Insulin Resistance, Diabetes
Conditions
Brief summary
Blood sugar levels are controlled by insulin, a hormone made by cells in the pancreas. After a meal, carbohydrates are broken down into glucose (blood sugar) which is absorbed from the intestine into the blood leading to a rise in glucose which triggers the secretion of insulin. Insulin binds to cells in the liver, muscle and fat, triggering them to take up glucose and bring the blood glucose level back to normal. A high blood sugar level is known as diabetes. The most common form of diabetes, type 2 diabetes, is caused by insulin resistance; that is, a reduced ability of insulin to stimulate glucose uptake into cells. The body compensates for insulin resistance by making more insulin; type 2 diabetes occurs when the pancreas can no longer make enough insulin to control blood glucose. The high blood glucose and insulin levels lead to long-term complications such as heart attacks, kidney failure, reduced sensation and poor circulation in the feet and legs. Reducing blood glucose levels with oral medications and insulin reduces risk of diabetic complications. There are several types of oral medications available for treating diabetes; however, they do not always control blood glucose adequately. In addition, these drugs have complications and are not used to treat insulin resistance and prediabetes - a condition when blood glucose is higher than normal but not high enough to be classified as diabetes. Prediabetes often progresses to diabetes over a period of months or years. Effective and safe treatments for prediabetes could prevent or delay the onset of diabetes. Axulin is a natural health product consisting of a mixture of extracts - derived from herbs and vegetables present in normal diets - which has been shown in cell culture and in animal studies to increase the ability of insulin to stimulate glucose uptake into cells. The active ingredient in Axulin is a botanical extract designated HP-211. Thus, HP-211 may reduce the blood glucose and insulin levels of subjects without diabetes after eating. HP-211 may also reduce glucose and insulin responses to a larger extent in insulin-resistant as compared to insulin-sensitive subjects. Subjects will take 0g, 2g, or 4g of capsules or tablets in the morning after an overnight fast; 40 minutes later they will consume 75g glucose dissolved in 300ml water. Blood glucose, insulin and fats will be measured before and for 2 hours after the glucose drink.
Detailed description
After consumption of a meal, pancreatic secretions of various digestive enzymes results in the breakdown of carbohydrates into monosaccharides including glucose. These sugars are subsequently absorbed through the intestinal lumen, resulting in an increased plasma glucose concentration. In response to high glucose levels, pancreatic beta-cells are stimulated to release the hormone insulin which circulates through the bloodstream and binds to insulin-responsive cells including adipocytes (fat tissue), myocytes (muscle tissue), and hepatocytes (liver). The resulting insulin-mediated signaling cascade initiates intracellular glucose uptake within peripheral tissues leading to a corresponding decrease in circulating plasma glucose. In insulin responsive cells glucose uptake stimulation begins after the binding of insulin to Insulin Receptors (IR), which are found on the membrane surface of cells in insulin responsive tissues such as fat, muscle and liver. The IR consists of an extracellular domain which binds to insulin, and an intracellular domain that has a protein tyrosine kinase activity. The binding of Insulin to the IR initiates a series of auto-phosphorylation events within the protein kinase domain that permit interaction and phosphorylation of downstream signaling proteins in the cell that mediate the cellular response to insulin. The resulting signaling complex includes proteins in the Insulin Receptor Substrate (IRS) family known as IRS-1 and IRS-2. These key targets of the insulin signaling pathway link IR activation to downstream signaling cascades that mediate intracellular processes including GLUT4-mediated glucose uptake. Prediabetes and Type II diabetes involve an impaired post-receptor response to insulin that hinders the glucose uptake response after meal consumption. Chronic hyperglycemia and the resulting compensatory hyperinsulinemia promote a cohort of acute and chronic sequelae including cardiovascular disease, liver complications, central nervous system degeneration and hyperglycemic osmotic stress. Axulin is a natural health product consisting of a mixture of extracts from herbs and vegetables present in normal diets which was identified by screening more than 100,000 compounds and extracts in a patented cell-culture based assay system targeting the IRS proteins. In vitro, Axulin's active ingredient, HP-211, has marked effects on the IRS-2 branch of the insulin signaling cascade to enhance downstream insulin signaling. HP-211 has been shown in animal models to increase glucose uptake in peripheral tissues and decrease circulating blood glucose and triglyceride concentrations. Regular supplementation of the diet with Axulin would be expected to reduce the incidence of associated prediabetic and diabetic complications, resulting in an increased quality of life for patients without resorting to current anti-diabetic prescription drugs such as metformin and others that may have substantial unwanted side effects in patients. HYPOTHESES Axulin will reduce postprandial glucose and insulin responses in a dose-dependent fashion in healthy subjects without diabetes. The reduction in glucose and insulin will be relatively greater in insulin-resistant than insulin-sensitive subjects. Subjects will take 0g, 2g, or 4g of capsules or tablets in the morning after an overnight fast; 40 minutes later they will consume 75g glucose dissolved in 300ml water. Blood glucose, insulin and triglycerides will be measured fasting and at intervals for 2 hours after the glucose drink.
