Trial Outcomes & Findings for A Study to Compare ORMD-0801 Once Daily to ORMD-0801 Three Times Daily in Subjects With Type 1 Diabetes (NCT NCT04150107)
NCT ID: NCT04150107
Last Updated: 2022-06-02
Results Overview
The least squares means difference of basal exogenous insulin between treatment A and placebo and treatment B and placebo, utilized over the final ten (10) days of each treatment period
COMPLETED
PHASE2
30 participants
Combined Final ten days of each treatment period. Period1 (days -8 to 1)Period 2 (days 19 to 28) ,and Period 3 (days 47 to 56)
2022-06-02
Participant Flow
This is a crossover study with one crossover point. There are three periods in this study: Period 1: all patients consented receive placebo (run-in period). Period 2: all patients are randomized to receive either Treatment A or Treatment B. Period 3: Crossover point. Patients receiving Treatment A in period 2 now receive Treatment B in period 3, and patients receiving Treatment B in period 2 now receive Treatment A in period 3.
Participant milestones
| Measure |
Placebo Followed by Treatment A Followed by Treatment B
Treatment administered in the following order:
1. Placebo Fish oil capsule
2. Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801 ORMD-0801: Oral Insulin Capsules
3. Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals ORMD-0801: Oral Insulin Capsules
|
Placebo Followed by Treatment B Followed by Treatment A
Treatment administered in the following order:
1. Placebo Fish oil capsule
2. Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals ORMD-0801: Oral Insulin Capsules
3. Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801 ORMD-0801: Oral Insulin Capsules
|
|---|---|---|
|
Period 1- Placebo run-in (All Patients)
STARTED
|
14
|
16
|
|
Period 1- Placebo run-in (All Patients)
COMPLETED
|
14
|
16
|
|
Period 1- Placebo run-in (All Patients)
NOT COMPLETED
|
0
|
0
|
|
Period 2- Either Treatment A or B
STARTED
|
14
|
16
|
|
Period 2- Either Treatment A or B
COMPLETED
|
14
|
16
|
|
Period 2- Either Treatment A or B
NOT COMPLETED
|
0
|
0
|
|
Period 3 Crossover-Treatment B or A
STARTED
|
14
|
16
|
|
Period 3 Crossover-Treatment B or A
COMPLETED
|
12
|
15
|
|
Period 3 Crossover-Treatment B or A
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Placebo Followed by Treatment A Followed by Treatment B
Treatment administered in the following order:
1. Placebo Fish oil capsule
2. Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801 ORMD-0801: Oral Insulin Capsules
3. Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals ORMD-0801: Oral Insulin Capsules
|
Placebo Followed by Treatment B Followed by Treatment A
Treatment administered in the following order:
1. Placebo Fish oil capsule
2. Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals ORMD-0801: Oral Insulin Capsules
3. Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801 ORMD-0801: Oral Insulin Capsules
|
|---|---|---|
|
Period 3 Crossover-Treatment B or A
Adverse Event
|
2
|
0
|
|
Period 3 Crossover-Treatment B or A
Patient non-compliance
|
0
|
1
|
Baseline Characteristics
This is a crossover study. All patients were administered placebo at baseline.
Baseline characteristics by cohort
| Measure |
Placebo Followed by Treatment A Followed by Treatment B
n=14 Participants
Treatment administerd in the following order:
1. Placebo, standard of care Fish oil capsules
2. Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801 ORMD-0801: Oral Insulin Capsules
3. Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals ORMD-0801: Oral Insulin Capsules
|
Placebo Followed by Treatment B Followed by Treatment A
n=16 Participants
Treatment administerd in the following order:
1. Placebo, standard of care Fish oil capsules
2. Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals ORMD-0801: Oral Insulin Capsules
3. Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801 ORMD-0801: Oral Insulin Capsules
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.79285714 years
STANDARD_DEVIATION 12.67793142 • n=5 Participants • This is a crossover study. All patients were administered placebo at baseline.
|
42.88125 years
STANDARD_DEVIATION 16.04131614 • n=7 Participants • This is a crossover study. All patients were administered placebo at baseline.
|
43.30667 years
STANDARD_DEVIATION 12.22325 • n=5 Participants • This is a crossover study. All patients were administered placebo at baseline.
