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Safety and Efficacy Study of Alogliptin on Glycemic Control in Subjects With Type 2 Diabetes.

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT00755846
Collaborator
(none)
265
Enrollment
6
Arms
7
Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and efficacy of alogliptin, once daily (QD), compared to diet and exercise, sulfonylurea, metformin and a combination of sulfonylurea and metformin for treating subjects with type 2 diabetes.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Of the approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, 90% to 95% have type 2 diabetes mellitus. The prevalence of type 2 diabetes mellitus varies among racial and ethnic populations and has been shown to increase with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a disproportionate increase in the elderly population will result in a marked increase in diabetic patients, placing an ever-increasing burden on families and the health care system.

In response to this problem, Takeda Global Research & Development Center, Inc. is developing SYR-322 (alogliptin), a selective, orally available inhibitor of the enzyme dipeptidyl peptidase IV. Dipeptidyl peptidase IV is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide.

Individuals who want to participate in this study will be required to provide written informed consent. Study participation is anticipated to be about 14 Weeks. Multiple procedures will occur at each visit which may include blood collection, urine collection, vital signs including sitting and standing blood pressure and pulse, body height and weight, physical examinations and electrocardiograms.

Study Design

Study Type:
Interventional
Actual Enrollment :
265 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Comparison Study to Determine the Efficacy and Safety of SYR110322 in Patients With Type 2 Diabetes, Who Are Either Receiving No Current Treatment or Currently Treated With Diet and Exercise, Sulfonylurea, Metformin or a Combination of Sulfonylurea and Metformin
Study Start Date :
Mar 1, 2005
Actual Primary Completion Date :
Oct 1, 2005
Actual Study Completion Date :
Oct 1, 2005

Arms and Interventions

Arm Intervention/Treatment
Experimental: Alogliptin 6.25 mg QD

Drug: Alogliptin
Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks
Other Names:
  • SYR-322
  • SYR110322

    		•
    Experimental: Alogliptin 12.5 mg QD

    Drug: Alogliptin
    Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks.
    Other Names:
  • SYR-322
  • SYR110322

    		•
    Experimental: Alogliptin 25 mg QD

    Drug: Alogliptin
    Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks.
    Other Names:
  • SYR-322
  • SYR110322

    		•
    Experimental: Alogliptin 50 mg QD

    Drug: Alogliptin
    Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks.
    Other Names:
  • SYR-322
  • SYR110322

    		•
    Experimental: Alogliptin 100 mg QD

    Drug: Alogliptin
    Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Other Names:
  • SYR-322
  • SYR110322

    		•
    Placebo Comparator: Placebo QD

    Drug: Placebo
    Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Day 85. [Baseline and Day 85.]

      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 day 85 or final visit and glycosylated hemoglobin collected at baseline.

    Secondary Outcome Measures

    1. Change From Baseline in Glycosylated Hemoglobin at Day 43. [Baseline and Day 43.]

      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 day 43 and glycosylated hemoglobin collected at baseline.

    2. Change From Baseline in Fasting Plasma Glucose (Day 43). [Baseline and Day 43]

      The change between the value of fasting plasma glucose collected at day 43 and fasting plasma glucose collected at baseline.

    3. Change From Baseline in Fasting Plasma Glucose (Day 85). [Baseline and Day 85.]

      The change between the value of fasting plasma glucose collected at day 85 or final visit and fasting plasma glucose collected at baseline.

    4. Change From Baseline in Fasting Fructosamine (Day 43). [Baseline and Day 43.]

      The change between the value of fasting fructosamine collected at day 43 and fasting fructosamine collected at baseline.

    5. Change From Baseline in Fasting Fructosamine (Day 85). [Baseline and Day 85.]

      The change between the value of fasting fructosamine collected at day 85 or final visit and fasting fructosamine collected at baseline.

    6. Change From Baseline in Total Cholesterol (Day 43). [Baseline and Day 43]

      The change between the value of cholesterol collected at day 43 and cholesterol collected at baseline.

