Trial Outcomes & Findings for Acute Effect of HP-211 (Axulin) on Blood Glucose and Serum Insulin Responses in Healthy Lean and Overweight Humans (NCT NCT03135015)
NCT ID: NCT03135015
Last Updated: 2020-04-20
Results Overview
Percentage change in the incremental area under the glucose response curve (AUC) after 75g glucose for capsules and tablets containing Axulin powder relative to the water control. Incremental AUC is the AUC below the curve above the fasting level; area below fasting is ignored. Percentage change will be calculated as 100 x (A-P)/P where A and P are the mean AUC's after Axulin and water control treatments, respectively. The blinded AUC results for the 6 treatments will be subjected to repeated measures analysis of variance (ANOVA) examining for the main effects of treatment and participant-group, and treatment\*group interaction. After demonstration of significant heterogeneity among the 6 coded treatments, differences between individual means will be assessed using Tukey's test to adjust for multiple comparisons. The code will be broken after this analysis has been done. The percentage changes will be considered to be significant if the difference in mean AUC is significant.
COMPLETED
PHASE1
22 participants
0, 15, 30, 45, 60, 90, and 120 minutes post-dose
2020-04-20
Participant Flow
Participants were recruited from 26-APRIL-2017 to 24-MAY-2017 at GI Labs (20 Victoria St., Toronto ON, M5C 2N8).
A screening visit was conducted to ensure each participant met inclusion/exclusion criteria for the study. Participants that qualified for the study were separated into either the lean or the overweight group as per protocol (11 subjects/arm).Participants were assigned to a randomization schedule in order of enrollment within each group.
Participant milestones
| Measure |
Lean Participants
Participants with BMI \>18.5 and \<25.0kg/m². All participants received each of the 6 interventions in a randomized manner.
|
Overweight/Obese Participants
Participants with BMI ≥25.0 and \<35.0kg/m². All participants received each of the 6 interventions in a randomized manner.
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
11
|
|
Overall Study
Water Control
|
9
|
11
|
|
Overall Study
Placebo Capsules
|
9
|
11
|
|
Overall Study
2g Capsules
|
9
|
11
|
|
Overall Study
4g Capsules
|
9
|
11
|
|
Overall Study
2g Tablets
|
9
|
11
|
|
Overall Study
4g Tablets
|
9
|
11
|
|
Overall Study
COMPLETED
|
9
|
11
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Acute Effect of HP-211 (Axulin) on Blood Glucose and Serum Insulin Responses in Healthy Lean and Overweight Humans
Baseline characteristics by cohort
| Measure |
Lean Participants
n=11 Participants
Participants with BMI \>18.5 and \<25.0kg/m². All participants received each of the 6 interventions in a randomized manner.
|
Overweight/Obese Participants
n=11 Participants
Participants with BMI ≥25.0 and \<35.0kg/m². All participants received each of the 6 interventions in a randomized manner.
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
34.1 years
STANDARD_DEVIATION 9.1 • n=99 Participants
|
45 years
STANDARD_DEVIATION 13 • n=107 Participants
|
39.5 years
STANDARD_DEVIATION 12.3 • n=206 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
4 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Korean
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Latin American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Chinese
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
South Asian
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
South East Asian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Region of Enrollment
Canada
|
11 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Body Mass Index (BMI)
|
22.2 kg/m2
STANDARD_DEVIATION 1.7 • n=99 Participants
|
28.5 kg/m2
STANDARD_DEVIATION 2.7 • n=107 Participants
|
25.4 kg/m2
STANDARD_DEVIATION 3.9 • n=206 Participants
|
PRIMARY outcome
Timeframe: 0, 15, 30, 45, 60, 90, and 120 minutes post-dosePopulation: The analysis of primary outcome data is based on all randomized subjects who received this intervention and for whom primary outcome data is known. There is no missing value imputation.
