Efficacy of Alogliptin With Pioglitazone (Actos®) in Subjects With Type 2 Diabetes Mellitus

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT00395512
Collaborator
(none)
655
161
4
15
4.1
0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the combination of alogliptin, once daily (QD), and pioglitazone in patients with type 2 diabetes mellitus who are inadequately controlled with diet and exercise alone.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% is type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected, placing an ever-increasing burden on families and the health care system.

Current pharmacologic interventions for type 2 diabetes mellitus include a diverse range of antidiabetic medications with different mechanisms of action including insulin and insulin analogues, sulfonylureas, metformin, meglitinides, thiazolidinediones, inhibitors of alpha- glucosidase, analogs of glucagon-like peptide-1, and synthetic analogues of human amylin. Despite the variety of medications, many have clinically important or potentially life-threatening side effects, restricted use in many subpopulations, concerns with long-term tolerability, and challenges related to compliance due to side effects and route of administration. All of these reasons contribute to the difficulties patients have reaching the target glycosylated hemoglobin level less than 7%.

SYR-322 (alogliptin) is a selective, orally available inhibitor of the dipeptidyl peptidase-4 enzyme. Dipeptidyl peptidase-4 enzyme 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. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus.

Pioglitazone (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan) that is approved for the treatment of type 2 diabetes mellitus. Pioglitazone is a selective peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in the periphery and liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output.

As the rate of newly diagnosed cases of type 2 diabetes mellitus continues to grow, so does the need for products that will provide better glycemic control and improved safety and tolerability. Alogliptin and pioglitazone have complementary actions. Alogliptin inhibits the degradation of glucagon-like peptide-1 by inhibiting the enzyme dipeptidyl peptidase IV, thus augmenting glucose-dependent insulin secretion while pioglitazone is a peripheral and hepatic insulin sensitizer. Given the complementary mechanisms of action of alogliptin (stimulates insulin secretion) and pioglitazone (enhances insulin sensitivity), the addition of combination therapy in treatment naïve type 2 diabetes patients may potentially allow the patients to reach and maintain their glycosylated hemoglobin goal more effectively.

The aim of this study is to evaluate the effectiveness of the combination of alogliptin with pioglitazone in patients who are inadequately controlled on diet and exercise alone. Study participation is anticipated to be approximately 8.5 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
655 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Double-Blind Study to Determine the Efficacy and Safety of SYR-322 Plus Pioglitazone HCl (Actos®), SYR-322 Alone or Pioglitazone HCl Alone in Subjects With Type 2 Diabetes
Study Start Date :
Nov 1, 2006
Actual Primary Completion Date :
Feb 1, 2008
Actual Study Completion Date :
Feb 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Alogliptin 25 mg QD

Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.

Drug: Alogliptin
Alogliptin tablets.
Other Names:
  • SYR-322
  • Drug: Placebo
    Matching placebo tablets.

    Active Comparator: Pioglitazone 30 mg QD

    Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.

    Drug: Pioglitazone
    Pioglitazone tablets.
    Other Names:
  • Actos
  • AD4833
  • Drug: Placebo
    Matching placebo tablets.

    Experimental: Alogliptin 25 mg QD+ Pioglitazone 30 mg QD

    Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.

    Drug: Alogliptin
    Alogliptin tablets.
    Other Names:
  • SYR-322
  • Drug: Pioglitazone
    Pioglitazone tablets.
    Other Names:
  • Actos
  • AD4833
  • Active Comparator: Alogliptin 12.5 mg QD + Pioglitazone 30 mg QD

    Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.

    Drug: Alogliptin
    Alogliptin tablets.
    Other Names:
  • SYR-322
  • Drug: Pioglitazone
    Pioglitazone tablets.
    Other Names:
  • Actos
  • AD4833
  • Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) [Baseline and Week 26]

      The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).

    Secondary Outcome Measures

    1. Change From Baseline in HbA1c Over Time [Baseline and Weeks 4, 8, 12, 16 and 20.]

      The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at 4 week intervals during the study. Least Squares Means were from an Analysis of Covariance (ANCOVA) model with treatment and geographic region as class variables and baseline HbA1c as a covariate.

    2. Change From Baseline in Fasting Plasma Glucose Over Time [Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.]

      The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline plasma glucose as a covariate.

    3. Percentage of Participants With Marked Hyperglycemia [Weeks 1, 2, 4, 8, 12, 16, 20 and 26.]

      Marked Hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL. Study week windows are defined to place hyperglycemia into visit categories.

    4. Percentage of Participants Meeting Rescue Criteria [Weeks 4, 8, 12, 16, 20 and 26.]

      Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days after the first sample and analyzed by the central laboratory: After more than 4 weeks of treatment but prior to the Week 8 Visit: a single fasting plasma glucose ≥310 mg/dL (≥17.5 mmol/L); From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥275 mg/dL (≥15.27 mmol/L); From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with the Baseline HbA1c.

