Diabetes Mellitus
Conditions
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
Brief summary
The purpose of this study is to determine the efficacy and safety of alogliptin, once daily (QD), taken in combination with insulin for the treatment of Type 2 Diabetes.
Detailed description
There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% are type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected. Takeda is developing alogliptin (SYR-322) for patients with type 2 diabetes mellitus. Alogliptin is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase 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 dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes. The aim of the current study is to evaluate the efficacy of alogliptin in combination with insulin in subjects who are inadequately controlled on insulin alone (with or without metformin). Individuals who participate in this study will be required to commit to a screening visit and up to 14 additional visits at the study center. Study participation is anticipated to be about 34 weeks (or 8.5 months).
Interventions
DRUGAlogliptin and insulin
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
DRUGInsulin
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 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
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of type 2 diabetes mellitus and currently treated with insulin alone (with or without metformin), and is inadequately controlled. Metformin dose must be stable for at least 8 weeks prior to Randomization. * No treatment with antidiabetic agents other than insulin and metformin within the 8 weeks prior to Randomization. * Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2 * Fasting C-peptide concentration greater than or equal to 0.8 ng per mL. (If this screening criterion is not met, the subject still qualifies if C-peptide greater than or equal to 1.5 ng per mL after a challenge test). * Glycosylated hemoglobin concentration greater than or equal to 8.0% at Screening. * Using a stable dose of insulin of at least 15 units but not more than 100 units per day for at least 8 weeks prior to Randomization. A dose of insulin that varies by up to 15% of the mean will be considered as stable. * If regular use of other, non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening. However, as needed use of prescription or over-the-counter medications is allowed at the discretion of the investigator. * Systolic blood pressure less than or equal to180 mm Hg and diastolic pressure less than or equal to 110 mm Hg * Hemoglobin greater than or equal to 12 g per dL for males and greater than or equal to10 g per dL for females. * Alanine aminotransferase less than or equal to 3 times the upper limit of normal. * Serum creatinine less than or equal to 2.0 mg per dL. * Thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject is clinically euthyroid. * Neither pregnant (confirmed by laboratory testing in females of childbearing potential) nor lactating. * Female subjects of childbearing potential must be practicing adequate contraception. Adequate contraception must be practiced for the duration of participation in the study. * Able and willing to monitor own blood glucose concentrations with a home glucose monitor * No major illness or debility that in the investigator's opinion prohibits the individual from completing the study * Able and willing to provide written informed consent
Exclusion criteria
* Urine albumin to creatinine ratio of greater than 1000 μg per mg at Screening. If elevated, the subject may be rescreened within 1 week. * History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening. (History of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed.). * History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening. * History of treated diabetic gastric paresis. * New York Heart Association Class III or IV heart failure regardless of therapy. Currently treated subjects who are stable at Class I or II are candidates for the study. * History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening. * History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin. * History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus. * History of a psychiatric disorder that will affect ability to participate in the study. * History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors. * History of alcohol or substance abuse within the 2 years prior to Screening. * Receipt of any investigational drug within the 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within the 3 months prior to Screening. * Prior treatment in an investigational study of alogliptin. * Excluded Medications: * Treatment with antidiabetic agents other than insulin and metformin is not allowed within the 8 weeks prior to Randomization and through the completion of the end-of treatment or early termination procedures. (Exception: if has received other antidiabetic therapy for less than 7 days within the 3 months prior to Screening.) * Treatment with weight-loss drugs, any investigational antidiabetics, or oral or systemically injected glucocorticoids is not allowed from 3 months prior to randomization through the completion of the end-of-treatment or early termination procedures. Inhaled corticosteroids are allowed. * Must not take any medications, including over-the-counter products, without first consulting with the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26. | Baseline and Week 26. | 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 26 or final visit and glycosylated hemoglobin collected at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 and Glycosylated Hemoglobin collected at baseline. |