    7. Change From Baseline in Total Cholesterol (Day 85). [Baseline and Day 85.]

      The change between the value of cholesterol collected at day 85 or final visit and cholesterol collected at baseline.

    8. Change From Baseline in High-Density Lipoprotein Cholesterol (Day 43). [Baseline and Day 43.]

      The change between high-density lipoprotein cholesterol collected at day 43 and high-density lipoprotein cholesterol collected at baseline.

    9. Change From Baseline in High-Density Lipoprotein Cholesterol (Day 85). [Baseline and Day 85.]

      The change between high-density lipoprotein cholesterol collected at day 85 or final visit and high-density lipoprotein cholesterol collected at baseline.

    10. Change From Baseline in Low-Density Lipoprotein Cholesterol (Day 43). [Baseline and Day 43.]

      The change between low-density lipoprotein cholesterol collected at day 43 and low-density lipoprotein cholesterol collected at baseline.

    11. Change From Baseline in Low-Density Lipoprotein Cholesterol (Day 85). [Baseline and Day 85.]

      The change between low-density lipoprotein cholesterol collected at day 85 or final visit and low-density lipoprotein cholesterol collected at baseline.

    12. Change From Baseline in Triglycerides (Day 43). [Baseline and Day 43.]

      The change between triglycerides collected at day 43 and triglycerides collected at baseline.

    13. Change From Baseline in Triglycerides (Day 85). [Baseline and Day 85.]

      The change between triglycerides collected at day 85 or final visit and triglycerides collected at baseline.

    14. Mean Percent Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg/dL). [85 Days.]

      The incidence of marked hyperglycemia occurring in participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during study. Overall mean obtained by weighting the hyperglycemia percent incidence values at each time point by number of days in between visits. Mean percent incidence of marked hyperglycemia at each time point is the percent of self-monitored blood glucose measurements greater than or equal to 200 mg per dL, calculated per participant and then averaged across population.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Has type 2 diabetes mellitus and were either receiving no current treatment or currently treated with a sulfonylurea, metformin, or a combination of a sulfonylurea and metformin but experiencing inadequate glycemic control. Subjects qualified as receiving no current treatment if 1 of the following conditions applied:

    • Subject was newly diagnosed (ie, had not received any treatment).

    • Subject was treated with diet and exercise alone for the 3 months prior to Screening

    • Subject had received <7 continuous days of any antidiabetic therapy within the 3 months prior to Screening.

    • Subject had a diagnosis of type 2 diabetes mellitus based on current American Diabetes Association criteria: fasting plasma glucose ≥126 mg/dL, oral glucose tolerance test at 2 hours after administration of the glucose load must have been ≥200 mg/dL, or symptoms of diabetes plus casual plasma glucose ≥200 mg/dL.

    • Body mass index ≥23 kg/m2 and ≤40 kg/m2.

    • Fasting C-peptide concentration ≥0.8 ng/mL.

    • Glycosylated hemoglobin concentration between 6.8% and 11.0%.

    • Fasting plasma glucose >126 mg/dL at Screening.

    • No treatment within the 3 months prior to Screening with any other agents known to have effects on glucose (other than as described above, a sulfonylurea, metformin, or a combination of a sulfonylurea and metformin in subjects on antidiabetics), including but not limited to the following:

    • Other antidiabetic agents

    • Investigational antidiabetic agents

    • Niacin

    • Regular use of systemic glucocorticoids.

    • No treatment within the 3 months prior to Screening with weight-loss drugs

    • If taking other non-excluded medications, must have been on a stable dose of medication for at least 4 weeks.

    • Diastolic blood pressure ≤110 mm Hg and a systolic pressure of ≤180 mm Hg.

    • Female subjects could neither be pregnant (confirmed by laboratory testing) nor lactating, and if of childbearing potential must have been practicing adequate contraception.

    • Able and willing to monitor their own blood glucose concentrations with a home glucose monitor.

    • No major illness or debility that in the investigator's opinion prohibited the subject from completing the study.

    • Hemoglobin ≥12 g/dL for males and ≥10 g/dL for females.