    5. Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5% [Week 26]

      Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤6.5%.

    6. Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0% [Week 26]

      Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤ 7%.

    7. Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.5% [Week 26]

      Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤ 7.5%.

    8. Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 0.5% [Baseline and Week 26]

      Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 0.5%.

    9. Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.0% [Baseline and Week 26]

      Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 1%.

    10. Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.5%. [Baseline and Week 26]

      Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 1.5%.

    11. Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 2.0% [Baseline and Week 26]

      Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 2.0%.

    12. Change From Baseline in Fasting Proinsulin [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]

      Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline proinsulin as a covariate.

    13. Change From Baseline in Insulin [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]

      The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline insulin as a covariate.

    14. Change From Baseline in Proinsulin/Insulin Ratio [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]

      The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20 and 26 relative to the Baseline value. Least squares means were from an ANCOVA model with treatment and geographic region as class variables and Baseline proinsulin/insulin ratio as a covariate.

    15. Change From Baseline in C-peptide Levels [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]

      C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline C-peptide as a covariate.

    16. Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance [Baseline and Weeks 12 and 26.]

      The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5 A higher number indicates a greater degree of insulin resistance. The change from Baseline in HOMA IR was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HOMA IR as a covariate.

    17. Change From Baseline in Homeostatic Model Assessment Beta Cell Function [Baseline and Weeks 12 and 26.]

      The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5 The change from Baseline in the homeostasis model assessment of beta cell function was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HOMA beta cell function as a covariate.

    18. Change From Baseline in Body Weight [Baseline and Weeks 8, 12, 20 and 26.]

      Change from Baseline in body weight was assessed at Weeks 8, 12, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and Baseline weight as a covariate.

    19. Change From Baseline in Total Cholesterol Level [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]

      Change from Baseline in total cholesterol level was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline total cholesterol as a covariate.

    20. Change From Baseline in Low-Density Lipoprotein Cholesterol [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]

      Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline LDL cholesterol as a covariate.

    21. Change From Baseline in High-Density Lipoprotein Cholesterol [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]

      Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HDL cholesterol as a covariate.

    22. Change From Baseline in Triglyceride Levels [Baseline and Weeks 4, 8, 12, 16, 20 and 26.]

      Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline triglycerides as a covariate.

    23. Change From Baseline in Free Fatty Acids [Baseline and Weeks 12 and 26.]

      Change from Baseline in free fatty acids (FFA) was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline free fatty acid as a covariate.

    24. Change From Baseline in Plasminogen Activator Inhibitor-1 [Baseline and Weeks 12 and 26.]

      Change from Baseline in plasminogen activator inhibitor-1 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline plasminogen activator inhibitor-1 as a covariate.

    25. Change From Baseline in High-sensitivity C-Reactive Protein [Baseline and Weeks 12 and 26.]

      Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline hsCRP as a covariate.

    26. Change From Baseline in Adiponectin [Baseline and Weeks 12 and 26.]

      Change from Baseline in adiponectin was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline adiponectin as a covariate.

    27. Change From Baseline in Apolipoprotein A1 [Baseline and Weeks 12 and 26.]

      Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and Baseline apolipoprotein A1 as a covariate.

    28. Change From Baseline in Apolipoprotein A2 [Baseline and Weeks 12 and 26.]

      Change from Baseline in apolipoprotein A2 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein A2 as a covariate.

    29. Change From Baseline in Apolipoprotein B [Baseline and Weeks 12 and 26.]

      Change from Baseline in apolipoprotein B was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein B as a covariate.

    30. Change From Baseline in Apolipoprotein C-III [Baseline and Weeks 12 and 26.]

      Change from Baseline in apolipoprotein C-III was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein C-III as a covariate.

    31. Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides [Baseline and Weeks 12 and 26.]

      Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline NMR total triglycerides as a covariate.

    32. Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles [Baseline and Weeks 12 and 26.]

      The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL/chylomicron particles as a covariate.

    33. Change From Baseline in VLDL / Chylomicron Triglycerides [Baseline and Weeks 12 and 26.]

      The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL/chylomicron triglycerides as a covariate.

    34. Change From Baseline in VLDL Particles [Baseline and Weeks 12 and 26.]

      The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL particles as a covariate.

    35. Change From Baseline in Mean VLDL Particle Size [Baseline and Weeks 12 and 26.]

      Change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean VLDL particle size as a covariate.

    36. Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles [Baseline and Weeks 12 and 26.]

      The change from Baseline in levels of IDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline IDL particles as a covariate.

    37. Change From Baseline in Low Density Lipoprotein (LDL) Particles [Baseline and Weeks 12 and 26.]

      The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline LDL particles as a covariate.

    38. Change From Baseline in Mean LDL Particle Size [Baseline and Weeks 12 and 26.]

      Change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean LDL particle size as a covariate.