| Change From Baseline in Glycosylated Hemoglobin (Week 16). | Baseline and Week 16. | 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 16 and Glycosylated Hemoglobin collected at baseline. |
| Change From Baseline in Glycosylated Hemoglobin (Week 20). | Baseline and Week 20. | 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 20 and Glycosylated Hemoglobin collected at baseline. |
| Change From Baseline in Fasting Plasma Glucose (Week 1). | Baseline and Week 1. | The change between the value of fasting plasma glucose collected at final visit or week 1 and fasting plasma glucose 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 and fasting plasma glucose collected at baseline. |
| Change From Baseline in Fasting Plasma Glucose (Week 16). | Baseline and Week 16. | The change between the value of fasting plasma glucose collected at week 16 and fasting plasma glucose collected at baseline. |
| Change From Baseline in Fasting Plasma Glucose (Week 20). | Baseline and Week 20. | The change between the value of fasting plasma glucose collected at week 20 and fasting plasma glucose collected at baseline. |
| Change From Baseline in Fasting Plasma Glucose (Week 26). | Baseline and Week 26. | The change between the value of fasting plasma glucose collected at week 26 or final visit and fasting plasma glucose collected at baseline. |
| Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL). | 26 Weeks. | The number of participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during the 26 week study. |
| Number of Participants Requiring Rescue. | 26 Weeks. | The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 26 week study. |
| Change From Baseline in C-peptide (Week 4). | Baseline and Week 4. | The change between the value of C-peptide collected at week 4 and C-peptide collected at baseline. |
| 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 C-peptide (Week 12). | Baseline and Week 12. | The change between the value of C-peptide collected at week 12 and C-peptide collected at baseline. |
| Change From Baseline in C-peptide (Week 16). | Baseline and Week 16. | The change between the value of C-peptide collected at week 16 and C-peptide collected at baseline. |
| Change From Baseline in C-peptide (Week 20). | Baseline and Week 20. | The change between the value of C-peptide collected at week 20 and C-peptide collected at baseline. |
| Change From Baseline in C-peptide (Week 26). | Baseline and Week 26. | The change between the value of C-peptide collected at week 26 or final visit and C-peptide collected at baseline. |
| Number of Participants With Glycosylated Hemoglobin ≤ 6.5%. | Baseline and Week 26. | The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5% during the 26 week study. |
| Number of Participants With Glycosylated Hemoglobin ≤ 7.0%. | Baseline and Week 26. | The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.0% during the 26 week study. |
| Number of Participants With Glycosylated Hemoglobin ≤ 7.5%. | Baseline and Week 26. | The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.5% during the 26 week study. |
| Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%. | Baseline and Week 26. | The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5% during the 26 week study. |
| Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%. | Baseline and Week 26. | The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.0% during the 26 week study. |
| Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%. | Baseline and Week 26. | The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.5% during the 26 week study. |
| Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%. | Baseline and Week 26. | The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 2.0% during the 26 week study. |
| Change From Baseline in Body Weight (Week 8). | Baseline and Week 8. | The change between Body Weight measured at week 8 and Body Weight measured at baseline. |
| Change From Baseline in Body Weight (Week 12). | Baseline and Week 12. | The change between Body Weight measured at week 12 and Body Weight measured at baseline. |
| Change From Baseline in Body Weight (Week 20). | Baseline and Week 20. | The change between Body Weight measured at week 20 and Body Weight measured at baseline. |
| Change From Baseline in Body Weight (Week 26). | Baseline and Week 26. | The change between Body Weight measured at week 26 or final visit and Body Weight measured at baseline. |