    • Hepatic transaminase ≤2 x upper limit of normal.

    Exclusion Criteria:

    • History of cancer, other than squamous cell or basal cell carcinoma of the skin, that had not been in full remission for at least 1 year prior to Screening.

    • History of proteinuria >1000 mg/day on a 12- or 24-hour urine collection OR a urine albumin/creatinine ratio >1000 μg/mg at Screening. If elevated, the subject was to be rescreened within 1 week.

    • Serum creatinine ≥2.0 mg/dL.

    • History of proliferative diabetic retinopathy OR any history of laser-treated retinopathy.

    • History of treated peripheral or autonomic neuropathy.

    • History of systolic dysfunction congestive heart failure.

    • History of myocardial infarction within 1 year prior to Screening.

    • History of ulcerative colitis or Crohn's disease.

    • History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.

    • History of a psychiatric disorder that would affect the subject's ability to participate in the study.

    • History of anaphylactic reaction(s) to any drug.

    • History of angioedema.

    • History of alcohol or substance abuse within the last 2 years.

    • History of any surgery that could potentially affect the absorption of the study drug.

    • Receipt of any investigational drug within the preceding 30 days or a history of receipt of an investigational antidiabetic drug within the preceding 90 days.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Director: VP Biological Sciences, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT00755846
    Other Study ID Numbers:
    • SYR-322-003
    • U1111-1113-8352
    First Posted:
    Sep 19, 2008
    Last Update Posted:
    Feb 3, 2012
    Last Verified:
    Feb 1, 2012
    Keywords provided by Takeda
    Diabetes Mellitus
    Drug Therapy
    Diabetes Mellitus, Type II
    Type 2 Diabetes Mellitus
    Hyperinsulinism
    Insulin Resistance
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Alogliptin

    Study Results

    Participant Flow

    Recruitment Details Participants enrolled at 62 sites in Chile and the United States from 17 March 2005 to 10 June 2005.
    Pre-assignment Detail Participants with a historical diagnosis of type 2 diabetes mellitus who were either receiving no current treatment or currently treated with diet and exercise, a sulfonylurea, metformin, or a combination of a sulfonylurea and metformin enrolled in once daily (QD) groups.
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Period Title: Overall Study
    STARTED 43 44 44 45 44 45
    COMPLETED 18 27 32 32 27 31
    NOT COMPLETED 25 17 12 13 17 14