Percentage change in the incremental area under the glucose response curve (AUC) after 75g glucose for capsules and tablets containing Axulin powder relative to the water control. Incremental AUC is the AUC below the curve above the fasting level; area below fasting is ignored. Percentage change will be calculated as 100 x (A-P)/P where A and P are the mean AUC's after Axulin and water control treatments, respectively. The blinded AUC results for the 6 treatments will be subjected to repeated measures analysis of variance (ANOVA) examining for the main effects of treatment and participant-group, and treatment\*group interaction. After demonstration of significant heterogeneity among the 6 coded treatments, differences between individual means will be assessed using Tukey's test to adjust for multiple comparisons. The code will be broken after this analysis has been done. The percentage changes will be considered to be significant if the difference in mean AUC is significant.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage Change in Area Under The Curve (AUC) for Blood Glucose 0-2 Hours
|
301.09 mmol x min/L
Standard Error 27.6405
|
258.66 mmol x min/L
Standard Error 27.6405
|
248.63 mmol x min/L
Standard Error 27.6405
|
274.13 mmol x min/L
Standard Error 27.1449
|
325.73 mmol x min/L
Standard Error 0.7879
|
306.19 mmol x min/L
Standard Error 52.3273
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 0, 15, 30, 45, 60, 90, and 120 minutes post-dosePopulation: The analysis of secondary outcome data is based on all randomized subjects who received this intervention and for whom secondary outcome data is known. There is no missing value imputation.
Incremental area under the blood glucose response curve (AUC) is the AUC below the glucose response curve above the fasting level; area below fasting is ignored. The blinded AUC results for the 6 treatments will be subjected to repeated measures analysis of variance (ANOVA) examining for the main effects of treatment and participant-group, and treatment\*group interaction. After demonstration of significant heterogeneity among the 6 coded treatments, differences between individual means will be assessed using Tukey's test to adjust for multiple comparisons. The code will be broken after this analysis has been done.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood Glucose Area Under The Curve (AUC) 0-2 Hours
|
301.09 mmol x min/L
Standard Error 27.6405
|
258.66 mmol x min/L
Standard Error 27.6405
|
248.63 mmol x min/L
Standard Error 27.6405
|
274.13 mmol x min/L
Standard Error 27.1449
|
325.73 mmol x min/L
Standard Error 0.7879
|
306.19 mmol x min/L
Standard Error 52.3273
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 0, 15, 30, 45, 60, 90, and 120 minutes post-dosePopulation: The analysis of secondary outcome data is based on all randomized subjects who received this intervention and for whom secondary outcome data is known. There is no missing value imputation.
Incremental area under the serum insulin response curve (AUC) is the AUC below the insulin response curve above the fasting level; area below fasting is ignored. The blinded AUC results for the 6 treatments will be subjected to repeated measures analysis of variance (ANOVA) examining for the main effects of treatment and participant-group, and treatment\*group interaction. After demonstration of significant heterogeneity among the 6 coded treatments, differences between individual means will be assessed using Tukey's test to adjust for multiple comparisons. The code will be broken after this analysis has been done.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Serum Insulin Area Under The Curve (AUC) 0-2 Hours
|
4379.31 uU x min/ml
Standard Error 625.35
|
4005.61 uU x min/ml
Standard Error 634.61
|
4787.44 uU x min/ml
Standard Error 634.61
|
4135.18 uU x min/ml
Standard Error 493.30
|
4452.09 uU x min/ml
Standard Error 461.79
|
4381.71 uU x min/ml
Standard Error 545.47
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 0, 15, 30, 45, 60, 90, and 120 minutes post-dosePopulation: The analysis of secondary outcome data is based on all randomized subjects who received this intervention and for whom secondary outcome data is known. There is no missing value imputation.
Percentage change in the incremental area under the insulin response curve (AUC) after 75g glucose for the capsules containing Axulin powder relative to the water control. Incremental AUC is the AUC below the curve above the fasting level; area below fasting is ignored. Percentage change will be calculated as 100 x (A-P)/P where A and P are the mean AUC's after Axulin and water control treatments, respectively. The blinded AUC results for the 6 treatments will be subjected to repeated measures analysis of variance (ANOVA) examining for the main effects of treatment and participant-group, and treatment\*group interaction. After demonstration of significant heterogeneity among the 6 coded treatments, differences between individual means will be assessed using Tukey's test to adjust for multiple comparisons. The code will be broken after this analysis has been done. The percentage changes will be considered to be significant if the difference in mean AUC is significant.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage Change in Area Under The Curve (AUC) for Serum Insulin 0-2 Hours
|
4379.31 uU x min/ml
Standard Error 625.35
|
4005.61 uU x min/ml
Standard Error 634.61
|
4787.44 uU x min/ml
Standard Error 634.61
|
4135.18 uU x min/ml
Standard Error 493.30
|
4452.09 uU x min/ml
Standard Error 461.79
|
4381.71 uU x min/ml
Standard Error 545.47
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and 30 minutesPopulation: The analysis of secondary outcome data is based on all randomized subjects who received this intervention and for whom secondary outcome data is known. There is no missing value imputation.