    39. Change From Baseline in High Density Lipoprotein (HDL) Particles [Baseline and Weeks 12 and 26.]

      The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HDL particles as a covariate.

    40. Change From Baseline in Mean HDL Particle Size [Baseline and Weeks 12 and 26.]

      Change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean HDL particle size as a covariate.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • Historical diagnosis of type 2 diabetes.

    • Failed treatment with diet and exercise for at least 2 months prior to Screening.

    • Is experiencing inadequate glycemic control as defined as glycosylated hemoglobin concentration between 7.5-11%, inclusive.

    • Has received any antidiabetic therapy for less than 7 days within 3 months prior to Screening.

    • Has a body mass index greater than or equal to 23 kg/m2 and less than or equal to45 kg/m2.

    • Fasting C-peptide greater than or equal to 0.8 ng per mL.

    • Regular use of other, non-excluded medications is allowed if participant is on a stable dose for at least 4 weeks prior to Screening.

    • Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

    • Must be willing and able to monitor their blood concentrations with a home glucose monitor.

    Exclusion Criteria

    • Systolic blood pressure greater than or equal to 160 mmHg and diastolic blood pressure greater than or equal to 100 mmHg.

    • Hemoglobin less than or equal to 12 g per dL for males and less than or equal to 10 g per dL for females.

    • Alanine aminotransferase greater than or equal to 2.5times the upper limit of normal.

    • Serum creatinine greater than 2.0 mg per dL.

    • Thyroid stimulating hormone level greater than the upper limit of normal range.

    • Major illness or debility that in the investigator's opinion prohibits the subject from completing the study.

    • Urine albumin to creatinine ratio of greater than 1000 ug per mg at Screening. If elevated, the subject may be rescreened within 1 week.

    • History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening

    • History of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.

    • History of gastroparesis.

    • Has New York Heart Association Class I to IV heart failure regardless of therapy.

    • History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.

    • History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin.

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

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

    • History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors.

    • Any alteration in angiotensin-II receptor inhibitors within 2 months prior to Randomization, if applicable.

    • History of alcohol (defined as regular or daily consumption of more than 4 alcoholic drinks per day) or substance abuse (defined as illicit drug use) within 2 years prior to Screening.

    • Received any investigational drug within 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within 3 months prior to Screening.

    • Previously participated in an investigational study of SYR-322.

    • Glycosylated hemoglobin concentration between 7.5-11%, inclusive, and a fasting plasma glucose less than 310 mg per dL.