Interventions
OTHERPlacebo capsules
250ml water with 16 x 250mg placebo capsules
OTHER2g capsules
250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules
OTHER4g capsules
250ml water with 16 x 250mg capsules containing Axulin powder
OTHERWater Control
250ml water
OTHER2g tablets
250ml water with 2 x 1g tablets containing Axulin powder
OTHER4g tablets
250ml water with 4 x 1g tablets containing Axulin powder
Sponsors
Glycemic Index Laboratories, Inc
Housey Healthcare ULC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Capsule treatments will be fully blinded. Tablet treatments will be open label.
Intervention model description
Each participant in 2 participant groups will undergo each of 6 treatments
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants taking stable doses (for at least 4 weeks of signing the consent form) of the birth control pill, thyroxin replacement therapy, statins, fibrates, cholesterol absorption inhibitors, anti-hypertensive medications, asprin, non-steroidal anti-inflammatories and/or mild anxiolytics or sedatives can be included.
Exclusion criteria
* Fasting serum glucose \>6.9mmol/L (124mg/dL) * HbA1c \>6.4% * Fasting serum triglycerides \>4.5 mmol/L (399 mg/dL) * Fasting LDL cholesterol \>4.99 mmol/L (192 mg/dL) * Blood pressure \>149 systolic or \>89 diastolic * Serum creatinine, or aspartate- or alanine transaminases \>1.2 times upper limit of normal * White cell count, red blood cell count, hemoglobin or hematocrit outside normal range * Hospitalization for surgery or a medical condition within 3 months of signing the consent form * Use of any drug to treat diabetes * Use of medications other than those listed above or the presence of any condition which might, in the opinion of Dr. Wolever, either: 1) make participation dangerous to the subject or to others, or 2) affect the results * Allergy or sensitivity to tarragon, chromium, escarole, lettuce, microcrystalline cellulose, inulin, food colouring (FD&C Yellow#5 and Blue#1) or vegetable-based capsules (silicon dioxide, titanium dioxide, hydroxypropylmethylcellulose)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Area Under The Curve (AUC) for Blood Glucose 0-2 Hours | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Glucose Area Under The Curve (AUC) 0-2 Hours | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose | 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. |
| Serum Insulin Area Under The Curve (AUC) 0-2 Hours | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose | 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. |
| Percentage Change in Area Under The Curve (AUC) for Serum Insulin 0-2 Hours | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose | 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. |
| Matsuda Insulin Sensitivity Index | 0, 30, 60, 90, and 120 minutes post-dose | 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. |
| ISSI-2 Index of Beta-cell Function | 0, 30, 60, 90, and 120 minutes post-dose | 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). |
| Insulinogenic Index | Baseline and 30 minutes | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Effect of Axulin in Lean vs. Overweight Participants | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose | Percentage change in blood glucose area under the curve (AUC) in lean participants compared to overweight participants. |
| Effect of Capsules vs. Tablets | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose | Percentage change in blood glucose area under the curve (AUC) elicited by capsules compared to the same dose of tablets. |
Countries
Canada
Participant flow
Recruitment details
Participants were recruited from 26-APRIL-2017 to 24-MAY-2017 at GI Labs (20 Victoria St., Toronto ON, M5C 2N8).