    Baseline Characteristics

    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD Total
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks. Total of all reporting groups
    Overall Participants 43 44 44 45 44 45 265
    Age, Customized (participants) [Number]
    <65 years
    33
    76.7%
    38
    86.4%
    33
    75%
    36
    80%
    31
    70.5%
    34
    75.6%
    205
    77.4%
    ≥65 years
    10
    23.3%
    6
    13.6%
    11
    25%
    9
    20%
    13
    29.5%
    11
    24.4%
    60
    22.6%
    Sex: Female, Male (Count of Participants)
    Female
    24
    55.8%
    25
    56.8%
    22
    50%
    17
    37.8%
    26
    59.1%
    25
    55.6%
    139
    52.5%
    Male
    19
    44.2%
    19
    43.2%
    22
    50%
    28
    62.2%
    18
    40.9%
    20
    44.4%
    126
    47.5%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Day 85.
    Description 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 day 85 or final visit and glycosylated hemoglobin collected at baseline.
    Time Frame Baseline and Day 85.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 85. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 41 42 42 45 43 44
    Least Squares Mean (Standard Error) [percentage of Glycosylated Hemoglobin]
    -0.01
    (0.135)
    -0.19
    (0.121)
    -0.54
    (0.122)
    -0.56
    (0.117)
    -0.44
    (0.124)
    -0.51
    (0.119)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance has at least 98% power to detect a treatment difference (all active versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and body mass index (BMI), diabetes duration and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.43
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.135
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has 90% power to detect a treatment difference (each active dose versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments A step-down sequential approach was used to test the hypothesis that the treatment coefficient in the model is 0 for each of the five individual active treatment groups vs. placebo.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.50
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.171
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has 90% power to detect a treatment difference (each active dose versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments A step-down sequential approach was used to test the hypothesis that the treatment coefficient in the model is 0 for each of the five individual active treatment groups vs. placebo.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.42
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.176
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has 90% power to detect a treatment difference (each active dose versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments A step-down sequential approach was used to test the hypothesis that the treatment coefficient in the model is 0 for each of the five individual active treatment groups vs. placebo.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.55
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.170
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has 90% power to detect a treatment difference (each active dose versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments A step-down sequential approach was used to test the hypothesis that the treatment coefficient in the model is 0 for each of the five individual active treatment groups vs. placebo.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.52
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.174
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has 90% power to detect a treatment difference (each active dose versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.307
    Comments A step-down sequential approach was used to test the hypothesis that the treatment coefficient in the model is 0 for each of the five individual active treatment groups vs. placebo.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.18
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.173
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    2. Secondary Outcome
    Title Change From Baseline in Glycosylated Hemoglobin at Day 43.
    Description 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 day 43 and glycosylated hemoglobin collected at baseline.
    Time Frame Baseline and Day 43.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to treat), and who had measurements at baseline and at Day 43. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 41 42 42 44 43 44
    Least Squares Mean (Standard Error) [percentage of Glycosylated Hemoglobin]
    0.02
    (0.097)
    -0.12
    (0.095)
    -0.35
    (0.096)
    -0.36
    (0.093)
    -0.32
    (0.097)
    -0.31
    (0.094)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has at least 98% power to detect a treatment difference (all active versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.31
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.106
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has 90% power to detect a treatment difference (each active dose versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.32
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.134
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has 90% power to detect a treatment difference (each active dose versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.016
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.34
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.138
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has 90% power to detect a treatment difference (each active dose versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.38
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.134
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has 90% power to detect a treatment difference (each active dose versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.37
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.137
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c. With at least 234 patients, a two-group t-test with a 0.05 two-sided significance level has 90% power to detect a treatment difference (each active dose versus placebo) in HbA1c change from baseline as small as 0.55%, assuming a common standard deviation of 0.7%.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.321
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.14
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.136
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    3. Secondary Outcome
    Title Change From Baseline in Fasting Plasma Glucose (Day 43).
    Description The change between the value of fasting plasma glucose collected at day 43 and fasting plasma glucose collected at baseline.
    Time Frame Baseline and Day 43