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 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
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
28 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
|
|
Pre-dose Hb1Ac(%)
|
7.735714286 percent
STANDARD_DEVIATION 0.734435569 • n=5 Participants
|
7.6125 percent
STANDARD_DEVIATION 0.848429922 • n=7 Participants
|
7.67 percent
STANDARD_DEVIATION 0.786 • n=5 Participants
|
PRIMARY outcome
Timeframe: Combined Final ten days of each treatment period. Period1 (days -8 to 1)Period 2 (days 19 to 28) ,and Period 3 (days 47 to 56)Population: Information collected at the day 28 visits (Day 28 and Day 56) will be analyzed using an Analysis of Covariance model with subject as a random effect.
The least squares means difference of basal exogenous insulin between treatment A and placebo and treatment B and placebo, utilized over the final ten (10) days of each treatment period
Outcome measures
| Measure |
Baseline
n=30 Participants
Placebo (Fish-Oil Capsule)
|
Treatment A
n=27 Participants
Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801
ORMD-0801: Oral Insulin Capsules
|
Treatment B
n=27 Participants
Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals
ORMD-0801: Oral Insulin Capsules
|
|---|---|---|---|
|
Average Exogenous Basal Insulin Compared to Baseline (Placebo)
Least Squares Mean Baseline, Treatment A, Treatment B
|
27.28 mg/dL
Standard Error 2.489
|
25.84 mg/dL
Standard Error 2.486
|
27.32 mg/dL
Standard Error 2.492
|
|
Average Exogenous Basal Insulin Compared to Baseline (Placebo)
Least Squares Mean Difference Treatment A minus Baseline or Treatment B minus Baseline
|
NA mg/dL
Standard Error NA
Calculation not applicable to this Arm/Group
|
-1.43 mg/dL
Standard Error 0.381
|
0.04 mg/dL
Standard Error 0.421
|
PRIMARY outcome
Timeframe: Combined Final ten days of treatment per treatment period (Days -8 to 1, Days 19 to 28, and Days 47 to 56)Population: Safety Population
The amount of exogenous bolus insulin utilized over the final ten (10) days of each treatment period measured in mg/dL
Outcome measures
| Measure |
Baseline
n=30 Participants
Placebo (Fish-Oil Capsule)
|
Treatment A
n=27 Participants
Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801
ORMD-0801: Oral Insulin Capsules
|
Treatment B
n=27 Participants
Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals
ORMD-0801: Oral Insulin Capsules
|
|---|---|---|---|
|
Average Exogenous Bolus Insulin Compared to Baseline (Placebo)
Least Squares Means Baseline, Treatment A, Treatment B
|
20.63 mg/dL
Standard Error 2.033
|
20.77 mg/dL
Standard Error 2.045
|
20.54 mg/dL
Standard Error 2.049
|
|
Average Exogenous Bolus Insulin Compared to Baseline (Placebo)
Least Squares Means Difference Treatment A minus Baseline, Treatmen B minus Baseline
|
NA mg/dL
Standard Error NA
Calculation not applicable to this Arm/Group.
|
0.14 mg/dL
Standard Error 0.634
|
-0.09 mg/dL
Standard Error 0.645
|
PRIMARY outcome
Timeframe: Combined Final ten days of treatment , day -8 to 1 (Period 1) Days 19 to 28 (Period 2), Days 47 to 56 (Period 3)Population: Safety Population The number of participants anylized is based on the the number of participants that completed at least 80% of the Continuous Glucose Montioring measurements. Participants that did not meet this criterion are not inclued in this analysis.
The Least Squares Mean Difeerence ( (mg/dL) of total exogenous insulin (the sum of basal + bolus exogenous insulin) over the final ten (10) days of treatment.