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Lean Participants Participants with BMI \>18.5 and \<25.0kg/m². All participants received each of the 6 interventions in a randomized manner. | 11 |
| Overweight/Obese Participants Participants with BMI ≥25.0 and \<35.0kg/m². All participants received each of the 6 interventions in a randomized manner. | 11 |
| Total | 22 |
Baseline characteristics
| Characteristic | Lean Participants | Overweight/Obese Participants | Total |
|---|---|---|---|
| Age, Continuous | 34.1 years STANDARD_DEVIATION 9.1 | 45 years STANDARD_DEVIATION 13 | 39.5 years STANDARD_DEVIATION 12.3 |
| Body Mass Index (BMI) | 22.2 kg/m2 STANDARD_DEVIATION 1.7 | 28.5 kg/m2 STANDARD_DEVIATION 2.7 | 25.4 kg/m2 STANDARD_DEVIATION 3.9 |
| Race/Ethnicity, Customized Black | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 4 Participants | 7 Participants | 11 Participants |
| Race/Ethnicity, Customized Chinese | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Korean | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Latin American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized South Asian | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized South East Asian | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Canada | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 |
| other Total, other adverse events | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 |
| serious Total, serious adverse events | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 |
Outcome results
Primary
Percentage Change in Area Under The Curve (AUC) for Blood Glucose 0-2 Hours
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.
Time frame: 0, 15, 30, 45, 60, 90, and 120 minutes post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Water Control | Percentage Change in Area Under The Curve (AUC) for Blood Glucose 0-2 Hours | 301.09 mmol x min/L | Standard Error 27.6405 |
| 2g Capsules | Percentage Change in Area Under The Curve (AUC) for Blood Glucose 0-2 Hours | 258.66 mmol x min/L | Standard Error 27.6405 |
| 4g Capsules | Percentage Change in Area Under The Curve (AUC) for Blood Glucose 0-2 Hours | 248.63 mmol x min/L | Standard Error 27.6405 |
| Placebo Capsules | Percentage Change in Area Under The Curve (AUC) for Blood Glucose 0-2 Hours | 274.13 mmol x min/L | Standard Error 27.1449 |
| 2g Tablets | Percentage Change in Area Under The Curve (AUC) for Blood Glucose 0-2 Hours | 325.73 mmol x min/L | Standard Error 0.7879 |
| 4g Tablets | Percentage Change in Area Under The Curve (AUC) for Blood Glucose 0-2 Hours | 306.19 mmol x min/L | Standard Error 52.3273 |
Comparison: 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.p-value: 0.1146t-test, 2 sided
Comparison: 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.p-value: 0.0519t-test, 2 sided
Comparison: 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.
Secondary
Blood Glucose Area Under The Curve (AUC) 0-2 Hours
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.
Time frame: 0, 15, 30, 45, 60, 90, and 120 minutes post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Water Control | Blood Glucose Area Under The Curve (AUC) 0-2 Hours | 301.09 mmol x min/L | Standard Error 27.6405 |
| 2g Capsules | Blood Glucose Area Under The Curve (AUC) 0-2 Hours | 258.66 mmol x min/L | Standard Error 27.6405 |
| 4g Capsules | Blood Glucose Area Under The Curve (AUC) 0-2 Hours | 248.63 mmol x min/L | Standard Error 27.6405 |
| Placebo Capsules | Blood Glucose Area Under The Curve (AUC) 0-2 Hours | 274.13 mmol x min/L | Standard Error 27.1449 |
| 2g Tablets | Blood Glucose Area Under The Curve (AUC) 0-2 Hours | 325.73 mmol x min/L | Standard Error 0.7879 |
| 4g Tablets | Blood Glucose Area Under The Curve (AUC) 0-2 Hours | 306.19 mmol x min/L | Standard Error 52.3273 |
Comparison: 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 comparisonsp-value: 0.1146t-test, 2 sided
Comparison: 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 comparisonsp-value: 0.0519t-test, 2 sided
Secondary
Insulinogenic Index
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.
Time frame: Baseline and 30 minutes
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Water Control | Insulinogenic Index | 11.462 Insulinogenic Index | Standard Error 2.276 |
| 2g Capsules | Insulinogenic Index | 15.540 Insulinogenic Index | Standard Error 2.769 |
| 4g Capsules | Insulinogenic Index | 17.436 Insulinogenic Index | Standard Error 2.879 |
| Placebo Capsules | Insulinogenic Index | 15.059 Insulinogenic Index | Standard Error 3.401 |
| 2g Tablets | Insulinogenic Index | 13.785 Insulinogenic Index | Standard Error 2.772 |
| 4g Tablets | Insulinogenic Index | 13.580 Insulinogenic Index | Standard Error 2.586 |
p-value: 0.1234t-test, 2 sided
p-value: 0.0331t-test, 2 sided
Secondary
ISSI-2 Index of Beta-cell Function
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).