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 43. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 41 42 42 45 43 44
    Least Squares Mean (Standard Error) [mg/dL]
    4.9
    (6.09)
    -7.3
    (6.00)
    -11.5
    (6.02)
    -24.5
    (5.80)
    -17.9
    (6.10)
    -25.6
    (5.88)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting plasma glucose (FPG). The treatment effect was evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and body mass index (BMI), diabetes duration, and baseline FPG as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -22.2
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.65
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline FPG as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -30.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.40
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline FPG as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -22.8
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.68
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline FPG as covariates
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -29.4
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.38
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.057
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline FPG as covariates
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -16.4
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.57
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.156
    Comments No multiplicity adjustments
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline FPG as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.2
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.56
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    4. Secondary Outcome
    Title Change From Baseline in Fasting Plasma Glucose (Day 85).
    Description The change between the value of fasting plasma glucose collected at day 85 or final visit and fasting plasma glucose collected at baseline.
    Time Frame Baseline and Day 85.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 85. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 41 42 42 45 43 44
    Least Squares Mean (Standard Error) [mg/dL]
    8.5
    (6.45)
    -7.8
    (6.36)
    -5.1
    (6.39)
    -27.0
    (6.14)
    -16.1
    (6.47)
    -20.9
    (6.23)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between all doses of alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline FPG as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -23.9
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.05
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline FPG as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -29.4
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.91
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline FPG as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -24.6
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.20
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and body mass index, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -35.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.88
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.136
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.6
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.09
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.073
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HbA1c as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -16.3
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.07
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    5. Secondary Outcome
    Title Change From Baseline in Fasting Fructosamine (Day 43).
    Description The change between the value of fasting fructosamine collected at day 43 and fasting fructosamine collected at baseline.
    Time Frame Baseline and Day 43.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 43. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 39 41 42 43 39 43
    Least Squares Mean (Standard Error) [mg/dL]
    7.6
    (5.35)
    -4.2
    (5.16)
    -13.1
    (5.12)
    -14.5
    (5.05)
    -16.3
    (5.47)
    -11.7
    (5.09)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect will be evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -19.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.85
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -19.2
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.37
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -23.8
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.71
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -22.1
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.33
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -20.7
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.44
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.117
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.7
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.45
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    6. Secondary Outcome
    Title Change From Baseline in Fasting Fructosamine (Day 85).
    Description The change between the value of fasting fructosamine collected at day 85 or final visit and fasting fructosamine collected at baseline.
    Time Frame Baseline and Day 85.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 85. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 41 42 42 45 40 44
    Least Squares Mean (Standard Error) [mg/dL]
    7.7
    (6.03)
    0.2
    (5.91)
    -9.8
    (5.93)
    -16.4
    (5.71)
    -12.4
    (6.25)
    -4.8
    (5.82)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect will be evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.014
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -16.3
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.60
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.136
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.35
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.022
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -20.1
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.73
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -24.1
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.26
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.040
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -17.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.48
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in fasting fructosamine. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.378
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline fasting fructosamine as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.47
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    7. Secondary Outcome
    Title Change From Baseline in Total Cholesterol (Day 43).
    Description The change between the value of cholesterol collected at day 43 and cholesterol collected at baseline.
    Time Frame Baseline and Day 43