| Change From Baseline in C-peptide (Week 8). | Baseline and Week 8. | The change between the value of C-peptide collected at week 8 and C-peptide collected at baseline. |
Countries
Argentina, Australia, Brazil, Chile, Czechia, Germany, Guatemala, Hungary, India, Mexico, Netherlands, New Zealand, Peru, Poland, South Africa, United States
Participant flow
Recruitment details
Participants enrolled at 110 investigative sites in Australia, Brazil, Chile, Guatemala, Germany, Hungary, India, Mexico, New Zealand, the Netherlands, Poland, South Africa, and the United States from 16 March 2006 to 18 September 2006
Pre-assignment details
Participants with a historical diagnosis of type 2 diabetes mellitus who were inadequately controlled while being treated with insulin with or without metformin were enrolled in one of three, once-daily (QD) treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks. | 130 |
| Alogliptin 12.5 mg QD Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks. | 131 |
| Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks. | 129 |
| Total | 390 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative Decision | 0 | 1 | 0 |
| Overall Study | Administrative Error | 1 | 1 | 1 |
| Overall Study | Adverse Event | 4 | 1 | 6 |
| Overall Study | Lack of Efficacy | 52 | 27 | 25 |
| Overall Study | Lost to Follow-up | 2 | 4 | 3 |
| Overall Study | Physician Decision | 10 | 7 | 7 |
| Overall Study | Protocol Violation | 3 | 5 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 6 |
Baseline characteristics
| Characteristic | Placebo | Alogliptin 12.5 mg QD | Alogliptin 25 mg QD | Total |
|---|---|---|---|---|
| Age, Customized <65 years | 109 participants | 112 participants | 106 participants | 327 participants |
| Age, Customized ≥65 years | 21 participants | 19 participants | 23 participants | 63 participants |
| Sex: Female, Male Female | 68 Participants | 76 Participants | 85 Participants | 229 Participants |
| Sex: Female, Male Male | 62 Participants | 55 Participants | 44 Participants | 161 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 54 / 129 | 58 / 131 | 50 / 129 |
| serious Total, serious adverse events | 6 / 129 | 8 / 131 | 7 / 129 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26.
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 26 or final visit and glycosylated hemoglobin collected at baseline.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF). ANCOVA = Analysis of covariance.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26. | -0.13 percentage of Glycosylated Hemoglobin | Standard Error 0.077 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26. | -0.63 percentage of Glycosylated Hemoglobin | Standard Error 0.076 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26. | -0.71 percentage of Glycosylated Hemoglobin | Standard Error 0.078 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 26. For comparison of either alogliptin dose vs. placebo (2-sample t test), study sample size \>=390 participants had 95% power to detect a treatment difference as small as 0.4% in the per protocol analysis set assuming a standard deviation of 0.8%, a 2-sided test at 0.05 significance level and \>=80% of subjects meeting the per protocol criteria.p-value: <0.00195% CI: [-0.72, -0.3]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 26. For comparison of either alogliptin dose vs. placebo (2-sample t test), study sample size \>=390 participants had 95% power to detect a treatment difference as small as 0.4% in the per protocol analysis set assuming a standard deviation of 0.8%, a 2-sided test at 0.05 significance level and \>=80% of subjects meeting the per protocol criteria.p-value: <0.00195% CI: [-0.8, -0.37]ANCOVA
Secondary
Change From Baseline in Body Weight (Week 12).
The change between Body Weight measured at week 12 and Body Weight measured at baseline.
Time frame: Baseline and Week 12.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight (Week 12). | 0.50 kg | Standard Error 0.221 |
| Alogliptin 12.5 mg QD | Change From Baseline in Body Weight (Week 12). | 0.44 kg | Standard Error 0.215 |
| Alogliptin 25 mg QD | Change From Baseline in Body Weight (Week 12). | 0.31 kg | Standard Error 0.219 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.84195% CI: [-0.67, 0.55]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.55695% CI: [-0.8, 0.43]ANCOVA
Secondary
Change From Baseline in Body Weight (Week 20).
The change between Body Weight measured at week 20 and Body Weight measured at baseline.
Time frame: Baseline and Week 20.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight (Week 20). | 0.73 kg | Standard Error 0.231 |
| Alogliptin 12.5 mg QD | Change From Baseline in Body Weight (Week 20). | 0.55 kg | Standard Error 0.225 |
| Alogliptin 25 mg QD | Change From Baseline in Body Weight (Week 20). | 0.45 kg | Standard Error 0.229 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.58695% CI: [-0.81, 0.46]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.40495% CI: [-0.91, 0.37]ANCOVA
Secondary
Change From Baseline in Body Weight (Week 26).