    • At least 75% compliant with the single-blind placebo regimen during the run-in/stabilization period.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Columbiana Alabama United States
    2 Hueytown Alabama United States
    3 Huntsville Alabama United States
    4 Northport Alabama United States
    5 Tucson Arizona United States
    6 Jonesboro Arkansas United States
    7 Little Rock Arkansas United States
    8 Searcy Arkansas United States
    9 Foothill Ranch California United States
    10 Irvine California United States
    11 Northridge California United States
    12 San Diego California United States
    13 San Mateo California United States
    14 Santa Monica California United States
    15 Jacksonville Florida United States
    16 Melbourne Florida United States
    17 Miami Florida United States
    18 Port Charlotte Florida United States
    19 Sebastian Florida United States
    20 South Miami Florida United States
    21 Winter Haven Florida United States
    22 Augusta Georgia United States
    23 Barnesville Georgia United States
    24 Columbus Georgia United States
    25 Savannah Georgia United States
    26 Chicago Illinois United States
    27 Libertyville Illinois United States
    28 South Bend Indiana United States
    29 Bossier City Louisiana United States
    30 Elkton Maryland United States
    31 Prince Frederick Maryland United States
    32 Towson Maryland United States
    33 North Dartmouth Massachusetts United States
    34 Bay City Michigan United States
    35 Benzonia Michigan United States
    36 Portage Michigan United States
    37 St Clair Shores Michigan United States
    38 Picayune Mississippi United States
    39 St Louis Missouri United States
    40 Billings Montana United States
    41 Las Vegas Nevada United States
    42 Elizabeth New Jersey United States
    43 Hamilton New Jersey United States
    44 Cicero New York United States
    45 Charlotte North Carolina United States
    46 Mooresville North Carolina United States
    47 Northeast North Dakota United States
    48 Franklin Ohio United States
    49 Ashland Oregon United States
    50 Altoona Pennsylvania United States
    51 Fleetwood Pennsylvania United States
    52 Harleysville Pennsylvania United States
    53 Havertown Pennsylvania United States
    54 Norristown Pennsylvania United States
    55 Northern Cambria Pennsylvania United States
    56 Penndel Pennsylvania United States
    57 Philadelphia Pennsylvania United States
    58 Charleston South Carolina United States
    59 Florence South Carolina United States
    60 Orangeburg South Carolina United States
    61 Taylors South Carolina United States
    62 Williamston South Carolina United States
    63 Morristown Tennessee United States
    64 Arlington Texas United States
    65 Colleyville Texas United States
    66 Conroe Texas United States
    67 Corpus Christi Texas United States
    68 Dallas Texas United States
    69 Euless Texas United States
    70 Fort Worth Texas United States
    71 Garland Texas United States
    72 Houston Texas United States
    73 Katy Texas United States
    74 San Antonio Texas United States
    75 Seguin Texas United States
    76 Sugarland Texas United States
    77 Tomball Texas United States
    78 Ogden Utah United States
    79 Arlington Virginia United States
    80 Norfolk Virginia United States
    81 Richmond Virginia United States
    82 Lewisburg West Virginia United States
    83 Milwaukee Wisconsin United States
    84 Cap. Fed. Buenos Aires Argentina
    85 Chacabuco Buenos Aires Argentina
    86 La Plata Buenos Aires Argentina
    87 Mar del Plata Buenos Aires Argentina
    88 Morón Buenos Aires Argentina
    89 Córdoba Argentina
    90 Kingswood New South Wales Australia
    91 Fitzroy Victoria Australia
    92 Frankston Victoria Australia
    93 Fortaleza CE Brazil
    94 Goiás GO Brazil
    95 Belém PA Brazil
    96 Curitiba PR Brazil
    97 Maringá RP Brazil
    98 Marília SP Brazil
    99 Mogi das Cruzes SP Brazil
    100 Pleven Bulgaria
    101 Santiago Chile
    102 Slavonski Brod Croatia
    103 Pärnu Estonia
    104 Guatemala Guatemala
    105 Budapest Hungary
    106 Eger Hungary
    107 Gyula Hungary
    108 Mako Hungary
    109 Nyiregyhaza Hungary
    110 Pecs Hungary
    111 Hyderabad Andhra Pradesh India
    112 Bangalore Karnataka India
    113 Aurangabad Maharashtra India
    114 Mumbai Maharashtra India
    115 Nagpur Maharashtra India
    116 Chennai Tamil Nadu India
    117 Hadera Israel
    118 Haifa Israel
    119 Holon Israel
    120 Jaffa Tel Aviv Israel
    121 Jerusalem Israel
    122 Nahariya Israel
    123 Riga Latvia
    124 Kaunas Lithuania
    125 Kedainiai Lithuania
    126 Aguascalientes Mexico
    127 Mexico City Mexico
    128 Monterrey Mexico
    129 Christchurch New Zealand
    130 Hamilton New Zealand
    131 Bialystok Poland
    132 Bytom Poland
    133 Gdansk Poland
    134 Gniewkowo Poland
    135 Kamieniec Zabkowicki Poland
    136 Krakow Poland
    137 Leczyca Poland
    138 Brasov Romania
    139 Bucharest Romania
    140 Galati Romania
    141 Ekaterinburg Russian Federation
    142 Kazan Russian Federation
    143 Moscow Russian Federation
    144 Belgrade Serbia
    145 Kragujevac Serbia
    146 Nis Serbia
    147 Interna klinika II Nitra Slovakia
    148 Banska Bysterica Slovakia
    149 Lucenec Slovakia
    150 Riverside Slovakia
    151 Sahy Slovakia
    152 Port Elizabeth Eastern Cape South Africa
    153 Johannesburg Gauteng South Africa
    154 Durban Kwa-Zulu Natal South Africa
    155 East Lynne Pretoria South Africa
    156 Bellville Western Province South Africa
    157 Cape Town Western Province South Africa
    158 Dnipropetrovsk Ukraine
    159 Kharkiv Ukraine
    160 Lviv Ukraine
    161 Odesa Ukraine

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Director: VP, Biological Sciences, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT00395512
    Other Study ID Numbers:
    • 01-06-TL-322OPI-002
    • 2006-005492-17
    • U1111-1113-8616
    First Posted:
    Nov 3, 2006
    Last Update Posted:
    Mar 27, 2013
    Last Verified:
    Feb 1, 2013

    Study Results

    Participant Flow

    Recruitment Details Participants took part in the study at 268 investigative sites in 23 countries from 02 November 2006 to 13 February 2008.
    Pre-assignment Detail Participants with a diagnosis of type 2 diabetes who were inadequately controlled with diet and exercise were randomized to 1 of 4 treatment groups in a 1:1:1:1 ratio as follows: Alogliptin alone, pioglitazone alone, alogliptin 25 mg + pioglitazone 30 mg and alogliptin 12.5 mg + pioglitazone 30 mg.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Period Title: Overall Study
    STARTED 164 163 164 164
    Safety Set 164 163 164 163
    COMPLETED 126 126 136 126
    NOT COMPLETED 38 37 28 38