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 43. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 40 41 42 43 39 42
    Least Squares Mean (Standard Error) [mg/dL]
    -11.1
    (4.91)
    -9.7
    (4.85)
    -9.6
    (4.77)
    -9.8
    (4.71)
    -12.0
    (5.11)
    -4.7
    (4.80)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect will be evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.718
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.9
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.37
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.346
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.4
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.80
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.901
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.9
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.13
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.851
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.3
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.79
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.825
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.86
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.843
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.4
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.94
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    8. Secondary Outcome
    Title Change From Baseline in Total Cholesterol (Day 85).
    Description The change between the value of cholesterol collected at day 85 or final visit and cholesterol collected at baseline.
    Time Frame Baseline and Day 85.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 85. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 41 42 42 45 40 44
    Least Squares Mean (Standard Error) [mg/dL]
    -15.1
    (4.46)
    -9.0
    (4.41)
    -4.8
    (4.39)
    -8.7
    (4.24)
    -7.7
    (4.64)
    -0.4
    (4.31)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect will be evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.069
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.9
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.88
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 14.6
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.14
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.258
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.3
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.47
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.299
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.4
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.13
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.103
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 10.3
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.27
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in total cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.340
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline total cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.0
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.32
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    9. Secondary Outcome
    Title Change From Baseline in High-Density Lipoprotein Cholesterol (Day 43).
    Description The change between high-density lipoprotein cholesterol collected at day 43 and high-density lipoprotein cholesterol collected at baseline.
    Time Frame Baseline and Day 43.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 43. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 40 41 42 43 39 42
    Least Squares Mean (Standard Error) [mg/dL]
    -1.4
    (0.76)
    -0.6
    (0.75)
    -2.0
    (0.74)
    -2.4
    (0.73)
    -2.8
    (0.80)
    -1.1
    (0.74)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect will be evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.689
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.3
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.83
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.742
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.3
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.05
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.220
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.4
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.11
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.348
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.0
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.05
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.627
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.06
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.418
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.9
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.06
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    10. Secondary Outcome
    Title Change From Baseline in High-Density Lipoprotein Cholesterol (Day 85).
    Description The change between high-density lipoprotein cholesterol collected at day 85 or final visit and high-density lipoprotein cholesterol collected at baseline.
    Time Frame Baseline and Day 85.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 85. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 41 42 42 45 40 44
    Least Squares Mean (Standard Error) [mg/dL]
    -1.9
    (0.87)
    -0.7
    (0.86)
    -2.3
    (0.85)
    -2.5
    (0.83)
    -2.0
    (0.92)
    0.4
    (0.84)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect will be evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.617
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.95
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.052
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.3
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.20
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.906
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.2
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.28
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.628
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.6
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.19
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.749
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.4
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.22
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.340
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline HDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.2
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.22
    Estimation Comments Positive mean treatment difference indicates larger increase from baseline (more positive change from baseline) in the alogliptin arm compared to the placebo arm.
    11. Secondary Outcome
    Title Change From Baseline in Low-Density Lipoprotein Cholesterol (Day 43).
    Description The change between low-density lipoprotein cholesterol collected at day 43 and low-density lipoprotein cholesterol collected at baseline.
    Time Frame Baseline and Day 43.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 43. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 35 38 39 40 36 37
    Least Squares Mean (Standard Error) [mg/dL]
    -8.9
    (3.97)
    -3.8
    (3.79)
    -6.4
    (3.72)
    -1.5
    (3.69)
    -9.9
    (4.01)
    0.8
    (3.84)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect will be evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.269
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.8
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.31
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.076
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 9.7
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.46
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.867
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.9
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.66
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.169
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.4
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.40
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.645
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.45
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.351
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.2
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.51
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    12. Secondary Outcome
    Title Change From Baseline in Low-Density Lipoprotein Cholesterol (Day 85).
    Description The change between low-density lipoprotein cholesterol collected at day 85 or final visit and low-density lipoprotein cholesterol collected at baseline.
    Time Frame Baseline and Day 85.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 85. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 36 39 39 43 38 40
    Least Squares Mean (Standard Error) [mg/dL]
    -13.6
    (3.72)
    -2.6
    (3.55)
    -2.7
    (3.54)
    -0.6
    (3.38)
    -5.0
    (3.70)
    4.0
    (3.50)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect will be evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 12.3
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.03
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 17.6
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.06
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.103
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.6
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.26
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 13.0
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.98
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.034
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 11.0
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.14
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in LDL cholesterol. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.033
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline LDL cholesterol as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 11.1
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.16
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    13. Secondary Outcome
    Title Change From Baseline in Triglycerides (Day 43).
    Description The change between triglycerides collected at day 43 and triglycerides collected at baseline.
    Time Frame Baseline and Day 43.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 43. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 40 41 42 43 39 42
    Least Squares Mean (Standard Error) [mg/dL]
    -18.7
    (15.69)
    -28.0
    (15.43)
    -10.1
    (15.28)
    -27.7
    (15.10)
    -7.2
    (16.33)
    -31.5
    (15.48)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect will be evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.897
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.2
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 17.17
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.557
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.8
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 21.85
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.616
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 11.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 22.85
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.679
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -9.0
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 21.73
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.697
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 21.94
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.672
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -9.4
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 22.03
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    14. Secondary Outcome
    Title Change From Baseline in Triglycerides (Day 85).
    Description The change between triglycerides collected at day 85 or final visit and triglycerides collected at baseline.
    Time Frame Baseline and Day 85.