The change between Body Weight measured at week 26 or final visit and Body Weight measured at baseline.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight (Week 26). | 0.63 kg | Standard Error 0.244 |
| Alogliptin 12.5 mg QD | Change From Baseline in Body Weight (Week 26). | 0.68 kg | Standard Error 0.237 |
| Alogliptin 25 mg QD | Change From Baseline in Body Weight (Week 26). | 0.60 kg | Standard Error 0.241 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.87495% CI: [-0.62, 0.72]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.94895% CI: [-0.7, 0.65]ANCOVA
Secondary
Change From Baseline in Body Weight (Week 8).
The change between Body Weight measured at week 8 and Body Weight measured at baseline.
Time frame: Baseline and Week 8.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight (Week 8). | 0.39 kg | Standard Error 0.191 |
| Alogliptin 12.5 mg QD | Change From Baseline in Body Weight (Week 8). | 0.10 kg | Standard Error 0.185 |
| Alogliptin 25 mg QD | Change From Baseline in Body Weight (Week 8). | 0.18 kg | Standard Error 0.189 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.29195% CI: [-0.81, 0.24]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.43995% CI: [-0.74, 0.32]ANCOVA
Secondary
Change From Baseline in C-peptide (Week 12).
The change between the value of C-peptide collected at week 12 and C-peptide collected at baseline.
Time frame: Baseline and Week 12.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in C-peptide (Week 12). | 0.207 ng/mL | Standard Error 0.1558 |
| Alogliptin 12.5 mg QD | Change From Baseline in C-peptide (Week 12). | 0.333 ng/mL | Standard Error 0.1521 |
| Alogliptin 25 mg QD | Change From Baseline in C-peptide (Week 12). | 0.390 ng/mL | Standard Error 0.1553 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.56295% CI: [-0.302, 0.554]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.40795% CI: [-0.251, 0.616]ANCOVA
Secondary
Change From Baseline in C-peptide (Week 16).
The change between the value of C-peptide collected at week 16 and C-peptide collected at baseline.
Time frame: Baseline and Week 16.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in C-peptide (Week 16). | 0.241 ng/mL | Standard Error 0.1536 |
| Alogliptin 12.5 mg QD | Change From Baseline in C-peptide (Week 16). | 0.319 ng/mL | Standard Error 0.15 |
| Alogliptin 25 mg QD | Change From Baseline in C-peptide (Week 16). | 0.396 ng/mL | Standard Error 0.1532 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.71695% CI: [-0.344, 0.5]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.47495% CI: [-0.272, 0.583]ANCOVA
Secondary
Change From Baseline in C-peptide (Week 20).
The change between the value of C-peptide collected at week 20 and C-peptide collected at baseline.
Time frame: Baseline and Week 20.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in C-peptide (Week 20). | 0.239 ng/mL | Standard Error 0.1467 |
| Alogliptin 12.5 mg QD | Change From Baseline in C-peptide (Week 20). | 0.318 ng/mL | Standard Error 0.1432 |
| Alogliptin 25 mg QD | Change From Baseline in C-peptide (Week 20). | 0.281 ng/mL | Standard Error 0.1463 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.795% CI: [-0.324, 0.482]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.83995% CI: [-0.366, 0.45]ANCOVA
Secondary
Change From Baseline in C-peptide (Week 26).
The change between the value of C-peptide collected at week 26 or final visit and C-peptide collected at baseline.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in C-peptide (Week 26). | -0.083 ng/mL | Standard Error 0.1192 |
| Alogliptin 12.5 mg QD | Change From Baseline in C-peptide (Week 26). | 0.199 ng/mL | Standard Error 0.1164 |
| Alogliptin 25 mg QD | Change From Baseline in C-peptide (Week 26). | 0.042 ng/mL | Standard Error 0.1189 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.09195% CI: [-0.045, 0.61]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.45995% CI: [-0.207, 0.457]ANCOVA
Secondary
Change From Baseline in C-peptide (Week 4).
The change between the value of C-peptide collected at week 4 and C-peptide collected at baseline.