    Baseline Characteristics

    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg Total
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Total of all reporting groups
    Overall Participants 164 163 164 164 655
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    52.6
    (10.38)
    51.5
    (10.72)
    52.8
    (11.01)
    53.5
    (11.37)
    52.6
    (10.88)
    Age, Customized (participants) [Number]
    < 65 years
    144
    87.8%
    143
    87.7%
    140
    85.4%
    130
    79.3%
    557
    85%
    ≥ 65 years
    20
    12.2%
    20
    12.3%
    24
    14.6%
    34
    20.7%
    98
    15%
    Sex: Female, Male (Count of Participants)
    Female
    88
    53.7%
    73
    44.8%
    91
    55.5%
    83
    50.6%
    335
    51.1%
    Male
    76
    46.3%
    90
    55.2%
    73
    44.5%
    81
    49.4%
    320
    48.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    63
    38.4%
    65
    39.9%
    58
    35.4%
    62
    37.8%
    248
    37.9%
    Not Hispanic or Latino
    101
    61.6%
    98
    60.1%
    106
    64.6%
    102
    62.2%
    407
    62.1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    0.6%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    Asian
    14
    8.5%
    15
    9.2%
    12
    7.3%
    16
    9.8%
    57
    8.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    1
    0.6%
    1
    0.2%
    Black or African American
    8
    4.9%
    9
    5.5%
    12
    7.3%
    9
    5.5%
    38
    5.8%
    White
    135
    82.3%
    130
    79.8%
    129
    78.7%
    132
    80.5%
    526
    80.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    6
    3.7%
    9
    5.5%
    11
    6.7%
    6
    3.7%
    32
    4.9%
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    86.72
    (19.033)
    85.53
    (16.254)
    85.39
    (20.374)
    84.38
    (20.378)
    85.50
    (19.062)
    Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    31.61
    (5.587)
    30.87
    (4.938)
    31.32
    (5.354)
    30.71
    (5.621)
    31.13
    (5.382)
    Duration of diabetes (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    3.23
    (3.559)
    3.20
    (3.739)
    3.05
    (3.328)
    3.36
    (4.166)
    3.21
    (3.704)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c)
    Description The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
    Time Frame Baseline and Week 26