Time frame: 0, 30, 60, 90, and 120 minutes post-dose
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Water Control | ISSI-2 Index of Beta-cell Function | 816.475 Insulin Secretion-Sensitivity Index-2 | Standard Error 50.412 |
| 2g Capsules | ISSI-2 Index of Beta-cell Function | 705.232 Insulin Secretion-Sensitivity Index-2 | Standard Error 49.158 |
| 4g Capsules | ISSI-2 Index of Beta-cell Function | 773.354 Insulin Secretion-Sensitivity Index-2 | Standard Error 60.735 |
| Placebo Capsules | ISSI-2 Index of Beta-cell Function | 727.130 Insulin Secretion-Sensitivity Index-2 | Standard Error 43 |
| 2g Tablets | ISSI-2 Index of Beta-cell Function | 783.328 Insulin Secretion-Sensitivity Index-2 | Standard Error 46.155 |
| 4g Tablets | ISSI-2 Index of Beta-cell Function | 880.822 Insulin Secretion-Sensitivity Index-2 | Standard Error 60.298 |
p-value: 0.0509t-test, 2 sided
p-value: 0.5016t-test, 2 sided
Secondary
Matsuda Insulin Sensitivity Index
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.
Time frame: 0, 30, 60, 90, and 120 minutes post-dose
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Water Control | Matsuda Insulin Sensitivity Index | 206.116 Matsuda Insulin Sensitivity Index | Standard Error 25.116 |
| 2g Capsules | Matsuda Insulin Sensitivity Index | 165.289 Matsuda Insulin Sensitivity Index | Standard Error 20.926 |
| 4g Capsules | Matsuda Insulin Sensitivity Index | 155.64 Matsuda Insulin Sensitivity Index | Standard Error 15.775 |
| Placebo Capsules | Matsuda Insulin Sensitivity Index | 186.468 Matsuda Insulin Sensitivity Index | Standard Error 23.788 |
| 2g Tablets | Matsuda Insulin Sensitivity Index | 167.004 Matsuda Insulin Sensitivity Index | Standard Error 15.441 |
| 4g Tablets | Matsuda Insulin Sensitivity Index | 189.457 Matsuda Insulin Sensitivity Index | Standard Error 17.999 |
p-value: <0.05t-test, 2 sided
p-value: 0.0568t-test, 2 sided
Secondary
Percentage Change in Area Under The Curve (AUC) for Serum Insulin 0-2 Hours
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.
Time frame: 0, 15, 30, 45, 60, 90, and 120 minutes post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Water Control | Percentage Change in Area Under The Curve (AUC) for Serum Insulin 0-2 Hours | 4379.31 uU x min/ml | Standard Error 625.35 |
| 2g Capsules | Percentage Change in Area Under The Curve (AUC) for Serum Insulin 0-2 Hours | 4005.61 uU x min/ml | Standard Error 634.61 |
| 4g Capsules | Percentage Change in Area Under The Curve (AUC) for Serum Insulin 0-2 Hours | 4787.44 uU x min/ml | Standard Error 634.61 |
| Placebo Capsules | Percentage Change in Area Under The Curve (AUC) for Serum Insulin 0-2 Hours | 4135.18 uU x min/ml | Standard Error 493.3 |
| 2g Tablets | Percentage Change in Area Under The Curve (AUC) for Serum Insulin 0-2 Hours | 4452.09 uU x min/ml | Standard Error 461.79 |
| 4g Tablets | Percentage Change in Area Under The Curve (AUC) for Serum Insulin 0-2 Hours | 4381.71 uU x min/ml | Standard Error 545.47 |
Comparison: 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.p-value: 0.5827t-test, 2 sided
Comparison: 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.p-value: 0.5485t-test, 2 sided
Secondary
Serum Insulin Area Under The Curve (AUC) 0-2 Hours
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.