Insulinogenic Index is an index of the ability of a change in blood glucose to stimulate an increase in serum insulin. It is a unitless measure with higher numbers indicating improved beta cell function. It is calculated by dividing the change in serum insulin between 0 and 30 minutes by the change in blood glucose between 0 and 30 minutes.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Insulinogenic Index
|
11.462 Insulinogenic Index
Standard Error 2.276
|
15.540 Insulinogenic Index
Standard Error 2.769
|
17.436 Insulinogenic Index
Standard Error 2.879
|
15.059 Insulinogenic Index
Standard Error 3.401
|
13.785 Insulinogenic Index
Standard Error 2.772
|
13.580 Insulinogenic Index
Standard Error 2.586
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 0, 30, 60, 90, and 120 minutes post-dosePopulation: The analysis of secondary outcome data is based on all randomized subjects who received this intervention and for whom secondary outcome data is known. There is no missing value imputation.
Matsuda Insulin Sensitivity Index is an index of whole body insulin sensitivity derived from glucose and insulin responses after a 75g Oral Glucose Tolerance Test (OGTT). It is calculated by 10000 divided by the square root of (FG\*FI\*MG\*MI) where FG is fasting glucose, FI is fasting insulin, MG is the mean AUC for blood glucose at 0, 30, 60, 90 and 120 minutes and MI is the mean AUC for serum insulin at 0, 30, 60, 90 and 120 minutes.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Matsuda Insulin Sensitivity Index
|
206.116 Matsuda Insulin Sensitivity Index
Standard Error 25.116
|
165.289 Matsuda Insulin Sensitivity Index
Standard Error 20.926
|
155.64 Matsuda Insulin Sensitivity Index
Standard Error 15.775
|
186.468 Matsuda Insulin Sensitivity Index
Standard Error 23.788
|
167.004 Matsuda Insulin Sensitivity Index
Standard Error 15.441
|
189.457 Matsuda Insulin Sensitivity Index
Standard Error 17.999
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 0, 30, 60, 90, and 120 minutes post-dosePopulation: The analysis of secondary outcome data is based on all randomized subjects who received this intervention and for whom secondary outcome data is known. There is no missing value imputation.
Insulin Secretion-Sensitivity Index-2 (ISSI-2) is an index of β-cell function with insulin secretion adjusted for whole body insulin sensitivity. It is calculated by the total area under the curve for serum insulin divided by the area under the curve for blood glucose, and that result times the Matsuda insulin sensitivity index (defined above).
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
ISSI-2 Index of Beta-cell Function
|
816.475 Insulin Secretion-Sensitivity Index-2
Standard Error 50.412
|
705.232 Insulin Secretion-Sensitivity Index-2
Standard Error 49.158
|
773.354 Insulin Secretion-Sensitivity Index-2
Standard Error 60.735
|
727.130 Insulin Secretion-Sensitivity Index-2
Standard Error 43.000
|
783.328 Insulin Secretion-Sensitivity Index-2
Standard Error 46.155
|
880.822 Insulin Secretion-Sensitivity Index-2
Standard Error 60.298
|
—
|
—
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 0, 15, 30, 45, 60, 90, and 120 minutes post-dosePopulation: Arms/Groups are provided as appropriate. The analysis of other outcome measures is based on all randomized subjects who received this intervention and for whom the outcome data is known. There is no missing value imputation.
Percentage change in blood glucose area under the curve (AUC) in lean participants compared to overweight participants.
Outcome measures
| Measure |
Water Control
n=9 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=11 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=9 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=11 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=9 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=11 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
n=9 Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
n=11 Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
n=9 Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
n=11 Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
n=9 Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
n=11 Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Effect of Axulin in Lean vs. Overweight Participants
|
337.704 mmol x min/L
Standard Error 26.343
|
264.474 mmol x min/L
Standard Error 31.965
|
286.425 mmol x min/L
Standard Error 30.944
|
230.891 mmol x min/L
Standard Error 35.892
|
291.083 mmol x min/L
Standard Error 50.563
|
206.168 mmol x min/L
Standard Error 32.895
|
326.517 mmol x min/L
Standard Error 34.054
|
324.941 mmol x min/L
Standard Error 48.047
|
358.513 mmol x min/L
Standard Error 38.841
|
253.858 mmol x min/L
Standard Error 33.223
|
290.325 mmol x min/L
Standard Error 54.912
|
243.699 mmol x min/L
Standard Error 39.663
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 0, 15, 30, 45, 60, 90, and 120 minutes post-dosePopulation: The analysis of the outcome measure is based on all randomized participants who received this intervention and for whom the outcome data is known. There is no missing value imputation.
