome) 151-180 minutes	1.6 mg/kg-minute Standard Error 0.2	1.6 mg/kg-minute Standard Error 0.2	1.7 mg/kg-minute Standard Error 0.5
Hepatic Glucose Production (Co-primary Outcome) 181-210 minutes	1.5 mg/kg-minute Standard Error 0.2	1.5 mg/kg-minute Standard Error 0.2	1.4 mg/kg-minute Standard Error 0.2
Hepatic Glucose Production (Co-primary Outcome) 211-240	1.4 mg/kg-minute Standard Error 0.2	1.5 mg/kg-minute Standard Error 0.2	1.5 mg/kg-minute Standard Error 0.3

SECONDARY outcome

Timeframe: 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

Baseline and every 15 minutes during procedures (microIU/mL).

Outcome measures

Measure	2X 8mg Oral Insulin Capsules n=11 Participants ORAMED provided 8 mg oral insulin capsules. Two (2) capsules administered at time 0 of the euglycemic clamp	3X 8mg Oral Insulin Capsules n=11 Participants ORAMED provided 8 mg oral insulin capsules. Three (3) capsules administered at time 0 of the euglycemic clamp	1X 16mg Oral Insulin Capsules n=10 Participants ORAMED provided 16mg oral insulin capsules. One(1) capsule administered at time 0 of the euglycemic clamp
Plasma Insulin Concentrations Baseline	9 microUnits/mL Standard Deviation 4	8 microUnits/mL Standard Deviation 8	7 microUnits/mL Standard Deviation 4
Plasma Insulin Concentrations 15 minutes	9 microUnits/mL Standard Deviation 4	8 microUnits/mL Standard Deviation 6	7 microUnits/mL Standard Deviation 6
Plasma Insulin Concentrations 30 minutes	8 microUnits/mL Standard Deviation 5	8 microUnits/mL Standard Deviation 6	8 microUnits/mL Standard Deviation 6
Plasma Insulin Concentrations 45 minutes	8 microUnits/mL Standard Deviation 4	7 microUnits/mL Standard Deviation 6	7 microUnits/mL Standard Deviation 5
Plasma Insulin Concentrations 60 minutes	8 microUnits/mL Standard Deviation 5	8 microUnits/mL Standard Deviation 6	7 microUnits/mL Standard Deviation 4
Plasma Insulin Concentrations 75 minutes	8 microUnits/mL Standard Deviation 5	8 microUnits/mL Standard Deviation 6	7 microUnits/mL Standard Deviation 5
Plasma Insulin Concentrations 90 minutes	9 microUnits/mL Standard Deviation 4	8 microUnits/mL Standard Deviation 6	7 microUnits/mL Standard Deviation 5
Plasma Insulin Concentrations 105 minutes	9 microUnits/mL Standard Deviation 6	8 microUnits/mL Standard Deviation 6	7 microUnits/mL Standard Deviation 5
Plasma Insulin Concentrations 120 minutes	9 microUnits/mL Standard Deviation 6	8 microUnits/mL Standard Deviation 5	7 microUnits/mL Standard Deviation 6
Plasma Insulin Concentrations 135 minutes	8 microUnits/mL Standard Deviation 5	8 microUnits/mL Standard Deviation 5	7 microUnits/mL Standard Deviation 6
Plasma Insulin Concentrations 150 minutes	8 microUnits/mL Standard Deviation 5	8 microUnits/mL Standard Deviation 5	7 microUnits/mL Standard Deviation 5
Plasma Insulin Concentrations 165 minutes	9 microUnits/mL Standard Deviation 6	8 microUnits/mL Standard Deviation 5	6 microUnits/mL Standard Deviation 4
Plasma Insulin Concentrations 180 minutes	9 microUnits/mL Standard Deviation 6	8 microUnits/mL Standard Deviation 6	6 microUnits/mL Standard Deviation 4
Plasma Insulin Concentrations 195 minutes	9 microUnits/mL Standard Deviation 6	8 microUnits/mL Standard Deviation 6	6 microUnits/mL Standard Deviation 4
Plasma Insulin Concentrations 210 minutes	8 microUnits/mL Standard Deviation 5	8 microUnits/mL Standard Deviation 6	6 microUnits/mL Standard Deviation 5
Plasma Insulin Concentrations 230 minutes	9 microUnits/mL Standard Deviation 6	8 microUnits/mL Standard Deviation 6	7 microUnits/mL Standard Deviation 4
Plasma Insulin Concentrations 240 minutes	9 microUnits/mL Standard Deviation 6	7 microUnits/mL Standard Deviation 6	7 microUnits/mL Standard Deviation 4

