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| Name | Class |
|---|---|
| Glycemic Index Laboratories, Inc | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lean Participants | Other | Participants with BMI >18.5 and <25.0kg/m² |
|
| Overweight/Obese Participants | Other | Participants with BMI ≥25.0 and <35.0kg/m² |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo capsules | Other | 250ml water with 16 x 250mg placebo capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
| Effect of Capsules vs. Tablets |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas MS Wolever, MD, PhD | Glycemic Index Laboratories, Inc | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Glycemic Index Laboratories, Inc. | Toronto | Ontario | M5C 2N8 | Canada |
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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 were recruited from 26-APRIL-2017 to 24-MAY-2017 at GI Labs (20 Victoria St., Toronto ON, M5C 2N8).
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| ID | Title | Description |
|---|---|---|
| FG000 | Lean Participants | Participants with BMI >18.5 and <25.0kg/m². All participants received each of the 6 interventions in a randomized manner. |
| FG001 | Overweight/Obese Participants |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 22, 2016 |
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Each participant in 2 participant groups will undergo each of 6 treatments
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Capsule treatments will be fully blinded. Tablet treatments will be open label.
| 2g capsules | Other | 250ml water with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules |
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| 4g capsules | Other | 250ml water with 16 x 250mg capsules containing Axulin powder |
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| Water Control | Other | 250ml water |
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| 2g tablets | Other | 250ml water with 2 x 1g tablets containing Axulin powder |
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| 4g tablets | Other | 250ml water with 4 x 1g tablets containing Axulin powder |
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| 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
| 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. | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
| 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. | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
| 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. | Baseline and 30 minutes |
| 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. | 0, 30, 60, 90, and 120 minutes post-dose |
| 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). | 0, 30, 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.
| 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
Participants with BMI ≥25.0 and <35.0kg/m². All participants received each of the 6 interventions in a randomized manner.
| Water Control |
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| Placebo Capsules |
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| 2g Capsules |
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| 4g Capsules |
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| 2g Tablets |
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| 4g Tablets |
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| COMPLETED |
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| NOT COMPLETED |
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The analysis of baseline characteristics includes all enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Lean Participants | Participants with BMI >18.5 and <25.0kg/m². All participants received each of the 6 interventions in a randomized manner. |
| BG001 | Overweight/Obese Participants | Participants with BMI ≥25.0 and <35.0kg/m². All participants received each of the 6 interventions in a randomized manner. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Least Squares Mean | Standard Error | mmol x min/L | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | mmol x min/L | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | uU x min/ml | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | uU x min/ml | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
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| 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. | 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. | Posted | Mean | Standard Error | Insulinogenic Index | Baseline and 30 minutes |
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| 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. | 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. | Posted | Mean | Standard Error | Matsuda Insulin Sensitivity Index | 0, 30, 60, 90, and 120 minutes post-dose |
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| 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). | 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. | Posted | Mean | Standard Error | Insulin Secretion-Sensitivity Index-2 | 0, 30, 60, 90, and 120 minutes post-dose |
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| 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. | 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. | Posted | Mean | Standard Error | mmol x min/L | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
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| 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. | 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. | Posted | Mean | Standard Error | mmol x min/L | 0, 15, 30, 45, 60, 90, and 120 minutes post-dose |
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| 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. | 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. | Posted | Mean | Standard Error | mmol/L | From Baseline at 90 minutes |
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| 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. | 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. | Posted | Mean | Standard Error | mmol x min/L | 1-2 hours post-dose |
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| 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. | 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. | Posted | Mean | Standard Error | mmol/L | From Baseline at 90 and 120 minutes |
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| 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. | 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. | Posted | Mean | Standard Error | mmol/L | From Baseline at 90 and 120 minutes |
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| 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. | 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. | Posted | Mean | Standard Error | mmol/L | From Baseline at 90 and 120 minutes |
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| 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. | 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. | Posted | Mean | Standard Error | uU/mL | From Baseline at 90 minutes |
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Adverse events were monitored for each participant from the time informed consent was signed through study completion; April 26, 2017 - June 21, 2017, an average of 2 months.