Outcome measures
| Measure |
Baseline
n=29 Participants
Placebo (Fish-Oil Capsule)
|
Treatment A
n=27 Participants
Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801
ORMD-0801: Oral Insulin Capsules
|
Treatment B
n=27 Participants
Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals
ORMD-0801: Oral Insulin Capsules
|
|---|---|---|---|
|
Average Exogenous Total Insulin Compared to Baseline
Least Squares Mean Difference Treatment A minus Baseline and Treatment B minus Baseline
|
NA mg/dL
Standard Error NA
Calculation not applicable to this Arm/Group.
|
-0.127 mg/dL
Standard Error 0.758
|
-0.04 mg/dL
Standard Error 0.798
|
|
Average Exogenous Total Insulin Compared to Baseline
Least Squares Mean
|
47.92 mg/dL
Standard Error 3.395
|
46.64 mg/dL
Standard Error 3.397
|
47.88 mg/dL
Standard Error 3.406
|
SECONDARY outcome
Timeframe: Combined Study days -8 to 1 (Period 1) Days 19 to 28 (Period 2), and days 47 to 56 (Period 3)Population: Safety Population. The number of participants anylized is based on the the number of participants that completed at least 80% of the Continuous Glucose Montioring measurements. Participants that did not meet this criterion are not inclued in this analysis.
Least Squares Mean Difference from Baseline of Daytime Average Mean Glucose over the final ten (10) days of each treatment and each treatment period as measured by CGM.
Outcome measures
| Measure |
Baseline
n=30 Participants
Placebo (Fish-Oil Capsule)
|
Treatment A
n=26 Participants
Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801
ORMD-0801: Oral Insulin Capsules
|
Treatment B
n=26 Participants
Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals
ORMD-0801: Oral Insulin Capsules
|
|---|---|---|---|
|
Daytime Average Mean Glucose Compared to Baseline
Least Sqaures Mean Baseline, Treatment A, Treatment B
|
168.72 mg/dL
Standard Error 5.825
|
174.84 mg/dL
Standard Error 5.957
|
169.75 mg/dL
Standard Error 5.930
|
|
Daytime Average Mean Glucose Compared to Baseline
Least Squares Mean Difference between each treatment and placebo
|
NA mg/dL
Standard Error NA
Calculation not applicable to this Arm/Group.
|
6.12 mg/dL
Standard Error 3.966
|
1.02 mg/dL
Standard Error 3.889
|
SECONDARY outcome
Timeframe: Study Days -8 to 1 (Period 1), Days 19-28 (Period 2), and Days 47-56 (Period 3)Population: Safety Population. The number of participants anylized is based on the the number of participants that completed at least 80% of the Continuous Glucose Montioring measurements. Participants that did not meet this criterion are not inclued in this analysis.
Least Squares Mean Continuous Glucose Monitor (CGM) Glucose Coefficient of Variation measured over daytime hours, compared to Baseline
Outcome measures
| Measure |
Baseline
n=30 Participants
Placebo (Fish-Oil Capsule)
|
Treatment A
n=26 Participants
Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801
ORMD-0801: Oral Insulin Capsules
|
Treatment B
n=26 Participants
Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals
ORMD-0801: Oral Insulin Capsules
|
|---|---|---|---|
|
Daytime Glucose Coefficient of Variation Compared to Baseline
Least Squares Mean
|
45.287 percent (%)
Standard Error 2.3191
|
46.550 percent (%)
Standard Error 2.3073
|
44.996 percent (%)
Standard Error 2.2847
|
|
Daytime Glucose Coefficient of Variation Compared to Baseline
Least Squares Mean Differece between each treatment and placebo.
|
NA percent (%)
Standard Error NA
Calculation not applicable to this Arm/Group.