Time frame: Baseline and Week 4.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in C-peptide (Week 4). | -0.023 ng/mL | Standard Error 0.1062 |
| Alogliptin 12.5 mg QD | Change From Baseline in C-peptide (Week 4). | 0.132 ng/mL | Standard Error 0.1001 |
| Alogliptin 25 mg QD | Change From Baseline in C-peptide (Week 4). | 0.453 ng/mL | Standard Error 0.1014 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-Peptide at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.28695% CI: [-0.131, 0.443]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.00195% CI: [0.188, 0.765]ANCOVA
Secondary
Change From Baseline in C-peptide (Week 8).
The change between the value of C-peptide collected at week 8 and C-peptide collected at baseline.
Time frame: Baseline and Week 8.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in C-peptide (Week 8). | -0.024 ng/mL | Standard Error 0.1224 |
| Alogliptin 12.5 mg QD | Change From Baseline in C-peptide (Week 8). | 0.178 ng/mL | Standard Error 0.118 |
| Alogliptin 25 mg QD | Change From Baseline in C-peptide (Week 8). | 0.348 ng/mL | Standard Error 0.122 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-Peptide at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.23695% CI: [-0.132, 0.536]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-Peptide at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.03295% CI: [0.032, 0.712]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (Week 1).
The change between the value of fasting plasma glucose collected at final visit or week 1 and fasting plasma glucose collected at baseline.
Time frame: Baseline and Week 1.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 1. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 1). | 6.3 mg/dL | Standard Error 5.4 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 1). | -5.0 mg/dL | Standard Error 5.07 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 1). | -9.9 mg/dL | Standard Error 5.33 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 1. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.12895% CI: [-25.9, 3.3]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 1. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.03495% CI: [-31.1, -1.2]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (Week 12).
The change between the value of fasting plasma glucose collected at week 12 and fasting plasma glucose collected at baseline.
Time frame: Baseline and Week 12.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 12). | -1.4 mg/dL | Standard Error 5.47 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 12). | -5.2 mg/dL | Standard Error 5.38 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 12). | -2.9 mg/dL | Standard Error 5.47 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.62495% CI: [-18.9, 11.3]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.85395% CI: [-16.7, 13.8]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (Week 16).
The change between the value of fasting plasma glucose collected at week 16 and fasting plasma glucose collected at baseline.
Time frame: Baseline and Week 16.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 16). | 4.6 mg/dL | Standard Error 5.38 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 16). | -5.3 mg/dL | Standard Error 5.29 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 16). | -6.3 mg/dL | Standard Error 5.38 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.1995% CI: [-24.7, 4.9]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 16. The treatment effect was be evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.15495% CI: [-25.8, 4.1]ANCOVA
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: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 2. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 2). | 1.0 mg/dL | Standard Error 5.09 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 2). | -3.1 mg/dL | Standard Error 4.84 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 2). | -11.4 mg/dL | Standard Error 5.03 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 2. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.56395% CI: [-17.9, 9.7]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 2. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.08495% CI: [-26.4, 1.7]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (Week 20).
The change between the value of fasting plasma glucose collected at week 20 and fasting plasma glucose collected at baseline.
Time frame: Baseline and Week 20.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 20). | 8.6 mg/dL | Standard Error 5.45 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 20). | -4.2 mg/dL | Standard Error 5.36 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 20). | -11.3 mg/dL | Standard Error 5.46 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.09795% CI: [-27.8, 2.3]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.0195% CI: [-35.1, -4.7]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (Week 26).