Time frame: 0, 15, 30, 45, 60, 90, and 120 minutes post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Water Control | Serum Insulin Area Under The Curve (AUC) 0-2 Hours | 4379.31 uU x min/ml | Standard Error 625.35 |
| 2g Capsules | Serum Insulin Area Under The Curve (AUC) 0-2 Hours | 4005.61 uU x min/ml | Standard Error 634.61 |
| 4g Capsules | Serum Insulin Area Under The Curve (AUC) 0-2 Hours | 4787.44 uU x min/ml | Standard Error 634.61 |
| Placebo Capsules | Serum Insulin Area Under The Curve (AUC) 0-2 Hours | 4135.18 uU x min/ml | Standard Error 493.3 |
| 2g Tablets | Serum Insulin Area Under The Curve (AUC) 0-2 Hours | 4452.09 uU x min/ml | Standard Error 461.79 |
| 4g Tablets | Serum Insulin Area Under The Curve (AUC) 0-2 Hours | 4381.71 uU x min/ml | Standard Error 545.47 |
Comparison: 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.p-value: 0.5827t-test, 2 sided
Comparison: 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.p-value: 0.5485t-test, 2 sided
Post Hoc
60-Minute Blood Glucose Area Under the Curve (AUC)
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.
Time frame: 1-2 hours post-dose
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Water Control | 60-Minute Blood Glucose Area Under the Curve (AUC) | 139.300 mmol x min/L | Standard Error 13.533 |
| 2g Capsules | 60-Minute Blood Glucose Area Under the Curve (AUC) | 105.566 mmol x min/L | Standard Error 11.417 |
| 4g Capsules | 60-Minute Blood Glucose Area Under the Curve (AUC) | 104.450 mmol x min/L | Standard Error 15.392 |
| Placebo Capsules | 60-Minute Blood Glucose Area Under the Curve (AUC) | 118.316 mmol x min/L | Standard Error 15.907 |
| 2g Tablets | 60-Minute Blood Glucose Area Under the Curve (AUC) | 153.618 mmol x min/L | Standard Error 18.64 |
| 4g Tablets | 60-Minute Blood Glucose Area Under the Curve (AUC) | 135.475 mmol x min/L | Standard Error 16.844 |
p-value: 0.0098t-test, 2 sided
p-value: 0.0391t-test, 2 sided
Post Hoc
Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants
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.
Time frame: From Baseline at 90 and 120 minutes
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Water Control | 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 |
| Water Control | 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 |
| 2g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants | 90-Minute Blood Glucose CFB | 1.577 mmol/L | Standard Error 0.252 |
| 2g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants | 120-Minute Blood Glucose CFB | 0.686 mmol/L | Standard Error 0.249 |
| 4g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants | 90-Minute Blood Glucose CFB | 1.653 mmol/L | Standard Error 0.291 |
| 4g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants | 120-Minute Blood Glucose CFB | 0.790 mmol/L | Standard Error 0.228 |
| Placebo Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants | 90-Minute Blood Glucose CFB | 1.953 mmol/L | Standard Error 0.297 |
| Placebo Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants | 120-Minute Blood Glucose CFB | 1.032 mmol/L | Standard Error 0.258 |
| 2g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants | 90-Minute Blood Glucose CFB | 2.338 mmol/L | Standard Error 0.378 |
| 2g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants | 120-Minute Blood Glucose CFB | 1.453 mmol/L | Standard Error 0.256 |
| 4g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants | 90-Minute Blood Glucose CFB | 2.089 mmol/L | Standard Error 0.289 |
| 4g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in All Participants | 120-Minute Blood Glucose CFB | 1.507 mmol/L | Standard Error 0.313 |
Comparison: Change from baseline (CFB) in blood glucose 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.p-value: 0.0034t-test, 2 sided
Comparison: Change from baseline (CFB) in blood glucose 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.p-value: 0.0058t-test, 2 sided
Comparison: Change from baseline (CFB) in blood glucose will be computed at 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.p-value: 0.0016t-test, 2 sided
Comparison: Change from baseline (CFB) in blood glucose will be computed at 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.p-value: 0.0125t-test, 2 sided
Post Hoc
Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants
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.