Percentage change in blood glucose area under the curve (AUC) elicited by capsules compared to the same dose of tablets.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Effect of Capsules vs. Tablets
|
297.428 mmol x min/L
Standard Error 22.296
|
255.881 mmol x min/L
Standard Error 24.383
|
325.650 mmol x min/L
Standard Error 29.800
|
244.380 mmol x min/L
Standard Error 29.859
|
300.953 mmol x min/L
Standard Error 27.350
|
264.681 mmol x min/L
Standard Error 32.481
|
—
|
—
|
—
|
—
|
—
|
—
|
POST_HOC outcome
Timeframe: From Baseline at 90 minutesPopulation: The analysis of the outcome measure is based on all randomized participants who received this intervention and for whom the outcome data is known. The comparison is between the water control and the placebo capsules only. There is no missing value imputation.
Change from baseline (CFB) in blood glucose will be computed at 90 minutes. The CFB results for the water control and the placebo capsule treatments will be subjected to a paired t-test examining whether the mean difference between the two sets of observations is equal to zero.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood Glucose Change From Baseline in the Water Control Compared to the Placebo Capsules at 90 Minutes for All Participants
|
2.475 mmol/L
Standard Error 0.2736
|
1.953 mmol/L
Standard Error 0.2969
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
POST_HOC outcome
Timeframe: 1-2 hours post-dosePopulation: The analysis of other outcome measures is based on all randomized subjects who received this intervention and for whom the outcome data is known. There is no missing value imputation.
Incremental area under the blood glucose response curve (AUC) will be computed using the values recorded at 60 minutes and beyond. The blinded AUC results for the Axulin capsule treatments and the water control will be subjected to repeated measures analysis of variance (ANOVA) examining for the main effects of treatment and participant-group, and treatment\*group interaction. After demonstration of significant heterogeneity among the 3 coded treatments, differences between individual means will be assessed using Tukey's test to adjust for multiple comparisons.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
60-Minute Blood Glucose Area Under the Curve (AUC)
|
139.300 mmol x min/L
Standard Error 13.533
|
105.566 mmol x min/L
Standard Error 11.417
|
104.450 mmol x min/L
Standard Error 15.392
|
118.316 mmol x min/L
Standard Error 15.907
|
153.618 mmol x min/L
Standard Error 18.640
|
135.475 mmol x min/L
Standard Error 16.844
|
—
|
—
|
—
|
—
|
—
|
—
|
POST_HOC outcome
Timeframe: From Baseline at 90 and 120 minutesPopulation: The analysis of other outcome measures is based on all randomized subjects who received this intervention and for whom the outcome data is known. There is no missing value imputation.
Change from baseline (CFB) in blood glucose will be computed at 90 and 120 minutes. The CFB results for the capsule treatments and the water control will be subjected to a paired t-test examining whether the mean difference between the two sets of observations is equal to zero.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants
90-Minute Blood Glucose CFB
|
2.475 mmol/L
Standard Error 0.274
|
1.577 mmol/L
Standard Error 0.252
|
1.653 mmol/L
Standard Error 0.291
|
1.953 mmol/L
Standard Error .297
|
2.338 mmol/L
Standard Error .378
|
2.089 mmol/L
Standard Error .289
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants
120-Minute Blood Glucose CFB
|
1.469 mmol/L
Standard Error 0.245
|
0.686 mmol/L
Standard Error 0.249
|
0.790 mmol/L
Standard Error 0.228
|
1.032 mmol/L
Standard Error .258
|
1.453 mmol/L
Standard Error .256
|
1.507 mmol/L
Standard Error .313
|
—
|
—
|
—
|
—
|
—
|
—
|
POST_HOC outcome
Timeframe: From Baseline at 90 and 120 minutesPopulation: Arms/Groups are provided as appropriate. The analysis of other outcome measures is based on all randomized subjects who received this intervention and for whom the outcome data is known. There is no missing value imputation.