The change between the value of fasting plasma glucose collected at week 26 or final visit and fasting plasma glucose collected at baseline.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 26). | 5.8 mg/dL | Standard Error 5.69 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 26). | 2.3 mg/dL | Standard Error 5.59 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 26). | -11.7 mg/dL | Standard Error 5.69 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.66295% CI: [-19.2, 12.2]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.0395% CI: [-33.4, -1.7]ANCOVA
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: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 4). | 5.3 mg/dL | Standard Error 5.28 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 4). | -5.0 mg/dL | Standard Error 5.08 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 4). | -12.1 mg/dL | Standard Error 5.28 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.1695% CI: [-24.7, 4.1]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.0295% CI: [-32.1, -2.8]ANCOVA
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: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (Week 8). | 5.4 mg/dL | Standard Error 5.42 |
| Alogliptin 12.5 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 8). | -13.5 mg/dL | Standard Error 5.26 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose (Week 8). | -14.1 mg/dL | Standard Error 5.39 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 8. The treatment effect was be evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.01395% CI: [-33.7, -4]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: 0.01195% CI: [-34.5, -4.5]ANCOVA
Secondary
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 and Glycosylated Hemoglobin collected at baseline.
Time frame: Baseline and Week 12.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (Week 12). | -0.27 percentage of Glycosylated Hemoglobin | Standard Error 0.073 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 12). | -0.84 percentage of Glycosylated Hemoglobin | Standard Error 0.072 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 12). | -0.81 percentage of Glycosylated Hemoglobin | Standard Error 0.073 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: <0.00195% CI: [-0.77, -0.37]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: <0.00195% CI: [-0.75, -0.34]ANCOVA
Secondary
Change From Baseline in Glycosylated Hemoglobin (Week 16).
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 16 and Glycosylated Hemoglobin collected at baseline.
Time frame: Baseline and Week 16.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (Week 16). | -0.22 percentage of Glycosylated Hemoglobin | Standard Error 0.076 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 16). | -0.80 percentage of Glycosylated Hemoglobin | Standard Error 0.074 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 16). | -0.76 percentage of Glycosylated Hemoglobin | Standard Error 0.076 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: <0.00195% CI: [-0.79, -0.37]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: <0.00195% CI: [-0.75, -0.33]ANCOVA
Secondary
Change From Baseline in Glycosylated Hemoglobin (Week 20).
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 20 and Glycosylated Hemoglobin collected at baseline.
Time frame: Baseline and Week 20.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (Week 20). | -0.17 percentage of Glycosylated Hemoglobin | Standard Error 0.078 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 20). | -0.76 percentage of Glycosylated Hemoglobin | Standard Error 0.076 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 20). | -0.74 percentage of Glycosylated Hemoglobin | Standard Error 0.078 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: <0.00195% CI: [-0.8, -0.37]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: <0.00195% CI: [-0.79, -0.35]ANCOVA
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: Randomized participants who received at least 1 dose of study drug and who had an HbA1c measurement at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (Week 4). | -0.26 percentage of Glycosylated Hemoglobin | Standard Error 0.045 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 4). | -0.47 percentage of Glycosylated Hemoglobin | Standard Error 0.045 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 4). | -0.58 percentage of Glycosylated Hemoglobin | Standard Error 0.045 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: <0.00195% CI: [-0.34, -0.09]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: <0.00195% CI: [-0.45, -0.2]ANCOVA
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: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (Week 8). | -0.27 percentage of Glycosylated Hemoglobin | Standard Error 0.061 |
| Alogliptin 12.5 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 8). | -0.76 percentage of Glycosylated Hemoglobin | Standard Error 0.06 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin (Week 8). | -0.84 percentage of Glycosylated Hemoglobin | Standard Error 0.062 |
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: <0.00195% CI: [-0.65, -0.31]ANCOVA
Comparison: The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.p-value: <0.00195% CI: [-0.73, -0.39]ANCOVA
Secondary
Number of Participants Requiring Rescue.
The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 26 week study.
Time frame: 26 Weeks.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who completed at least 1 study visit after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Requiring Rescue. | 52 participants |
| Alogliptin 12.5 mg QD | Number of Participants Requiring Rescue. | 27 participants |
| Alogliptin 25 mg QD | Number of Participants Requiring Rescue. | 25 participants |
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants requiring rescue. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: <0.00195% CI: [0.198, 0.619]Regression, Logistic
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants requiring rescue. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: <0.00195% CI: [0.189, 0.608]Regression, Logistic
Secondary
Number of Participants With Glycosylated Hemoglobin ≤ 6.5%.
