Diabetes Mellitus, Type 2
Conditions
Keywords
Diabetes Mellitus - Type 2, Diabetes Mellitus, Drug Therapy
Brief summary
The purpose of this study was to evaluate the dose-response relationships of alogliptin, once daily (QD) to an α-glucosidase inhibitor, three times daily (TID), to determine the optimal clinical dose for type 2 diabetic patients.
Detailed description
Both insulin hyposecretion and insulin-resistance are considered to be involved in the development of type 2 diabetes mellitus. Takeda is developing SYR-322 (alogliptin) for the improvement of glycemic control in patients with type 2 diabetes mellitus. Alogliptin is an inhibitor of the dipeptidyl peptidase IV (DPP-IV) enzyme. DPP-IV is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion. It is expected that inhibition of DPP-IV will improve glycemic control in patients with type 2 diabetes. To evaluate the long-term safety and efficacy of alogliptin, participants in the present study could enter a long-term extension study SYR-322/OCT-001 (NCT01263496) that was planned separately.
Interventions
DRUGAlogliptin
Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks
DRUGVoglibose
Voglibose 0.2 mg, tablets, orally, three times daily for up to 12 weeks.
DRUGPlacebo
Placebo-matching tablets, orally, once or three times daily for up to 12 weeks.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A glycosylated hemoglobin (HbA1c) value of 6.5% or more and below 10.0% 4 weeks after the start of screening(Week -4). * A HbA1c differences within 10.0%\* (\*rounded off to the first decimal point) at the start of screening (Week -8) and 4 weeks after the start of screening (Week -4) from the HbA1c value at the start of screening. * Was receiving a specific diet therapy and an exercise therapy (if any) for the last 4 weeks or longer before the start of screening (Week -8).
Exclusion criteria
* Received any antidiabetic drug within the last 4 weeks before the start of screening (Week -8) or during screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (Week 12). | Baseline and Week 12. | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 or final visit and glycosylated hemoglobin collected at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (Week 4). | Baseline and Week 4. | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 4 and glycosylated hemoglobin collected at baseline. |
| Change From Baseline in Glycosylated Hemoglobin (Week 8). | Baseline and Week 8. | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and glycosylated hemoglobin collected at baseline. |
| Change From Baseline in Fasting Plasma Glucose (Week 2). | Baseline and Week 2 | The change between the value of fasting plasma glucose collected at week 2 and fasting plasma glucose collected at baseline. |
| Change From Baseline in Fasting Plasma Glucose (Week 4). | Baseline and Week 4. | The change between the value of fasting plasma glucose collected at week 4 and fasting plasma glucose collected at baseline. |
| Change From Baseline in Fasting Plasma Glucose (Week 8). | Baseline and Week 8. | The change between the value of fasting plasma glucose collected at week 8 and fasting plasma glucose collected at baseline. |
| Change From Baseline in Fasting Plasma Glucose (Week 12). | Baseline and Week 12. | The change between the value of fasting plasma glucose collected at week 12 or final visit and fasting plasma glucose collected at baseline. |
| Change From Baseline in Fasting C-peptide (Week 2). | Baseline and Week 2. | The change between the value of fasting C-peptide collected at week 2 and fasting C-peptide collected at baseline. |
| Change From Baseline in Glycosylated Hemoglobin (Week 2). | Baseline and Week 2. | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 2 and glycosylated hemoglobin collected at baseline. |
| Change From Baseline in Fasting C-peptide (Week 8). | Baseline and Week 8. | The change between the value of fasting C-peptide collected at week 8 and fasting C-peptide collected at baseline. |
| Change From Baseline in Fasting C-peptide (Week 12). | Baseline and Week 12. | The change between the value of fasting C-peptide collected at week 12 or final visit and fasting C-peptide collected at baseline. |
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value). | Baseline and Week 12. | The change between the value of blood glucose collected at week 12 or final visit and blood glucose collected at baseline. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and at 2 hours after the start of the meal. |
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC (0-2)). | Baseline and Week 12. | The change between the value of blood glucose collected at week 12 or final visit and blood glucose collected at baseline. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and at 2 hours after the start of the meal. |
| Change From Baseline in Insulin Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC(0-2)). | Baseline and Week 12 | The change between the value of insulin collected at week 12 or final visit and insulin collected at baseline as measured by the meal tolerance test. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and 2 hours after the start of the meal. |
| Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2). | Baseline and Week 12. | The change between the value of C-peptide collected at week 12 or final visit and C-peptide collected at baseline as measured by the meal tolerance test. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and 2 hours after the start of the meal. |
| Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)). | Baseline and Week 12 | The change between the value of glucagons collected at week 12 or final visit and glucagons collected at baseline. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and 2 hours after the start of the meal. |
| Change From Baseline in Fasting C-peptide (Week 4). | Baseline and Week 4. | The change between the value of fasting C-peptide collected at week 4 and fasting C-peptide collected at baseline. |
Countries
Japan
Participant flow
Recruitment details
Participants enrolled at 54 investigative sites in Japan from 17 January 2007 to 22 December 2007.