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	2X 8mg Oral Insulin Capsules n=10 Participants ORAMED provided 8 mg oral insulin capsules. Two (2) capsules administered at time 0 of the euglycemic clamp	3X 8mg Oral Insulin Capsules n=10 Participants ORAMED provided 8 mg oral insulin capsules. Three (3) capsules administered at time 0 of the euglycemic clamp	1X 16mg Oral Insulin Capsules n=10 Participants ORAMED provided 16mg oral insulin capsules. One(1) capsule administered at time 0 of the euglycemic clamp
Plasma Glucose Concentrations -180 to 0	109 mg/dl Standard Error 9	120 mg/dl Standard Error 10	123 mg/dl Standard Error 8
Plasma Glucose Concentrations 1-30 minutes	98 mg/dl Standard Error 5	110 mg/dl Standard Error 8	115 mg/dl Standard Error 7
Plasma Glucose Concentrations 31-60 minutes	98 mg/dl Standard Error 5	113 mg/dl Standard Error 7	116 mg/dl Standard Error 6
Plasma Glucose Concentrations 61-90 minutes	100 mg/dl Standard Error 6	118 mg/dl Standard Error 8	116 mg/dl Standard Error 5
Plasma Glucose Concentrations 91-120 minutes	103 mg/dl Standard Error 5	117 mg/dl Standard Error 9	115 mg/dl Standard Error 5
Plasma Glucose Concentrations 121 to 150 minutes	105 mg/dl Standard Error 5	115 mg/dl Standard Error 8	118 mg/dl Standard Error 6
Plasma Glucose Concentrations 151 to 180 minutes	107 mg/dl Standard Error 5	113 mg/dl Standard Error 8	120 mg/dl Standard Error 7
Plasma Glucose Concentrations 181 to 210 minutes	110 mg/dl Standard Error 6	112 mg/dl Standard Error 9	122 mg/dl Standard Error 8
Plasma Glucose Concentrations 210 to 240 minutes	111 mg/dl Standard Error 7	117 mg/dl Standard Error 10	128 mg/dl Standard Error 8

SECONDARY outcome

Timeframe: 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.

Measured at baseline and every 30 minutes during the procedures (pg/mL)

Outcome measures

Measure	2X 8mg Oral Insulin Capsules n=11 Participants ORAMED provided 8 mg oral insulin capsules. Two (2) capsules administered at time 0 of the euglycemic clamp	3X 8mg Oral Insulin Capsules n=11 Participants ORAMED provided 8 mg oral insulin capsules. Three (3) capsules administered at time 0 of the euglycemic clamp	1X 16mg Oral Insulin Capsules n=10 Participants ORAMED provided 16mg oral insulin capsules. One(1) capsule administered at time 0 of the euglycemic clamp
Plasma Glucagon Concentrations -180 to 0 minutes	29 pg/mL Standard Error 4	37 pg/mL Standard Error 4	37 pg/mL Standard Error 4
Plasma Glucagon Concentrations 1-30 minutes	29 pg/mL Standard Error 4	38 pg/mL Standard Error 5	36 pg/mL Standard Error 4
Plasma Glucagon Concentrations 31-60 minutes	27 pg/mL Standard Error 3	37 pg/mL Standard Error 4	34 pg/mL Standard Error 5
Plasma Glucagon Concentrations 61-90 minutes	29 pg/mL Standard Error 3	36 pg/mL Standard Error 4	34 pg/mL Standard Error 5
Plasma Glucagon Concentrations 91-120 minutes	28 pg/mL Standard Error 4	34 pg/mL Standard Error 4	33 pg/mL Standard Error 4
Plasma Glucagon Concentrations 121-150 minutes	26 pg/mL Standard Error 3	35 pg/mL Standard Error 4	34 pg/mL Standard Error 4
Plasma Glucagon Concentrations 151-180 minutes	26 pg/mL Standard Error 4	35 pg/mL Standard Error 4	33 pg/mL Standard Error 4
Plasma Glucagon Concentrations 181 to 210 minutes	23 pg/mL Standard Error 3	35 pg/mL Standard Error 4	31 pg/mL Standard Error 4
Plasma Glucagon Concentrations 211-240 minutes	24 pg/mL Standard Error 3	36 pg/mL Standard Error 4	32 pg/mL Standard Error 4