Serious classification based on the FDA regulatory definition of a serious Adverse Event.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Water Control, Lean Participants | Participants randomized to receive 250ml water. | 0 | 9 | 0 | 9 | 0 | 9 |
| EG001 | Water Control, Overweight/Obese Participants | Participants randomized to receive 250ml water. | 0 | 11 | 0 | 11 | 0 | 11 |
| EG002 | Placebo Capsules, Lean Participants | Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. | 0 | 9 | 0 | 9 | 0 | 9 |
| EG003 | Placebo Capsules, Overweight/Obese Participants | Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. | 0 | 11 | 0 | 11 | 0 | 11 |
| EG004 | 2g Capsules, Lean Participants | Participants randomized to receive 250ml water.with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules. | 0 | 9 | 0 | 9 | 0 | 9 |
| EG005 | 2g Capsules, Overweight/Obese Participants | Participants randomized to receive 250ml water.with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules. | 0 | 11 | 0 | 11 | 0 | 11 |
| EG006 | 4g Capsules, Lean Participants | Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder. | 0 | 9 | 0 | 9 | 0 | 9 |
| EG007 | 4g Capsules, Overweight/Obese Participants | Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder. | 0 | 11 | 0 | 11 | 0 | 11 |
| EG008 | 2g Tablets, Lean Participants | Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. | 0 | 9 | 0 | 9 | 0 | 9 |
| EG009 | 2g Tablets, Overweight/Obese Participants | Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. | 0 | 11 | 0 | 11 | 0 | 11 |
| EG010 | 4g Tablets, Lean Participants | Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. | 0 | 9 | 0 | 9 | 0 | 9 |
| EG011 | 4g Tablets, Overweight/Obese Participants | Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. | 0 | 11 | 0 | 11 | 0 | 11 |
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Note: The dissolution time for the tablets is substantially longer (>60 min) than it is for the capsules, so it would not be expected that the tablet formulation would exhibit a pharmacologic response if administered only 40 minutes before the GTT.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Project Manager | Housey Healthcare ULC | 2486637000 | info@housey.com |
| Oct 11, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| Male |
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| Caucasian |
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| Korean |
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| Latin American |
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| Chinese |
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| South Asian |
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| South East Asian |
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| 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. | t-test, 2 sided | 0.0519 | Percentage Change from Control | -17.42 | 2-Sided | Other |
| 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. | Percentage Change from Control | -8.95 | 2-Sided | Other |
All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
| OG003 | Placebo Capsules | All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG004 | 2g Tablets | All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder.
| OG003 | Placebo Capsules | All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG004 | 2g Tablets | All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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All Participants randomized to receive 250ml water.with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
| OG002 | 4g Capsules | All Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder. |
| OG003 | Placebo Capsules | All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG004 | 2g Tablets | All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG004 | 2g Tablets | All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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| OG003 | Placebo Capsules | All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG004 | 2g Tablets | All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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| Placebo Capsules |
All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG004 | 2g Tablets | All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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Overweight Participants randomized to receive 250ml water.with 8 x 250mg capsules containing Axulin powder plus 8 x 250mg placebo capsules.
| OG004 | 4g Capsules, Lean Participants | Lean Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder. |
| OG005 | 4g Capsules, Overweight Participants | Overweight Participants randomized to receive 250ml water with 16 x 250mg capsules containing Axulin powder. |
| OG006 | 2g Tablets, Lean Participants | Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG007 | 2g Tablets, Overweight Participants | Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG008 | 4g Tablets, Lean Participants | Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
| OG009 | 4g Tablets, Overweight Participants | Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
| OG010 | Placebo Capsules, Lean Participants | Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG011 | Placebo Capsules, Overweight Participants | Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
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| OG004 | 4g Tablets | All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
| OG005 | Placebo Capsules | All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
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| OG003 | Placebo Capsules | All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG004 | 2g Tablets | All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG004 | 2g Tablets | All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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| Placebo Capsules |
Lean Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG004 | 2g Tablets | Lean Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | Lean Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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| Placebo Capsules |
Overweight Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules. |
| OG004 | 2g Tablets | Overweight Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | Overweight Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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All Participants randomized to receive 250ml water.with 16 x 250mg placebo capsules.
| OG004 | 2g Tablets | All Participants randomized to receive 250ml water with 2 x 1g tablets containing Axulin powder. |
| OG005 | 4g Tablets | All Participants randomized to receive 250ml water with 4 x 1g tablets containing Axulin powder. |
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