Pre-assignment details
Participants with a historical diagnosis of type 2 diabetes mellitus with uncontrolled blood glucose despite diet and exercise therapies were enrolled in one of 6, once-daily (QD) or three-times daily (TID) treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo-matching tablets, orally, once or three times daily for up to 12 weeks. | 75 |
| Alogliptin 6.25 mg QD Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks. | 79 |
| Alogliptin 12.5 mg QD Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. | 84 |
| Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. | 80 |
| Alogliptin 50 mg QD Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. | 79 |
| Voglibose 0.2 mg TID Voglibose 0.2 mg, tablets, orally, three times daily for up to 12 weeks. | 83 |
| Total | 480 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 1 | 1 | 2 | 2 |
| Overall Study | Lack of Efficacy | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Participant Unavailability | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Study Drug Non-compliance | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Alogliptin 6.25 mg QD | Alogliptin 12.5 mg QD | Alogliptin 25 mg QD | Alogliptin 50 mg QD | Voglibose 0.2 mg TID | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized ≤ 64 years | 48 participants | 58 participants | 56 participants | 52 participants | 54 participants | 51 participants | 319 participants |
| Age, Customized ≥ 65 years | 27 participants | 21 participants | 28 participants | 28 participants | 25 participants | 32 participants | 161 participants |
| Sex: Female, Male Female | 19 Participants | 23 Participants | 25 Participants | 17 Participants | 24 Participants | 27 Participants | 135 Participants |
| Sex: Female, Male Male | 56 Participants | 56 Participants | 59 Participants | 63 Participants | 55 Participants | 56 Participants | 345 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 75 | 17 / 79 | 23 / 84 | 27 / 80 | 23 / 79 | 38 / 83 |
| serious Total, serious adverse events | 1 / 75 | 2 / 79 | 2 / 84 | 1 / 80 | 2 / 79 | 2 / 83 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (Week 12).
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 or final visit and glycosylated hemoglobin collected at baseline.
Time frame: Baseline and Week 12.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (Week 12). | 0.06 percentage of Glycosylated Hemoglobin | Standard Deviation 0.456 |
| Alogliptin 6.25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 12). | -0.51 percentage of Glycosylated Hemoglobin | Standard Deviation 0.677 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 12). | -0.70 percentage of Glycosylated Hemoglobin | Standard Deviation 0.572 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 12). | -0.76 percentage of Glycosylated Hemoglobin | Standard Deviation 0.547 |
| Alogliptin 50 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 12). | -0.82 percentage of Glycosylated Hemoglobin | Standard Deviation 0.474 |
| Voglibose 0.2 mg TID | Change From Baseline in Glycosylated Hemoglobin (Week 12). | -0.16 percentage of Glycosylated Hemoglobin | Standard Deviation 0.73 |
95% CI: [-0.755, -0.386]
95% CI: [-0.925, -0.598]
95% CI: [-0.987, -0.665]
95% CI: [-1.035, -0.739]
95% CI: [-0.57, -0.132]
95% CI: [-0.743, -0.342]
95% CI: [-0.808, -0.406]
95% CI: [-0.859, -0.475]
Secondary
Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value).