    Outcome Measure Data

    Analysis Population Description
    Randomized subjects who received at least 1 dose of study drug (Intent to Treat), and who had measurements at baseline and at Day 85. Missing data are imputed using last observation carried forward (LOCF).
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 41 42 42 45 40 44
    Least Squares Mean (Standard Error) [mg/dL]
    -13.9
    (14.98)
    -26.4
    (14.75)
    9.2
    (14.77)
    -32.9
    (14.27)
    -14.4
    (15.58)
    -24.9
    (14.59)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD, Alogliptin 50 mg QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect will be evaluated as a contrast of all doses of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.809
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.0
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 16.37
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 100 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.597
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.0
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 20.74
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 50 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.982
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 21.77
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.358
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -19.0
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 20.62
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 12.5 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.274
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 23.1
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 21.06
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo QD, Alogliptin 6.25 mg QD
    Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in triglycerides. The treatment effect was evaluated as a contrast of each dose of alogliptin versus placebo and was evaluated inferentially with a 2-sided t-test at the 0.05 significance level.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.554
    Comments No multiplicity adjustments.
    Method ANCOVA
    Comments Treatment and prior antidiabetic treatment as class effects and BMI, diabetes duration, and baseline triglycerides as covariates.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 21.06
    Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
    15. Secondary Outcome
    Title Mean Percent Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg/dL).
    Description The incidence of marked hyperglycemia occurring in participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during study. Overall mean obtained by weighting the hyperglycemia percent incidence values at each time point by number of days in between visits. Mean percent incidence of marked hyperglycemia at each time point is the percent of self-monitored blood glucose measurements greater than or equal to 200 mg per dL, calculated per participant and then averaged across population.
    Time Frame 85 Days.

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug (Intent to Treat), and who had at least 1 fasting plasma glucose measurement after baseline. Note: Mean percent incidence of marked hyperglycemia was only summarized by treatment group using descriptive statistics.
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    Measure Participants 41 42 42 45 43 44
    Mean (Standard Deviation) [percent incidence]
    54.0
    (34.95)
    34.7
    (33.43)
    25.8
    (26.92)
    28.1
    (25.94)
    30.4
    (30.32)
    30.6
    (29.92)