    Outcome Measure Data

    Analysis Population Description
    The Full analysis Set (all randomized patients who took at least 1 dose of double-blind study drug) where a Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 160 153 158 158
    Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]
    -0.96
    (0.081)
    -1.15
    (0.083)
    -1.71
    (0.081)
    -1.56
    (0.081)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pioglitazone 30 mg, Alogliptin 25 mg + Pioglitazone 30 mg
    Comments The primary efficacy variable was defined as change from Baseline in HbA1c level at Week 26. The null hypothesis was that the average change from Baseline in HbA1c at Week 26 for the A25 + P30 group would be equal to the average changes for the P30 alone and A25 alone groups; further, under the null hypothesis, the average change from Baseline in HbA1c at Week 26 for the A12.5 + P30 group was equal to the average change for the P30 alone group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments ANCOVA model with treatment and geographic region as class variables and baseline HbA1c as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.56
    Confidence Interval (2-Sided) 95%
    -0.78 to -0.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg, Alogliptin 25 mg + Pioglitazone 30 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments ANCOVA model with treatment and geographic region as class variables and baseline HbA1c as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.75
    Confidence Interval (2-Sided) 95%
    -0.98 to -0.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pioglitazone 30 mg, Alogliptin 12.5 mg + Pioglitazone 30 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments ANCOVA model with treatment and geographic region as class variables and baseline HbA1c as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -0.63 to -0.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in HbA1c Over Time
    Description The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at 4 week intervals during the study. Least Squares Means were from an Analysis of Covariance (ANCOVA) model with treatment and geographic region as class variables and baseline HbA1c as a covariate.
    Time Frame Baseline and Weeks 4, 8, 12, 16 and 20.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 4 (n=145, 146, 144, 150)
    -0.55
    (0.043)
    -0.30
    (0.043)
    -0.62
    (0.043)
    -0.51
    (0.043)
    Week 8 (n=160, 153, 158, 158)
    -0.84
    (0.058)
    -0.72
    (0.060)
    -1.19
    (0.059)
    -1.03
    (0.059)
    Week 12 (n=160, 153, 158, 158)
    -0.98
    (0.070)
    -1.04
    (0.071)
    -1.57
    (0.070)
    -1.34
    (0.070)
    Week 16 (n=160, 153, 158, 158)
    -1.01
    (0.080)
    -1.17
    (0.082)
    -1.67
    (0.081)
    -1.43
    (0.081)
    Week 20 (n=160, 153, 158, 158)
    -1.00
    (0.077)
    -1.20
    (0.079)
    -1.72
    (0.078)
    -1.54
    (0.078)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pioglitazone 30 mg, Alogliptin 12.5 mg + Pioglitazone 30 mg
    Comments Comparison of change from Baseline at Week 20 between Pioglitazone 30 mg and Alogliptin 12.5 mg + Pioglitazone 30 mg.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment and geographic region as class variables and baseline HbA1c as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.33
    Confidence Interval (2-Sided) 95%
    -0.55 to -0.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pioglitazone 30 mg, Alogliptin 25 mg + Pioglitazone 30 mg
    Comments Comparison of change from Baseline at Week 20 between Pioglitazone 30 mg and Alogliptin 25 mg + Pioglitazone 30 mg.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment and geographic region as class variables and baseline HbA1c as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.52
    Confidence Interval (2-Sided) 95%
    -0.74 to -0.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg, Alogliptin 25 mg + Pioglitazone 30 mg
    Comments Comparison of change from Baseline at Week 20 between Alogliptin 25 mg and Alogliptin 25 mg + Pioglitazone 30 mg.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment and geographic region as class variables and baseline HbA1c as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.73
    Confidence Interval (2-Sided) 95%
    -0.94 to -0.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline in Fasting Plasma Glucose Over Time
    Description The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline plasma glucose as a covariate.
    Time Frame Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 1 (n=148, 146, 152, 151)
    -14.6
    (2.93)
    -7.3
    (2.95)
    -26.6
    (2.90)
    -23.3
    (2.91)
    Week 2 (n=161, 156, 162, 159)
    -16.7
    (2.87)
    -14.2
    (2.92)
    -33.5
    (2.87)
    -30.9
    (2.90)
    Week 4 (n=162, 157, 162, 161)
    -26.7
    (2.72)
    -31.9
    (2.76)
    -41.4
    (2.72)
    -39.7
    (2.73)
    Week 8 (n=162, 157, 162, 162)
    -29.0
    (2.80)
    -38.0
    (2.84)
    -50.4
    (2.80)
    -48.4
    (2.81)
    Week 12 (n=162, 157, 162, 162)
    -29.5
    (3.01)
    -42.4
    (3.05)
    -51.9
    (3.01)
    -49.3
    (3.01)
    Week 16 (n=162, 157, 162, 162)
    -26.9
    (3.11)
    -40.6
    (3.16)
    -52.7
    (3.12)
    -46.6
    (3.12)
    Week 20 (n=162, 157, 162, 162)
    -28.3
    (3.06)
    -42.0
    (3.11)
    -54.0
    (3.07)
    -47.5
    (3.07)
    Week 26 (n=162, 157, 162, 162)
    -25.8
    (3.26)
    -37.3
    (3.31)
    -50.2
    (3.27)
    -48.5
    (3.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pioglitazone 30 mg, Alogliptin 12.5 mg + Pioglitazone 30 mg
    Comments Comparison of change from Baseline in fasting plasma glucose at Week 26 between Pioglitazone 30 mg and Alogliptin 12.5 mg + Pioglitazone 30 mg.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments
    Method ANCOVA
    Comments P-value is from an ANCOVA model with treatment and geographic region as class variables and Baseline fasting plasma glucose as covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -11.2
    Confidence Interval (2-Sided) 95%
    -20.3 to -2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pioglitazone 30 mg, Alogliptin 25 mg + Pioglitazone 30 mg
    Comments Comparison of change from Baseline in fasting plasma glucose at Week 26 between Pioglitazone 30 mg and Alogliptin 25 mg + Pioglitazone 30 mg.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments
    Method ANCOVA
    Comments P-value is from an ANCOVA model with treatment and geographic region as class variables and Baseline fasting plasma glucose as covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -12.9
    Confidence Interval (2-Sided) 95%
    -22.0 to -3.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg, Alogliptin 25 mg + Pioglitazone 30 mg
    Comments Comparison of change from Baseline in fasting plasma glucose at Week 26 between Alogliptin 25 mg and Alogliptin 25 mg + Pioglitazone 30 mg.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments P-value is from an ANCOVA model with treatment and geographic region as class variables and Baseline fasting plasma glucose as covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -24.5
    Confidence Interval (2-Sided) 95%
    -33.5 to -15.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants With Marked Hyperglycemia
    Description Marked Hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL. Study week windows are defined to place hyperglycemia into visit categories.
    Time Frame Weeks 1, 2, 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    Full analysis set including patients with at least one non-missing fasting plasma glucose result in the specified interval in each treatment group.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 1 to < Week 4 (n=162, 157, 162, 161)
    31.5
    19.2%
    31.8
    19.5%
    18.5
    11.3%
    28.6
    17.4%
    Week 4 to < Week 8 (n=153, 147, 148, 147)
    19.0
    11.6%
    15.0
    9.2%
    10.8
    6.6%
    14.3
    8.7%
    Week 8 to < Week 12 (n=151, 146, 152, 146)
    15.2
    9.3%
    11.6
    7.1%
    7.2
    4.4%
    8.2
    5%
    Week 12 to < Week 16 (n=153, 141, 148, 139)
    16.3
    9.9%
    9.2
    5.6%
    8.1
    4.9%
    7.9
    4.8%
    Week 16 to < Week 20 (n=142, 135, 144, 131)
    16.2
    9.9%
    14.8
    9.1%
    2.8
    1.7%
    6.9
    4.2%
    Week 20 to Week 26 (n=130, 132, 143, 128)
    17.7
    10.8%
    11.4
    7%
    10.5
    6.4%
    6.3
    3.8%
    Overall (n=162, 157, 162, 162)
    44.4
    27.1%
    38.2
    23.4%
    25.3
    15.4%
    30.9
    18.8%
    5. Secondary Outcome
    Title Percentage of Participants Meeting Rescue Criteria
    Description Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days after the first sample and analyzed by the central laboratory: After more than 4 weeks of treatment but prior to the Week 8 Visit: a single fasting plasma glucose ≥310 mg/dL (≥17.5 mmol/L); From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥275 mg/dL (≥15.27 mmol/L); From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with the Baseline HbA1c.
    Time Frame Weeks 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    Full analysis set including patients with visits during or after the specified interval in each treatment group.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 4 to < Week 8 (n=160, 156, 161, 160)
    0
    0%
    0
    0%
    0
    0%
    0.6
    0.4%
    Week 8 to < Week 12 (n=158, 151, 157, 153)
    1.3
    0.8%
    0
    0%
    0
    0%
    0
    0%
    Week 12 to < Week 16 (n=156, 145, 153, 144)
    2.6
    1.6%
    3.4
    2.1%
    1.3
    0.8%
    2.1
    1.3%
    Week 16 to < Week 20 (n=150, 138, 149, 134)
    7.3
    4.5%
    2.2
    1.3%
    0
    0%
    1.5
    0.9%
    Week 20 to Week 26 (n=132, 133, 146, 130)
    0.8
    0.5%
    1.5
    0.9%
    1.4
    0.9%
    0
    0%
    Overall (n=160, 156, 161, 160)
    11.3
    6.9%
    6.4
    3.9%
    2.5
    1.5%
    3.8
    2.3%
    6. Secondary Outcome
    Title Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%
    Description Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤6.5%.
    Time Frame Week 26