The change between the value of blood glucose collected at week 12 or final visit and blood glucose collected at baseline. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and at 2 hours after the start of the meal.
Time frame: Baseline and Week 12.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value). | -4.2 mg/dL | Standard Deviation 42.1 |
| Alogliptin 6.25 mg QD | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value). | -28.1 mg/dL | Standard Deviation 49.5 |
| Alogliptin 12.5 mg QD | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value). | -27.6 mg/dL | Standard Deviation 43.88 |
| Alogliptin 25 mg QD | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value). | -44.8 mg/dL | Standard Deviation 36.04 |
| Alogliptin 50 mg QD | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value). | -47.0 mg/dL | Standard Deviation 32.66 |
| Voglibose 0.2 mg TID | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value). | -22.7 mg/dL | Standard Deviation 40.58 |
95% CI: [-38.75, -8.94]
95% CI: [-37.14, -9.61]
95% CI: [-53.18, -28.02]
95% CI: [-54.93, -30.58]
95% CI: [-19.7, 8.98]
95% CI: [-18.13, 8.35]
95% CI: [-34.22, -10.01]
95% CI: [-35.98, -12.55]
Secondary
Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC (0-2)).
The change between the value of blood glucose collected at week 12 or final visit and blood glucose collected at baseline. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and at 2 hours after the start of the meal.
Time frame: Baseline and Week 12.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC (0-2)). | 5.6 mg·hr/dL | Standard Deviation 62.45 |
| Alogliptin 6.25 mg QD | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC (0-2)). | -52.7 mg·hr/dL | Standard Deviation 75.51 |
| Alogliptin 12.5 mg QD | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC (0-2)). | -55.0 mg·hr/dL | Standard Deviation 63.73 |
| Alogliptin 25 mg QD | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC (0-2)). | -73.1 mg·hr/dL | Standard Deviation 51.21 |
| Alogliptin 50 mg QD | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC (0-2)). | -81.8 mg·hr/dL | Standard Deviation 53.69 |
| Voglibose 0.2 mg TID | Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC (0-2)). | -50.0 mg·hr/dL | Standard Deviation 62.49 |
95% CI: [-80.79, -35.83]
95% CI: [-80.84, -40.47]
95% CI: [-97.03, -60.4]
95% CI: [-106.26, -68.6]
95% CI: [-24.69, 19.23]
95% CI: [-24.85, 14.7]
95% CI: [-41.16, -5.11]
95% CI: [-50.36, -13.33]
Secondary
Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2).
The change between the value of C-peptide collected at week 12 or final visit and C-peptide collected at baseline as measured by the meal tolerance test. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and 2 hours after the start of the meal.
Time frame: Baseline and Week 12.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2). | 0.01 ng·hr/mL | Standard Deviation 1.628 |
| Alogliptin 6.25 mg QD | Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2). | 0.54 ng·hr/mL | Standard Deviation 1.787 |
| Alogliptin 12.5 mg QD | Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2). | 0.77 ng·hr/mL | Standard Deviation 1.804 |
| Alogliptin 25 mg QD | Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2). | 1.01 ng·hr/mL | Standard Deviation 1.957 |
| Alogliptin 50 mg QD | Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2). | 0.97 ng·hr/mL | Standard Deviation 1.642 |
| Voglibose 0.2 mg TID | Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2). | -0.39 ng·hr/mL | Standard Deviation 2.091 |
95% CI: [-0.019, 1.089]
95% CI: [0.214, 1.315]
95% CI: [0.418, 1.58]
95% CI: [0.43, 1.489]
95% CI: [0.315, 1.552]
95% CI: [0.551, 1.774]
95% CI: [0.759, 2.036]
95% CI: [0.76, 1.956]
Secondary
Change From Baseline in Fasting C-peptide (Week 12).
The change between the value of fasting C-peptide collected at week 12 or final visit and fasting C-peptide collected at baseline.