Time frame: From Baseline at 90 and 120 minutes
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Water Control | 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 |
| Water Control | 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 |
| 2g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants | 90-Minute Blood Glucose CFB in Lean Participants | 1.992 mmol/L | Standard Error 0.379 |
| 2g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants | 120-Minute Blood Glucose CFB in Lean Participants | 1.340 mmol/L | Standard Error 0.361 |
| 4g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants | 90-Minute Blood Glucose CFB in Lean Participants | 2.022 mmol/L | Standard Error 0.505 |
| 4g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants | 120-Minute Blood Glucose CFB in Lean Participants | 1.299 mmol/L | Standard Error 0.366 |
| Placebo Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants | 90-Minute Blood Glucose CFB in Lean Participants | 2.546 mmol/L | Standard Error 0.457 |
| Placebo Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants | 120-Minute Blood Glucose CFB in Lean Participants | 1.710 mmol/L | Standard Error 0.438 |
| 2g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants | 90-Minute Blood Glucose CFB in Lean Participants | 2.542 mmol/L | Standard Error 0.366 |
| 2g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants | 120-Minute Blood Glucose CFB in Lean Participants | 1.857 mmol/L | Standard Error 0.359 |
| 4g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants | 90-Minute Blood Glucose CFB in Lean Participants | 2.818 mmol/L | Standard Error 0.426 |
| 4g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in Lean Participants | 120-Minute Blood Glucose CFB in Lean Participants | 2.479 mmol/L | Standard Error 0.354 |
Comparison: Change from baseline (CFB) in blood glucose 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.p-value: 0.0788t-test, 2 sided
Comparison: Change from baseline (CFB) in blood glucose 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.p-value: 0.0887t-test, 2 sided
Comparison: Change from baseline (CFB) in blood glucose will be computed at 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.p-value: 0.0266t-test, 2 sided
Comparison: Change from baseline (CFB) in blood glucose will be computed at 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.p-value: 0.0455t-test, 2 sided
Post Hoc
Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants
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.
Time frame: From Baseline at 90 and 120 minutes
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Water Control | 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 |
| Water Control | 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 |
| 2g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants | 90-Min Blood Glucose CFB, Overweight Participants | 1.237 mmol/L | Standard Error 0.316 |
| 2g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants | 120-Min Blood Glucose CFB, Overweight Participants | 0.151 mmol/L | Standard Error 0.257 |
| 4g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants | 90-Min Blood Glucose CFB, Overweight Participants | 1.351 mmol/L | Standard Error 0.326 |
| 4g Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants | 120-Min Blood Glucose CFB, Overweight Participants | 0.373 mmol/L | Standard Error 0.23 |
| Placebo Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants | 90-Min Blood Glucose CFB, Overweight Participants | 1.469 mmol/L | Standard Error 0.34 |
| Placebo Capsules | Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants | 120-Min Blood Glucose CFB, Overweight Participants | .477 mmol/L | Standard Error 0.19 |
| 2g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants | 90-Min Blood Glucose CFB, Overweight Participants | 2.171 mmol/L | Standard Error 0.632 |
| 2g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants | 120-Min Blood Glucose CFB, Overweight Participants | 1.122 mmol/L | Standard Error 0.342 |
| 4g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants | 90-Min Blood Glucose CFB, Overweight Participants | 1.491 mmol/L | Standard Error 0.301 |
| 4g Tablets | Blood Glucose Change From Baseline at 90 and 120 Minutes in Overweight Participants | 120-Min Blood Glucose CFB, Overweight Participants | .711 mmol/L | Standard Error 0.338 |
Comparison: Change from baseline (CFB) in blood glucose 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.p-value: 0.0261t-test, 2 sided
Comparison: Change from baseline (CFB) in blood glucose 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.p-value: 0.0391t-test, 2 sided
Comparison: Change from baseline (CFB) in blood glucose will be computed at 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.p-value: 0.0372t-test, 2 sided
Comparison: Change from baseline (CFB) in blood glucose will be computed at 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.p-value: 0.1631t-test, 2 sided
Post Hoc
Blood Glucose Change From Baseline in the Water Control Compared to the Placebo Capsules at 90 Minutes for All Participants
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.
Time frame: From Baseline at 90 minutes
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Water Control | 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 |
| 2g Capsules | Blood Glucose Change From Baseline in the Water Control Compared to the Placebo Capsules at 90 Minutes for All Participants | 1.953 mmol/L | Standard Error 0.2969 |
p-value: 0.0374t-test, 2 sided
Other Pre-specified
Effect of Axulin in Lean vs. Overweight Participants
Percentage change in blood glucose area under the curve (AUC) in lean participants compared to overweight participants.