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Number [percentage of participants]
    11.6
    7.1%
    16.6
    10.2%
    27.4
    16.7%
    26.4
    16.1%
    7. Secondary Outcome
    Title Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%
    Description Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤ 7%.
    Time Frame Week 26

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Number [percentage of participants]
    24.4
    14.9%
    33.7
    20.7%
    62.8
    38.3%
    53.4
    32.6%
    8. Secondary Outcome
    Title Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.5%
    Description Clinical response at Week 26 was assessed by the percentage of participants with HbA1c ≤ 7.5%.
    Time Frame Week 26

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Number [percentage of participants]
    44.5
    27.1%
    55.8
    34.2%
    72.0
    43.9%
    72.4
    44.1%
    9. Secondary Outcome
    Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 0.5%
    Description Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 0.5%.
    Time Frame Baseline and Week 26

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Number [percentage of participants]
    66.5
    40.5%
    70.6
    43.3%
    89.6
    54.6%
    85.3
    52%
    10. Secondary Outcome
    Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.0%
    Description Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 1%.
    Time Frame Baseline and Week 26

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Number [percentage of participants]
    43.3
    26.4%
    54.6
    33.5%
    75.6
    46.1%
    68.1
    41.5%
    11. Secondary Outcome
    Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.5%.
    Description Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 1.5%.
    Time Frame Baseline and Week 26

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Number [percentage of participants]
    29.3
    17.9%
    33.1
    20.3%
    57.3
    34.9%
    50.9
    31%
    12. Secondary Outcome
    Title Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 2.0%
    Description Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of ≥ 2.0%.
    Time Frame Baseline and Week 26