Time frame: Baseline and Week 12.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting C-peptide (Week 12). | -0.00 ng/mL | Standard Deviation 0.692 |
| Alogliptin 6.25 mg QD | Change From Baseline in Fasting C-peptide (Week 12). | 0.04 ng/mL | Standard Deviation 0.967 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting C-peptide (Week 12). | 0.17 ng/mL | Standard Deviation 0.609 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting C-peptide (Week 12). | 0.25 ng/mL | Standard Deviation 0.591 |
| Alogliptin 50 mg QD | Change From Baseline in Fasting C-peptide (Week 12). | 0.18 ng/mL | Standard Deviation 0.696 |
| Voglibose 0.2 mg TID | Change From Baseline in Fasting C-peptide (Week 12). | -0.02 ng/mL | Standard Deviation 0.888 |
95% CI: [-0.23, 0.308]
95% CI: [-0.029, 0.379]
95% CI: [0.044, 0.453]
95% CI: [-0.035, 0.407]
95% CI: [-0.236, 0.34]
95% CI: [-0.044, 0.421]
95% CI: [0.026, 0.496]
95% CI: [-0.049, 0.448]
Secondary
Change From Baseline in Fasting C-peptide (Week 2).
The change between the value of fasting C-peptide collected at week 2 and fasting C-peptide collected at baseline.
Time frame: Baseline and Week 2.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting C-peptide (Week 2). | 0.04 ng/mL | Standard Deviation 0.772 |
| Alogliptin 6.25 mg QD | Change From Baseline in Fasting C-peptide (Week 2). | -0.11 ng/mL | Standard Deviation 0.731 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting C-peptide (Week 2). | 0.17 ng/mL | Standard Deviation 0.756 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting C-peptide (Week 2). | 0.18 ng/mL | Standard Deviation 0.776 |
| Alogliptin 50 mg QD | Change From Baseline in Fasting C-peptide (Week 2). | 0.04 ng/mL | Standard Deviation 0.619 |
| Voglibose 0.2 mg TID | Change From Baseline in Fasting C-peptide (Week 2). | -0.11 ng/mL | Standard Deviation 0.83 |
95% CI: [-0.384, 0.094]
95% CI: [-0.106, 0.374]
95% CI: [-0.103, 0.39]
95% CI: [-0.218, 0.227]
95% CI: [-0.241, 0.245]
95% CI: [0.038, 0.524]
95% CI: [0.041, 0.54]
95% CI: [-0.077, 0.38]
Secondary
Change From Baseline in Fasting C-peptide (Week 4).
The change between the value of fasting C-peptide collected at week 4 and fasting C-peptide collected at baseline.
Time frame: Baseline and Week 4.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting C-peptide (Week 4). | 0.01 ng/mL | Standard Deviation 0.624 |
| Alogliptin 6.25 mg QD | Change From Baseline in Fasting C-peptide (Week 4). | -0.04 ng/mL | Standard Deviation 0.634 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting C-peptide (Week 4). | 0.02 ng/mL | Standard Deviation 0.636 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting C-peptide (Week 4). | 0.16 ng/mL | Standard Deviation 0.697 |
| Alogliptin 50 mg QD | Change From Baseline in Fasting C-peptide (Week 4). | 0.05 ng/mL | Standard Deviation 0.554 |
| Voglibose 0.2 mg TID | Change From Baseline in Fasting C-peptide (Week 4). | -0.16 ng/mL | Standard Deviation 0.767 |
95% CI: [-0.245, 0.156]
95% CI: [-0.185, 0.21]
95% CI: [-0.053, 0.369]
95% CI: [-0.14, 0.235]
95% CI: [-0.097, 0.341]
95% CI: [-0.036, 0.395]
95% CI: [0.097, 0.553]
95% CI: [0.006, 0.423]
Secondary
Change From Baseline in Fasting C-peptide (Week 8).
The change between the value of fasting C-peptide collected at week 8 and fasting C-peptide collected at baseline.