The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5% during the 26 week study.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who completed at least 1 HbA1c measurement after baseline.~Due to no participants in the placebo arm achieved HbA1c ≤ 6.5%, the odds ratio of alogliptin to placebo and 95% CI were not estimable from the logistic regression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Glycosylated Hemoglobin ≤ 6.5%. | 0 participants |
| Alogliptin 12.5 mg QD | Number of Participants With Glycosylated Hemoglobin ≤ 6.5%. | 3 participants |
| Alogliptin 25 mg QD | Number of Participants With Glycosylated Hemoglobin ≤ 6.5%. | 3 participants |
Secondary
Number of Participants With Glycosylated Hemoglobin ≤ 7.0%.
The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.0% during the 26 week study.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Glycosylated Hemoglobin ≤ 7.0%. | 1 participants |
| Alogliptin 12.5 mg QD | Number of Participants With Glycosylated Hemoglobin ≤ 7.0%. | 11 participants |
| Alogliptin 25 mg QD | Number of Participants With Glycosylated Hemoglobin ≤ 7.0%. | 10 participants |
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: 0.01695% CI: [1.589, 100.682]Regression, Logistic
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo was evaluated inferentially with a Wald test at the 0.05 significance levelp-value: 0.02395% CI: [1.401, 90.379]Regression, Logistic
Secondary
Number of Participants With Glycosylated Hemoglobin ≤ 7.5%.
The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.5% during the 26 week study.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Glycosylated Hemoglobin ≤ 7.5%. | 5 participants |
| Alogliptin 12.5 mg QD | Number of Participants With Glycosylated Hemoglobin ≤ 7.5%. | 22 participants |
| Alogliptin 25 mg QD | Number of Participants With Glycosylated Hemoglobin ≤ 7.5%. | 33 participants |
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: <0.00195% CI: [2.047, 16.305]ANCOVA
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: <0.00195% CI: [3.54, 27.039]Regression, Logistic
Secondary
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%.
The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5% during the 26 week study.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%. | 40 participants |
| Alogliptin 12.5 mg QD | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%. | 70 participants |
| Alogliptin 25 mg QD | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%. | 70 participants |
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥0.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: <0.00195% CI: [1.579, 4.53]Regression, Logistic
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥0.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: <0.00195% CI: [1.653, 4.808]Regression, Logistic
Secondary
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%.
The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.0% during the 26 week study.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%. | 17 participants |
| Alogliptin 12.5 mg QD | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%. | 41 participants |
| Alogliptin 25 mg QD | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%. | 47 participants |
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: <0.00195% CI: [1.651, 6.06]Regression, Logistic
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: <0.00195% CI: [2.083, 7.64]Regression, Logistic
Secondary
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%.
The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.5% during the 26 week study.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%. | 6 participants |
| Alogliptin 12.5 mg QD | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%. | 22 participants |
| Alogliptin 25 mg QD | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%. | 23 participants |
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: 0.00295% CI: [1.732, 11.953]Regression, Logistic
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: 0.00295% CI: [1.74, 12.052]Regression, Logistic
Secondary
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%.
The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 2.0% during the 26 week study.
Time frame: Baseline and Week 26.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.~Due to no participants in the placebo arm achieved HbA1c decrease from baseline ≥2.0%, the odds ratio of alogliptin to placebo and 95% CI were not estimable from the logistic regression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%. | 0 participants |
| Alogliptin 12.5 mg QD | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%. | 11 participants |
| Alogliptin 25 mg QD | Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%. | 11 participants |
Secondary
Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL).
The number of participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during the 26 week study.
Time frame: 26 Weeks.
Population: Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 fasting plasma glucose measurement after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL). | 105 participants |
| Alogliptin 12.5 mg QD | Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL). | 99 participants |
| Alogliptin 25 mg QD | Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL). | 86 participants |
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants with marked hyperglycemia. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: 0.07595% CI: [0.286, 1.063]Regression, Logistic
Comparison: The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants with marked hyperglycemia. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.p-value: 0.00295% CI: [0.191, 0.695]Regression, Logistic