Trial Outcomes & Findings for A Study to Evaluate the Effect of ORMD-0801 in Patients With Type 2 Diabetes Mellitus (NCT NCT04564846)

Last Updated: 2024-05-07

Results Overview

The endogenous glucose production in ORMD-0801 and placebo measured by the glucose with tracer attached using AUC(0-16) as the primary parameter. The intravenous infusion of \[6,6-2H2\]-glucose tracer is administered following administraiton of either placebo or intervention. The pharmacokinetic time points are basline (pre dose), 0.75 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, 4 hr, 5 hr, 6 hr, 7 hr, 8 hr, 9 hr, 10 hr, 11 hr, 12 hr, 13 hr, 14 hr, 15 hr, 16 hr post-dose.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

Day 28 (1 day)

Results posted on

2024-05-07

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Placebo: Placebo capsule (Fish Oil)	ORMD-0801 Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. ORMD-0801: 8 mg capsules of ORMD-0801 (Oral Insulin)
Overall Study STARTED	25	24
Overall Study COMPLETED	21	20
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Placebo: Placebo capsule (Fish Oil)	ORMD-0801 Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. ORMD-0801: 8 mg capsules of ORMD-0801 (Oral Insulin)
Overall Study Withdrawal by Subject	2	1
Overall Study Physician Decision	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Principal Investigator requested that the patient withdraw from the study	1	1
Overall Study Subject non-compliance	1	0

Baseline Characteristics

A Study to Evaluate the Effect of ORMD-0801 in Patients With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=25 Participants Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Placebo: Placebo capsule (Fish Oil)	ORMD-0801 n=24 Participants Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. ORMD-0801: 8 mg capsules of ORMD-0801 (Oral Insulin)	Total n=49 Participants Total of all reporting groups
Age, Continuous	60.19 Years STANDARD_DEVIATION 6.497 • n=5 Participants	58.68 Years STANDARD_DEVIATION 6.904 • n=7 Participants	59.45 Years STANDARD_DEVIATION 6.742 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	14 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	15 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants	9 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants	18 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Childbearing Status Not Applicable	18 Participants n=5 Participants	14 Participants n=7 Participants	32 Participants n=5 Participants
Childbearing Status Of Childbearing Potential	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Childbearing Status Post Hysterectomy	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Childbearing Status Surgically Sterilized	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Childbearing Status At Least one year Post-Menopausal	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Height	170.7 cm STANDARD_DEVIATION 9.96 • n=5 Participants	170.3 cm STANDARD_DEVIATION 11.50 • n=7 Participants	170.5 cm STANDARD_DEVIATION 10.74 • n=5 Participants
Weight	88.09 Kg STANDARD_DEVIATION 14.635 • n=5 Participants	88.80 Kg STANDARD_DEVIATION 16.546 • n=7 Participants	88.438 Kg STANDARD_DEVIATION 15.604 • n=5 Participants
Body Mass Index (BMI)	30.124 Kg/m^2 STANDARD_DEVIATION 3.5803 • n=5 Participants	30.563 Kg/m^2 STANDARD_DEVIATION 3.7834 • n=7 Participants	30.339 Kg/m^2 STANDARD_DEVIATION 3.6877 • n=5 Participants

PRIMARY outcome

Timeframe: Day 28 (1 day)

Population: modified intend-to-treat (mITT) population. mITT consists of all subjects that started on Day 28. All 22 mITT placebo subjects came in for Study Day 28. One subject discontinued after the standard blood tests, prior to the pK measurements due to Non-Compliance or Lack of Cooperation. Thus, the sample size on Day 28 for AUC(0-16) is 21, and for the standard blood tests is 22. The 21 subjects that completed Visit 3 (days 28 + 29) were included in this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Placebo: Placebo capsule (Fish Oil)	ORMD-0801 n=20 Participants Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. ORMD-0801: 8 mg capsules of ORMD-0801 (Oral Insulin)
Area Under the Curve (AUC(0-16)) of Endogenous Glucose Production	3436.8 mg*hr/dL Standard Deviation 922.89	3139.3 mg*hr/dL Standard Deviation 830.29

SECONDARY outcome

Timeframe: baseline to Day 29 of the treatment period.

Population: modified intent-to-treat population (mITT). The mITT population consists of all subjects that started the Day 28 - 16 hour fast and corresponding measurements. All 22 placebo subjects in the mITT population came in for Study Day 28 and started the fast. One subject discontinued prior to the Day 29 measurements due to Non-Compliance or Lack of Cooperation. This is why the Sample Size for Day 28 (and Baseline) is 22 while the Sample Size for Day 29 is 21.

Mean Changes of HbA1c measured in percentage of glycated hemoglobin

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Placebo: Placebo capsule (Fish Oil)	ORMD-0801 n=20 Participants Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. ORMD-0801: 8 mg capsules of ORMD-0801 (Oral Insulin)
Mean Changes in HbA1c Baseline HbA1c	9.20 percentage of glycated hemoglobin Standard Deviation 1.214	8.51 percentage of glycated hemoglobin Standard Deviation 1.401
Mean Changes in HbA1c Day 29 HbA1c	9.19 percentage of glycated hemoglobin Standard Deviation 1.196	8.67 percentage of glycated hemoglobin Standard Deviation 1.319
Mean Changes in HbA1c Difference of HbA1c between baseline and Day 29	0.08 percentage of glycated hemoglobin Standard Deviation 0.452	0.15 percentage of glycated hemoglobin Standard Deviation 0.637