Time frame: Baseline and Week 8.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting C-peptide (Week 8). | 0.17 ng/mL | Standard Deviation 0.882 |
| Alogliptin 6.25 mg QD | Change From Baseline in Fasting C-peptide (Week 8). | 0.05 ng/mL | Standard Deviation 1.144 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting C-peptide (Week 8). | 0.07 ng/mL | Standard Deviation 0.792 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting C-peptide (Week 8). | 0.24 ng/mL | Standard Deviation 0.646 |
| Alogliptin 50 mg QD | Change From Baseline in Fasting C-peptide (Week 8). | 0.05 ng/mL | Standard Deviation 0.592 |
| Voglibose 0.2 mg TID | Change From Baseline in Fasting C-peptide (Week 8). | -0.05 ng/mL | Standard Deviation 0.804 |
95% CI: [-0.444, 0.209]
95% CI: [-0.362, 0.162]
95% CI: [-0.166, 0.324]
95% CI: [-0.355, 0.121]
95% CI: [-0.203, 0.408]
95% CI: [-0.124, 0.364]
95% CI: [0.071, 0.526]
95% CI: [-0.118, 0.322]
Secondary
Change From Baseline in Fasting Plasma Glucose (Week 12).
The change between the value of fasting plasma glucose collected at week 12 or final visit and fasting plasma glucose collected at baseline.
Time frame: Baseline and Week 12.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 12). | 5.6 mg/dL | Standard Deviation 25.26 |
| Alogliptin 6.25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 12). | -9.3 mg/dL | Standard Deviation 32.36 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 12). | -14.6 mg/dL | Standard Deviation 23.8 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 12). | -17.5 mg/dL | Standard Deviation 20.71 |
| Alogliptin 50 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 12). | -22.6 mg/dL | Standard Deviation 24.24 |
| Voglibose 0.2 mg TID | Change From Baseline in Fasting Plasma Glucose (Week 12). | -3.0 mg/dL | Standard Deviation 27.69 |
95% CI: [-24.19, -5.64]
95% CI: [-27.86, -12.48]
95% CI: [-30.41, -15.73]
95% CI: [-36.05, -20.29]
95% CI: [-15.6, 3.06]
95% CI: [-19.41, -3.64]
95% CI: [-22.04, -6.8]
95% CI: [-27.61, -11.43]
Secondary
Change From Baseline in Fasting Plasma Glucose (Week 2).
The change between the value of fasting plasma glucose collected at week 2 and fasting plasma glucose collected at baseline.
Time frame: Baseline and Week 2
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 2). | 1.8 mg/dL | Standard Deviation 28.26 |
| Alogliptin 6.25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 2). | -13.8 mg/dL | Standard Deviation 19.31 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 2). | -15.9 mg/dL | Standard Deviation 20.26 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 2). | -14.3 mg/dL | Standard Deviation 22.13 |
| Alogliptin 50 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 2). | -21.7 mg/dL | Standard Deviation 25.65 |
| Voglibose 0.2 mg TID | Change From Baseline in Fasting Plasma Glucose (Week 2). | -8.0 mg/dL | Standard Deviation 24.34 |
95% CI: [-23.27, -7.93]
95% CI: [-25.34, -10.05]
95% CI: [-24.14, -8.02]
95% CI: [-32.06, -14.89]
95% CI: [-12.66, 1.02]
95% CI: [-14.76, -1.08]
95% CI: [-13.53, 0.93]
95% CI: [-21.45, -5.94]
Secondary
Change From Baseline in Fasting Plasma Glucose (Week 4).
The change between the value of fasting plasma glucose collected at week 4 and fasting plasma glucose collected at baseline.
Time frame: Baseline and Week 4.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 4). | 8.4 mg/dL | Standard Deviation 30.74 |
| Alogliptin 6.25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 4). | -16.0 mg/dL | Standard Deviation 20.88 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 4). | -20.9 mg/dL | Standard Deviation 19.78 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 4). | -19.0 mg/dL | Standard Deviation 20.64 |
| Alogliptin 50 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 4). | -23.3 mg/dL | Standard Deviation 23.4 |
| Voglibose 0.2 mg TID | Change From Baseline in Fasting Plasma Glucose (Week 4). | -7.2 mg/dL | Standard Deviation 26.77 |
95% CI: [-23.27, -7.93]
95% CI: [-25.34, -10.05]
95% CI: [-24.14, -8.02]
95% CI: [-32.06, -14.89]
95% CI: [-12.66, 1.02]
95% CI: [-14.76, -1.08]
95% CI: [-13.53, 0.93]
95% CI: [-21.45, -5.94]
Secondary
Change From Baseline in Fasting Plasma Glucose (Week 8).