Time frame: 0, 15, 30, 45, 60, 90, and 120 minutes post-dose
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Water Control | Effect of Axulin in Lean vs. Overweight Participants | 337.704 mmol x min/L | Standard Error 26.343 |
| 2g Capsules | Effect of Axulin in Lean vs. Overweight Participants | 264.474 mmol x min/L | Standard Error 31.965 |
| 4g Capsules | Effect of Axulin in Lean vs. Overweight Participants | 286.425 mmol x min/L | Standard Error 30.944 |
| Placebo Capsules | Effect of Axulin in Lean vs. Overweight Participants | 230.891 mmol x min/L | Standard Error 35.892 |
| 2g Tablets | Effect of Axulin in Lean vs. Overweight Participants | 291.083 mmol x min/L | Standard Error 50.563 |
| 4g Tablets | Effect of Axulin in Lean vs. Overweight Participants | 206.168 mmol x min/L | Standard Error 32.895 |
| 2g Tablets, Lean Participants | Effect of Axulin in Lean vs. Overweight Participants | 326.517 mmol x min/L | Standard Error 34.054 |
| 2g Tablets, Overweight Participants | Effect of Axulin in Lean vs. Overweight Participants | 324.941 mmol x min/L | Standard Error 48.047 |
| 4g Tablets, Lean Participants | Effect of Axulin in Lean vs. Overweight Participants | 358.513 mmol x min/L | Standard Error 38.841 |
| 4g Tablets, Overweight Participants | Effect of Axulin in Lean vs. Overweight Participants | 253.858 mmol x min/L | Standard Error 33.223 |
| Placebo Capsules, Lean Participants | Effect of Axulin in Lean vs. Overweight Participants | 290.325 mmol x min/L | Standard Error 54.912 |
| Placebo Capsules, Overweight Participants | Effect of Axulin in Lean vs. Overweight Participants | 243.699 mmol x min/L | Standard Error 39.663 |
p-value: 0.8444t-test, 2 sided
p-value: 0.9681t-test, 2 sided
p-value: 0.1022t-test, 2 sided
p-value: 0.3738t-test, 2 sided
Other Pre-specified
Effect of Capsules vs. Tablets
Percentage change in blood glucose area under the curve (AUC) elicited by capsules compared to the same dose of tablets.
Time frame: 0, 15, 30, 45, 60, 90, and 120 minutes post-dose
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Water Control | Effect of Capsules vs. Tablets | 297.428 mmol x min/L | Standard Error 22.296 |
| 2g Capsules | Effect of Capsules vs. Tablets | 255.881 mmol x min/L | Standard Error 24.383 |
| 4g Capsules | Effect of Capsules vs. Tablets | 325.650 mmol x min/L | Standard Error 29.8 |
| Placebo Capsules | Effect of Capsules vs. Tablets | 244.380 mmol x min/L | Standard Error 29.859 |
| 2g Tablets | Effect of Capsules vs. Tablets | 300.953 mmol x min/L | Standard Error 27.35 |
| 4g Tablets | Effect of Capsules vs. Tablets | 264.681 mmol x min/L | Standard Error 32.481 |
p-value: 0.0111t-test, 2 sided
p-value: 0.1684t-test, 2 sided
Post Hoc
Insulin Change From Baseline at 90 Minutes in All Participants
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.
Time frame: From Baseline at 90 minutes
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Water Control | Insulin Change From Baseline at 90 Minutes in All Participants | 48.345 uU/mL | Standard Error 10.046 |
| 2g Capsules | Insulin Change From Baseline at 90 Minutes in All Participants | 25.896 uU/mL | Standard Error 4.174 |
| 4g Capsules | Insulin Change From Baseline at 90 Minutes in All Participants | 38.851 uU/mL | Standard Error 12.26 |
| Placebo Capsules | Insulin Change From Baseline at 90 Minutes in All Participants | 38.179 uU/mL | Standard Error 6.175 |
| 2g Tablets | Insulin Change From Baseline at 90 Minutes in All Participants | 37.152 uU/mL | Standard Error 5.383 |
| 4g Tablets | Insulin Change From Baseline at 90 Minutes in All Participants | 38.388 uU/mL | Standard Error 7.536 |
Comparison: 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.p-value: 0.0303t-test, 2 sided
Comparison: 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.p-value: 0.4283t-test, 2 sided