|
1.64 percent (%)
Standard Error 1.949
|
-0.291 percent (%)
Standard Error 1.9064
|
SECONDARY outcome
Timeframe: Combined Study Days -8 to 1 (Period 1), Days 19-28 (Period 2), and Days 47-56 (Period 3)Population: Safety Population. The number of participants anylized is based on the the number of participants that completed at least 80% of the Continuous Glucose Montioring measurements. Participants that did not meet this criterion are not inclued in this analysis
Least Squares Mean Daytime Low Blood Glucose Index (LBGI) measured over the last ten (10) days of the treatment period, compared to Baseline LBGI is a clinical scale that indicates the probability for hypoglycemia. Blood Glucose Variability is an important measure because it provides additional clarification for HbA1c value. The risk of hypglycemic events and the LBGI scale is defined as follows: Minimal Risk ( LBGI \< 1.1) Low Risk ( 1.1 \< LBGI \< 2.5) Moderate Risk (2.5 \< LBGI \< 5), HIgh Risk ( LBGI \> 5)
Outcome measures
| Measure |
Baseline
n=30 Participants
Placebo (Fish-Oil Capsule)
|
Treatment A
n=26 Participants
Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801
ORMD-0801: Oral Insulin Capsules
|
Treatment B
n=26 Participants
Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals
ORMD-0801: Oral Insulin Capsules
|
|---|---|---|---|
|
Daytime Low Blood Glucose Index (LBGI) Compared to Baseline
Least Squares Mean Daytime Low Blood Glucose Index (LBGI) for Baseline,
|
1.65 units on a scale
Standard Error 0.284
|
1.53 units on a scale
Standard Error 0.282
|
1.65 units on a scale
Standard Error 0.288
|
|
Daytime Low Blood Glucose Index (LBGI) Compared to Baseline
Least Squares Mean Difference between Treatment A and Placebo, Treatment B and Placebo.
|
NA units on a scale
Standard Error NA
Calculation not applicable to this Arm/Group.
|
-0.12 units on a scale
Standard Error 0.294
|
0.00 units on a scale
Standard Error 0.297
|
Adverse Events
Placebo
Treatment A ORMD-0801
Treatment B ORMD-0801
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=30 participants at risk
Placebo - Fish Oil
|
Treatment A ORMD-0801
n=30 participants at risk
Treatment A is 24 mg (16 mg + 8 mg capsules) Once Daily (QD) at Bedtime of ORMD-0801
ORMD-0801 Treatment A: Treatment A: 24 mg (16 mg capsule + 8 mg capsule) Once Daily (QD) at bedtime
|
Treatment B ORMD-0801
n=30 participants at risk
Treatment B is 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals
ORMD-0801 Treatment B: Treatment B: 8 mg (8 mg capsule) three times a day (TID) 45-90 minutes before meals
|
|---|---|---|---|
|
Infections and infestations
Nasopharangitis
|
0.00%
0/30 • Sixty-six (66) days
|
0.00%
0/30 • Sixty-six (66) days
|
3.3%
1/30 • Number of events 1 • Sixty-six (66) days
|
|
Infections and infestations
OTITIS EXTERNA
|
0.00%
0/30 • Sixty-six (66) days
|
0.00%
0/30 • Sixty-six (66) days
|
3.3%
1/30 • Number of events 1 • Sixty-six (66) days
|
|
Immune system disorders
Sinusitis
|
0.00%
0/30 • Sixty-six (66) days
|
0.00%
0/30 • Sixty-six (66) days
|
3.3%
1/30 • Number of events 1 • Sixty-six (66) days
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
0.00%
0/30 • Sixty-six (66) days
|
3.3%
1/30 • Number of events 1 • Sixty-six (66) days
|
3.3%
1/30 • Number of events 1 • Sixty-six (66) days
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/30 • Sixty-six (66) days
|
3.3%
1/30 • Number of events 1 • Sixty-six (66) days
|
3.3%
1/30 • Number of events 1 • Sixty-six (66) days
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/30 • Sixty-six (66) days
|
3.3%
1/30 • Number of events 1 • Sixty-six (66) days
|
3.3%
1/30 • Number of events 1 • Sixty-six (66) days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/30 • Sixty-six (66) days
|
6.7%
2/30 • Number of events 2 • Sixty-six (66) days
|
0.00%
0/30 • Sixty-six (66) days
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/30 • Sixty-six (66) days
|
3.3%
1/30 • Number of events 1 • Sixty-six (66) days
|
0.00%
0/30 • Sixty-six (66) days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60