The change between the value of fasting plasma glucose collected at week 8 and fasting plasma glucose collected at baseline.
Time frame: Baseline and Week 8.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 8). | 5.7 mg/dL | Standard Deviation 27.4 |
| Alogliptin 6.25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 8). | -12.0 mg/dL | Standard Deviation 27.77 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 8). | -18.5 mg/dL | Standard Deviation 22.71 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 8). | -18.6 mg/dL | Standard Deviation 20.58 |
| Alogliptin 50 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 8). | -22.6 mg/dL | Standard Deviation 27.6 |
| Voglibose 0.2 mg TID | Change From Baseline in Fasting Plasma Glucose (Week 8). | -3.5 mg/dL | Standard Deviation 28.45 |
95% CI: [-26.52, -8.94]
95% CI: [-32.07, -16.37]
95% CI: [-32.03, -16.65]
95% CI: [-37.04, -19.52]
95% CI: [-17.28, 0.18]
95% CI: [-22.9, -7.18]
95% CI: [-22.9, -7.42]
95% CI: [-27.8, -10.4]
Secondary
Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)).
The change between the value of glucagons collected at week 12 or final visit and glucagons collected at baseline. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and 2 hours after the start of the meal.
Time frame: Baseline and Week 12
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)). | -15.8 pg·hr/mL | Standard Deviation 36.91 |
| Alogliptin 6.25 mg QD | Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)). | -11.5 pg·hr/mL | Standard Deviation 37.45 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)). | -4.5 pg·hr/mL | Standard Deviation 38.54 |
| Alogliptin 25 mg QD | Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)). | -12.6 pg·hr/mL | Standard Deviation 47.23 |
| Alogliptin 50 mg QD | Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)). | -19.5 pg·hr/mL | Standard Deviation 40.47 |
| Voglibose 0.2 mg TID | Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)). | -16.3 pg·hr/mL | Standard Deviation 52.26 |
95% CI: [-7.87, 16.38]
95% CI: [-0.9, 23.42]
95% CI: [-10.56, 16.95]
95% CI: [-16.27, 8.94]
95% CI: [-9.79, 19.29]
95% CI: [-2.67, 26.19]
95% CI: [-12.02, 19.4]
95% CI: [-18.04, 11.71]
Secondary
Change From Baseline in Glycosylated Hemoglobin (Week 2).
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 2 and glycosylated hemoglobin collected at baseline.
Time frame: Baseline and Week 2.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (Week 2). | 0.00 percentage of Glycosylated Hemoglobin | Standard Deviation 0.187 |
| Alogliptin 6.25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 2). | -0.16 percentage of Glycosylated Hemoglobin | Standard Deviation 0.153 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 2). | -0.17 percentage of Glycosylated Hemoglobin | Standard Deviation 0.194 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 2). | -0.16 percentage of Glycosylated Hemoglobin | Standard Deviation 0.187 |
| Alogliptin 50 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 2). | -0.15 percentage of Glycosylated Hemoglobin | Standard Deviation 0.18 |
| Voglibose 0.2 mg TID | Change From Baseline in Glycosylated Hemoglobin (Week 2). | -0.10 percentage of Glycosylated Hemoglobin | Standard Deviation 0.204 |
95% CI: [-0.213, -0.104]
95% CI: [-0.234, -0.114]
95% CI: [-0.219, -0.1]
95% CI: [-0.212, -0.095]
95% CI: [-0.116, -0.003]
95% CI: [-0.136, -0.014]
95% CI: [-0.121, 0]
95% CI: [-0.114, 0.006]
Secondary
Change From Baseline in Glycosylated Hemoglobin (Week 4).