    Adverse Events

    Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind drug.
    Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
    Arm/Group Title Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks. Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks. Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.
    All Cause Mortality
    Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/41 (4.9%) 1/42 (2.4%) 0/44 (0%) 1/45 (2.2%) 0/43 (0%) 0/44 (0%)
    General disorders
    Noncardiac chest pain 0/41 (0%) 1/42 (2.4%) 0/44 (0%) 1/45 (2.2%) 0/43 (0%) 0/44 (0%)
    Injury, poisoning and procedural complications
    Intentional overdose 1/41 (2.4%) 0/42 (0%) 0/44 (0%) 0/45 (0%) 0/43 (0%) 0/44 (0%)
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 1/41 (2.4%) 0/42 (0%) 0/44 (0%) 0/45 (0%) 0/43 (0%) 0/44 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo QD Alogliptin 6.25 mg QD Alogliptin 12.5 mg QD Alogliptin 25 mg QD Alogliptin 50 mg QD Alogliptin 100 mg QD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/41 (34.1%) 12/42 (28.6%) 18/44 (40.9%) 19/45 (42.2%) 15/43 (34.9%) 22/44 (50%)
    Eye disorders
    Vision blurred 0/41 (0%) 1/42 (2.4%) 1/44 (2.3%) 2/45 (4.4%) 0/43 (0%) 0/44 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/41 (0%) 0/42 (0%) 2/44 (4.5%) 1/45 (2.2%) 0/43 (0%) 0/44 (0%)
    Abdominal pain upper 0/41 (0%) 2/42 (4.8%) 1/44 (2.3%) 3/45 (6.7%) 0/43 (0%) 0/44 (0%)
    Constipation 1/41 (2.4%) 0/42 (0%) 2/44 (4.5%) 0/45 (0%) 1/43 (2.3%) 0/44 (0%)
    Diarrhoea 3/41 (7.3%) 0/42 (0%) 1/44 (2.3%) 1/45 (2.2%) 3/43 (7%) 0/44 (0%)
    Nausea 0/41 (0%) 2/42 (4.8%) 1/44 (2.3%) 1/45 (2.2%) 2/43 (4.7%) 5/44 (11.4%)
    General disorders
    Fatigue 2/41 (4.9%) 0/42 (0%) 1/44 (2.3%) 0/45 (0%) 2/43 (4.7%) 3/44 (6.8%)
    Oedema peripheral 1/41 (2.4%) 1/42 (2.4%) 1/44 (2.3%) 0/45 (0%) 1/43 (2.3%) 2/44 (4.5%)
    Infections and infestations
    Fungal infection 2/41 (4.9%) 0/42 (0%) 0/44 (0%) 0/45 (0%) 0/43 (0%) 0/44 (0%)
    Gastroenteritis 1/41 (2.4%) 0/42 (0%) 0/44 (0%) 2/45 (4.4%) 0/43 (0%) 0/44 (0%)
    Gastroenteritis viral 0/41 (0%) 0/42 (0%) 2/44 (4.5%) 0/45 (0%) 0/43 (0%) 1/44 (2.3%)
    Nasopharyngitis 2/41 (4.9%) 0/42 (0%) 2/44 (4.5%) 2/45 (4.4%) 1/43 (2.3%) 1/44 (2.3%)
    Upper respiratory tract infection 0/41 (0%) 1/42 (2.4%) 0/44 (0%) 2/45 (4.4%) 1/43 (2.3%) 1/44 (2.3%)
    Urinary tract infection 4/41 (9.8%) 3/42 (7.1%) 1/44 (2.3%) 3/45 (6.7%) 3/43 (7%) 4/44 (9.1%)
    Investigations
    Weight decreased 0/41 (0%) 0/42 (0%) 1/44 (2.3%) 2/45 (4.4%) 0/43 (0%) 1/44 (2.3%)
    Metabolism and nutrition disorders
    Hyperglycaemia 0/41 (0%) 0/42 (0%) 2/44 (4.5%) 0/45 (0%) 0/43 (0%) 0/44 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/41 (0%) 1/42 (2.4%) 2/44 (4.5%) 0/45 (0%) 0/43 (0%) 1/44 (2.3%)
    Back pain 1/41 (2.4%) 1/42 (2.4%) 0/44 (0%) 1/45 (2.2%) 2/43 (4.7%) 1/44 (2.3%)
    Myalgia 0/41 (0%) 1/42 (2.4%) 1/44 (2.3%) 0/45 (0%) 0/43 (0%) 3/44 (6.8%)
    Neck pain 0/41 (0%) 0/42 (0%) 2/44 (4.5%) 0/45 (0%) 0/43 (0%) 0/44 (0%)
    Pain in extremity 0/41 (0%) 1/42 (2.4%) 1/44 (2.3%) 3/45 (6.7%) 0/43 (0%) 2/44 (4.5%)
    Nervous system disorders
    Dizziness 0/41 (0%) 2/42 (4.8%) 0/44 (0%) 3/45 (6.7%) 1/43 (2.3%) 1/44 (2.3%)
    Headache 3/41 (7.3%) 2/42 (4.8%) 0/44 (0%) 4/45 (8.9%) 3/43 (7%) 4/44 (9.1%)
    Paraesthesia 0/41 (0%) 0/42 (0%) 2/44 (4.5%) 0/45 (0%) 0/43 (0%) 0/44 (0%)
    Somnolence 0/41 (0%) 0/42 (0%) 0/44 (0%) 2/45 (4.4%) 0/43 (0%) 0/44 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/41 (2.4%) 0/42 (0%) 1/44 (2.3%) 0/45 (0%) 0/43 (0%) 2/44 (4.5%)
    Pharyngolaryngeal pain 0/41 (0%) 0/42 (0%) 0/44 (0%) 2/45 (4.4%) 0/43 (0%) 2/44 (4.5%)
    Skin and subcutaneous tissue disorders
    Rash 1/41 (2.4%) 0/42 (0%) 4/44 (9.1%) 0/45 (0%) 1/43 (2.3%) 1/44 (2.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.

    Results Point of Contact

    Name/Title Sr. VP, Clinical Science
    Organization Takeda Global Research and Development Center, Inc.
    Phone 800-778-2860
    Email clinicaltrialregistry@tpna.com
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT00755846
    Other Study ID Numbers:
    • SYR-322-003
    • U1111-1113-8352
    First Posted:
    Sep 19, 2008
    Last Update Posted:
    Feb 3, 2012
    Last Verified:
    Feb 1, 2012