Change from baseline (CFB) in blood glucose will be computed at 90 and 120 minutes for the Lean Participants. The CFB results for the capsule treatments and the water control will be subjected to a paired t-test examining whether the mean difference between the two sets of observations is equal to zero.
Outcome measures
| Measure |
Water Control
n=9 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=9 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=9 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=9 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=9 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=9 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants
90-Minute Blood Glucose CFB in Lean Participants
|
2.902 mmol/L
Standard Error 0.238
|
1.992 mmol/L
Standard Error 0.379
|
2.022 mmol/L
Standard Error 0.505
|
2.546 mmol/L
Standard Error .457
|
2.542 mmol/L
Standard Error .366
|
2.818 mmol/L
Standard Error .426
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants
120-Minute Blood Glucose CFB in Lean Participants
|
2.232 mmol/L
Standard Error 0.206
|
1.340 mmol/L
Standard Error 0.361
|
1.299 mmol/L
Standard Error 0.366
|
1.710 mmol/L
Standard Error .438
|
1.857 mmol/L
Standard Error .359
|
2.479 mmol/L
Standard Error .354
|
—
|
—
|
—
|
—
|
—
|
—
|
POST_HOC outcome
Timeframe: From Baseline at 90 and 120 minutesPopulation: Arms/Groups are provided as appropriate. The analysis of other outcome measures is based on all randomized subjects who received this intervention and for whom the outcome data is known. There is no missing value imputation.
Change from baseline (CFB) in blood glucose will be computed at 90 and 120 minutes for the Obese/Overweight Participants. The CFB results for the capsule treatments and the water control will be subjected to a paired t-test examining whether the mean difference between the two sets of observations is equal to zero.
Outcome measures
| Measure |
Water Control
n=11 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=11 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=11 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=11 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=11 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=11 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants
90-Min Blood Glucose CFB, Overweight Participants
|
2.126 mmol/L
Standard Error 0.441
|
1.237 mmol/L
Standard Error 0.316
|
1.351 mmol/L
Standard Error 0.326
|
1.469 mmol/L
Standard Error .340
|
2.171 mmol/L
Standard Error .632
|
1.491 mmol/L
Standard Error .301
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants
120-Min Blood Glucose CFB, Overweight Participants
|
0.844 mmol/L
Standard Error 0.305
|
0.151 mmol/L
Standard Error 0.257
|
0.373 mmol/L
Standard Error 0.230
|
.477 mmol/L
Standard Error .190
|
1.122 mmol/L
Standard Error .342
|
.711 mmol/L
Standard Error .338
|
—
|
—
|
—
|
—
|
—
|
—
|
POST_HOC outcome
Timeframe: From Baseline at 90 minutesPopulation: The analysis of other outcome measures is based on all randomized subjects who received this intervention and for whom the outcome data is known. There is no missing value imputation.
Change from baseline (CFB) in insulin will be computed at 90 minutes. The CFB results for the capsule treatments and the water control will be subjected to a paired t-test examining whether the mean difference between the two sets of observations is equal to zero.
Outcome measures
| Measure |
Water Control
n=20 Participants
All Participants randomized to receive 250ml water.
|
2g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
|
4g Capsules
n=20 Participants
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
|
Placebo Capsules
n=20 Participants
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
2g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets
n=20 Participants
All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
2g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
2g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder.
|
4g Tablets, Lean Participants
Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
4g Tablets, Overweight Participants
Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder.
|
Placebo Capsules, Lean Participants
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
Placebo Capsules, Overweight Participants
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Insulin Change From Baseline at 90 Minutes in All Participants
|
48.345 uU/mL
Standard Error 10.046
|
25.896 uU/mL
Standard Error 4.174
|
38.851 uU/mL
Standard Error 12.260
|
38.179 uU/mL
Standard Error 6.175
|
37.152 uU/mL
Standard Error 5.383
|
38.388 uU/mL
Standard Error 7.536
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Water Control, Lean Participants
Water Control, Overweight/Obese Participants
Placebo Capsules, Lean Participants
Placebo Capsules, Overweight/Obese Participants
2g Capsules, Lean Participants
2g Capsules, Overweight/Obese Participants
4g Capsules, Lean Participants
4g Capsules, Overweight/Obese Participants
2g Tablets, Lean Participants
2g Tablets, Overweight/Obese Participants
4g Tablets, Lean Participants
4g Tablets, Overweight/Obese Participants
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place