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 4 and glycosylated hemoglobin collected at baseline.
Time frame: Baseline and Week 4.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (Week 4). | -0.01 percentage of Glycosylated Hemoglobin | Standard Deviation 0.336 |
| Alogliptin 6.25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 4). | -0.34 percentage of Glycosylated Hemoglobin | Standard Deviation 0.243 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 4). | -0.38 percentage of Glycosylated Hemoglobin | Standard Deviation 0.309 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 4). | -0.35 percentage of Glycosylated Hemoglobin | Standard Deviation 0.281 |
| Alogliptin 50 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 4). | -0.40 percentage of Glycosylated Hemoglobin | Standard Deviation 0.284 |
| Voglibose 0.2 mg TID | Change From Baseline in Glycosylated Hemoglobin (Week 4). | -0.16 percentage of Glycosylated Hemoglobin | Standard Deviation 0.395 |
95% CI: [-0.419, -0.233]
95% CI: [-0.47, -0.268]
95% CI: [-0.438, -0.241]
95% CI: [-0.485, -0.288]
95% CI: [-0.28, -0.076]
95% CI: [-0.329, -0.112]
95% CI: [-0.299, -0.085]
95% CI: [-0.346, -0.131]
Secondary
Change From Baseline in Glycosylated Hemoglobin (Week 8).
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and glycosylated hemoglobin collected at baseline.
Time frame: Baseline and Week 8.
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (Week 8). | 0.00 percentage of Glycosylated Hemoglobin | Standard Deviation 0.473 |
| Alogliptin 6.25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 8). | -0.50 percentage of Glycosylated Hemoglobin | Standard Deviation 0.432 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 8). | -0.61 percentage of Glycosylated Hemoglobin | Standard Deviation 0.481 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 8). | -0.66 percentage of Glycosylated Hemoglobin | Standard Deviation 0.432 |
| Alogliptin 50 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 8). | -0.69 percentage of Glycosylated Hemoglobin | Standard Deviation 0.382 |
| Voglibose 0.2 mg TID | Change From Baseline in Glycosylated Hemoglobin (Week 8). | -0.17 percentage of Glycosylated Hemoglobin | Standard Deviation 0.634 |
95% CI: [-0.644, -0.356]
95% CI: [-0.763, -0.464]
95% CI: [-0.804, -0.516]
95% CI: [-0.832, -0.559]
95% CI: [-0.494, -0.156]
95% CI: [-0.61, -0.267]
95% CI: [-0.654, -0.315]
95% CI: [-0.683, -0.357]
Secondary
Change From Baseline in Insulin Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC(0-2)).
The change between the value of insulin collected at week 12 or final visit and insulin collected at baseline as measured by the meal tolerance test. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and 2 hours after the start of the meal.
Time frame: Baseline and Week 12
Population: Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Insulin Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC(0-2)). | -3.60 μU·hr/mL | Standard Deviation 12.94 |
| Alogliptin 6.25 mg QD | Change From Baseline in Insulin Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC(0-2)). | -0.74 μU·hr/mL | Standard Deviation 19.745 |
| Alogliptin 12.5 mg QD | Change From Baseline in Insulin Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC(0-2)). | 1.86 μU·hr/mL | Standard Deviation 15.602 |
| Alogliptin 25 mg QD | Change From Baseline in Insulin Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC(0-2)). | 4.12 μU·hr/mL | Standard Deviation 14.057 |
| Alogliptin 50 mg QD | Change From Baseline in Insulin Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC(0-2)). | -1.04 μU·hr/mL | Standard Deviation 23.333 |
| Voglibose 0.2 mg TID | Change From Baseline in Insulin Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC(0-2)). | -15.40 μU·hr/mL | Standard Deviation 20.416 |
95% CI: [-2.736, 8.455]
95% CI: [0.748, 10.165]
95% CI: [3.181, 12.248]
95% CI: [-3.763, 8.877]
95% CI: [7.924, 21.396]
95% CI: [11.353, 23.16]
95% CI: [13.629, 25.401]
95% CI: [7.013, 21.701]