SECONDARY outcome

Timeframe: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month

Population: Wako Calorometric

Measured at baseline and every 30 minutes during the procedures (micro mol/L)

Outcome measures

Measure	2X 8mg Oral Insulin Capsules n=10 Participants ORAMED provided 8 mg oral insulin capsules. Two (2) capsules administered at time 0 of the euglycemic clamp	3X 8mg Oral Insulin Capsules n=10 Participants ORAMED provided 8 mg oral insulin capsules. Three (3) capsules administered at time 0 of the euglycemic clamp	1X 16mg Oral Insulin Capsules n=10 Participants ORAMED provided 16mg oral insulin capsules. One(1) capsule administered at time 0 of the euglycemic clamp
Plasma Free Fatty Acid Concentrations Baseline	380 mmol/L Standard Error 68	402 mmol/L Standard Error 80	410 mmol/L Standard Error 87
Plasma Free Fatty Acid Concentrations 1-30 minutes	408 mmol/L Standard Error 76	465 mmol/L Standard Error 81	467 mmol/L Standard Error 69
Plasma Free Fatty Acid Concentrations 31-60 minutes	463 mmol/L Standard Error 78	533 mmol/L Standard Error 96	448 mmol/L Standard Error 61
Plasma Free Fatty Acid Concentrations 61-90 minutes	472 mmol/L Standard Error 74	545 mmol/L Standard Error 102	489 mmol/L Standard Error 63
Plasma Free Fatty Acid Concentrations 91-120 minutes	495 mmol/L Standard Error 84	473 mmol/L Standard Error 94	506 mmol/L Standard Error 56
Plasma Free Fatty Acid Concentrations 121-150 minutes	528 mmol/L Standard Error 74	501 mmol/L Standard Error 97	509 mmol/L Standard Error 54
Plasma Free Fatty Acid Concentrations 151-180 minutes	547 mmol/L Standard Error 80	486 mmol/L Standard Error 95	545 mmol/L Standard Error 53
Plasma Free Fatty Acid Concentrations 181-210 minutes	523 mmol/L Standard Error 75	485 mmol/L Standard Error 97	533 mmol/L Standard Error 63
Plasma Free Fatty Acid Concentrations 211-240 minutes	490 mmol/L Standard Error 69	486 mmol/L Standard Error 95	538 mmol/L Standard Error 74

Adverse Events

2X 8mg Capsules

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

3X 8mg Oral Insulin Capsules

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

1X 16mg Capsules

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	2X 8mg Capsules n=11 participants at risk Adverse event reporting for subjects during the 2X 8mg dosing regimen	3X 8mg Oral Insulin Capsules n=11 participants at risk Adverse event reporting for subjects during the 3X 8mg dosing regimen	1X 16mg Capsules n=10 participants at risk Adverse event reporting for subjects during the 1X 16mg dosing regimen
Endocrine disorders Hypoglycemia	0.00% 0/11 • Adverse Events were collected over period of participation of each subject: From signing of informed consent, including between procedures, until conclusion of 3rd procedure. Subjects were instructed to call us if any adverse events after this timeframe.	9.1% 1/11 • Number of events 1 • Adverse Events were collected over period of participation of each subject: From signing of informed consent, including between procedures, until conclusion of 3rd procedure. Subjects were instructed to call us if any adverse events after this timeframe.	0.00% 0/10 • Adverse Events were collected over period of participation of each subject: From signing of informed consent, including between procedures, until conclusion of 3rd procedure. Subjects were instructed to call us if any adverse events after this timeframe.

Additional Information

Curtis Triplitt, PharmD

University of Texas Health San Antonio

Phone: 210-358-7228

Email: triplitt@uthscsa.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place