SECONDARY outcome

Timeframe: Day 28

AUC(0-16) measured in umol\*hr/L with blood draws at baseline ( time "0", prior to drug administration), then 45 min, 90 min, 120 min, 150 min, 3-16 hours in one-hour intervals post intervention plus tracer administration via intravenous infusion of \[6,6-2H2\]-glucose tracer. The AUC measured is AUC(0-16) where "0-16" is 0 pre-dose, 0.75 hr. 1.5 hrs, 2 hrs. 2.5 hrs, 3 hrs, 4 hrs, 5 hrs, 6 hrs, 7 hrs, 8 hrs, 9 hrs, 10 hrs, 11 hrs, 12 hrs, 13 hrs, 14 hrs, 15 hrs, 16 hrs. post dose.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Placebo: Placebo capsule (Fish Oil)	ORMD-0801 n=20 Participants Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. ORMD-0801: 8 mg capsules of ORMD-0801 (Oral Insulin)
Area Under the Curve AUC(0-16) of Metabolite Beta-hydroxybutyrate	3435.8 umol*hr/L Standard Deviation 3093.36	2009.7 umol*hr/L Standard Deviation 1659.04

SECONDARY outcome

Timeframe: Day 28 (one day)

The Area Under the Cuve (AUC) measured from baseline (prior to placebo, intervention, and tracer infusion) to sixteen hours post treatment andministration and tracer infusion administration. The tracer is \[6,6-2H2\]-glucose tracer using AUC(0-16). Pharmacokinetic time points are: Baseline (0 hr, pre-dose), then 0.75 hr, 1.5 hrs, 2 hrs, 2.5 hrs., 3 hrs., 4 hrs, 5 hrs, 6 hrs, 7hrs, 8 hrs, 9 hrs, 10 hrs, 11 hrs 12 hrs, 13 hrs, 14 hrs, 15 hrs, 16 hrs (post dose).

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Placebo: Placebo capsule (Fish Oil)	ORMD-0801 n=20 Participants Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. ORMD-0801: 8 mg capsules of ORMD-0801 (Oral Insulin)
Area Under the Curve (AUC) of Insulin	324.8 uU*hr/mL Standard Deviation 147.25	425.1 uU*hr/mL Standard Deviation 274.61

SECONDARY outcome

Timeframe: Day 28 (one day)

AUC measured from Baseline (prior to administration of placebo orintervention and to tracer infusion. The tracer is \[6,6-2H2\]-glucose tracer using AUC(0-16). Pharmacokinetic time points are: Baseline (0 hr, pre-dose), then 0.75 hr, 1.5 hrs, 2 hrs, 2.5 hrs., 3 hrs., 4 hrs, 5 hrs, 6 hrs, 7hrs, 8 hrs, 9 hrs, 10 hrs, 11 hrs 12 hrs, 13 hrs, 14 hrs, 15 hrs, 16 hrs (post dose).

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Placebo: Placebo capsule (Fish Oil)	ORMD-0801 n=20 Participants Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. ORMD-0801: 8 mg capsules of ORMD-0801 (Oral Insulin)
Area Under the Curve (AUC) of Free Fatty Acids (FFA)	7327.2 uEq*hr/L Standard Deviation 1820.31	7051.4 uEq*hr/L Standard Deviation 1788.71

SECONDARY outcome

Timeframe: baseline to Day 29 of the treatment period.

Mean changes in plasma glucose levels measured in mg/dL. In this outcome measure, the change from baseline of mean plasma glucose for the placebo arm is calculated as: Mean Plasma Glucose (Day 29, 21 subjects) - Mean Plasma Glucose (Baseline, 21 subjects). The Baseline Mean Plasma Glucose based on 21 subjects is 192.7 mg/dL. Therefore, 192.7 mg/dL - 212.3 mg/dL = -19.6 mg./dL

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Placebo: Placebo capsule (Fish Oil)	ORMD-0801 n=20 Participants Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. ORMD-0801: 8 mg capsules of ORMD-0801 (Oral Insulin)
Mean Changes Plasma Glucose Levels Plasma Glucose at Baseline	216.4 mg/dL Standard Deviation 55.37	187.5 mg/dL Standard Deviation 48.6
Mean Changes Plasma Glucose Levels Plasma Glucose at Day 29	192.7 mg/dL Standard Deviation 51.62	167.9 mg/dL Standard Deviation 48.58
Mean Changes Plasma Glucose Levels Change in Plasma Glucose from Baseline	-19.6 mg/dL Standard Deviation 46.61	-19.6 mg/dL Standard Deviation 39.68

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

ORMD-0801

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=25 participants at risk Subjects will be administered a single capsule of placebo( fish oil); placebo will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. Placebo: Placebo capsule (Fish Oil)	ORMD-0801 n=24 participants at risk Subjects will be administered a single 8mg capsule of ORMD-0801; study medication will be dispensed and subjects will dose twice a day, once in the morning prior to breakfast and once at night prior to bedtime. ORMD-0801: 8 mg capsules of ORMD-0801 (Oral Insulin)
Gastrointestinal disorders Gastrointestinal disorders	0.00% 0/25 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.	4.2% 1/24 • Number of events 1 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.
Gastrointestinal disorders Abdominal pain	0.00% 0/25 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.	4.2% 1/24 • Number of events 1 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.
Psychiatric disorders Anxiety	4.0% 1/25 • Number of events 1 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.	0.00% 0/24 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/25 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.	4.2% 1/24 • Number of events 1 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/25 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.	4.2% 1/24 • Number of events 1 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.
Psychiatric disorders Disorientation	4.0% 1/25 • Number of events 1 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.	0.00% 0/24 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.
Nervous system disorders Headache	8.0% 2/25 • Number of events 2 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.	12.5% 3/24 • Number of events 3 • Baseline (day 0) until discharge/end-of-study day (day 29) The severity of each AE will be graded according to the NCI CTCAE, version 4.03.

Additional Information

Chief Scientific Officer

Oramed, Ltd.

Phone: +97225660001

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60