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Participants who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Number [percentage of participants]
    17.7
    10.8%
    19.6
    12%
    34.1
    20.8%
    33.1
    20.2%
    13. Secondary Outcome
    Title Change From Baseline in Fasting Proinsulin
    Description Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline proinsulin as a covariate.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 4 (n=136, 134, 135, 145)
    -4.9
    (1.74)
    -12.1
    (1.75)
    -16.0
    (1.74)
    -12.3
    (1.68)
    Week 8 (n=150, 143, 146, 155)
    -3.7
    (1.57)
    -14.9
    (1.60)
    -18.2
    (1.59)
    -17.7
    (1.54)
    Week 12 (n=150, 143, 147, 155)
    -5.9
    (1.48)
    -16.0
    (1.52)
    -18.6
    (1.50)
    -16.7
    (1.46)
    Week 16 (n=150, 143, 147, 155)
    -3.4
    (1.88)
    -16.3
    (1.93)
    -16.0
    (1.90)
    -13.1
    (1.85)
    Week 20 (n=150, 143, 147, 155)
    -8.1
    (1.75)
    -16.1
    (1.79)
    -19.8
    (1.76)
    -15.5
    (1.72)
    Week 26 (n=150, 143, 147, 155)
    -4.8
    (1.64)
    -13.2
    (1.68)
    -18.3
    (1.66)
    -15.1
    (1.61)
    14. Secondary Outcome
    Title Change From Baseline in Insulin
    Description The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as class variables and baseline insulin as a covariate.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 4 (n=135, 133, 133, 145)
    0.43
    (0.684)
    -4.74
    (0.689)
    -4.67
    (0.687)
    -4.27
    (0.659)
    Week 8 (n=150, 142, 147, 155)
    0.93
    (0.811)
    -4.41
    (0.834)
    -4.75
    (0.818)
    -4.86
    (0.797)
    Week 12 (n=150, 142, 148, 155)
    0.29
    (0.883)
    -4.08
    (0.907)
    -2.98
    (0.887)
    -4.65
    (0.867)
    Week 16 (n=150, 142, 148, 155)
    0.26
    (0.829)
    -4.49
    (0.852)
    -3.65
    (0.833)
    -2.73
    (0.814)
    Week 20 (n=150, 142, 148, 155)
    -1.02
    (0.844)
    -4.56
    (0.868)
    -4.61
    (0.848)
    -3.06
    (0.829)
    Week 26 (n=150, 142, 148, 155)
    -0.47
    (0.755)
    -4.06
    (0.776)
    -3.86
    (0.759)
    -3.72
    (0.742)
    15. Secondary Outcome
    Title Change From Baseline in Proinsulin/Insulin Ratio
    Description The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20 and 26 relative to the Baseline value. Least squares means were from an ANCOVA model with treatment and geographic region as class variables and Baseline proinsulin/insulin ratio as a covariate.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 4 (n=135, 133, 133, 145)
    -0.073
    (0.0150)
    -0.047
    (0.0151)
    -0.080
    (0.0151)
    -0.056
    (0.0144)
    Week 8 (n=149, 142, 146, 155)
    -0.041
    (0.0140)
    -0.085
    (0.0144)
    -0.094
    (0.0142)
    -0.102
    (0.0138)
    Week 12 (n=149, 142, 147, 155)
    -0.062
    (0.0122)
    -0.098
    (0.0125)
    -0.123
    (0.0123)
    -0.095
    (0.0120)
    Week 16 (n=149, 142, 147, 155)
    -0.049
    (0.0173)
    -0.081
    (0.0177)
    -0.115
    (0.0174)
    -0.090
    (0.0170)
    Week 20 (n=149, 142, 147, 155)
    -0.057
    (0.0173)
    -0.076
    (0.0177)
    -0.124
    (0.0174)
    -0.119
    (0.0169)
    Week 26 (n=149, 142, 147, 155)
    -0.051
    (0.0145)
    -0.076
    (0.0148)
    -0.107
    (0.0146)
    -0.102
    (0.0142)
    16. Secondary Outcome
    Title Change From Baseline in C-peptide Levels
    Description C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline C-peptide as a covariate.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 4 (n=142, 141, 141, 146)
    0.057
    (0.0740)
    -0.551
    (0.0741)
    -0.593
    (0.0741)
    -0.452
    (0.0729)
    Week 8 (n=158, 150, 153, 156)
    0.034
    (0.0701)
    -0.606
    (0.0718)
    -0.620
    (0.0711)
    -0.547
    (0.0704)
    Week 12 (n=158, 150, 154, 156)
    -0.040
    (0.0676)
    -0.612
    (0.0693)
    -0.534
    (0.0684)
    -0.536
    (0.0680)
    Week 16 (n=158, 150, 154, 156)
    0.037
    (0.0801)
    -0.604
    (0.0822)
    -0.424
    (0.0810)
    -0.353
    (0.0805)
    Week 20 (n=158, 150, 154, 156)
    -0.097
    (0.0783)
    -0.623
    (0.0803)
    -0.556
    (0.0792)
    -0.374
    (0.0787)
    Week 26 (n=158, 150, 154, 156)
    -0.068
    (0.0752)
    -0.577
    (0.0771)
    -0.541
    (0.0760)
    -0.444
    (0.0756)
    17. Secondary Outcome
    Title Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance
    Description The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5 A higher number indicates a greater degree of insulin resistance. The change from Baseline in HOMA IR was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HOMA IR as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=139, 132, 137, 143)
    -0.814
    (0.5309)
    -3.479
    (0.5458)
    -2.905
    (0.5348)
    -3.877
    (0.5236)
    Week 26 (n=145, 134, 144, 148)
    -1.353
    (0.3566)
    -3.350
    (0.3717)
    -3.646
    (0.3579)
    -3.508
    (0.3532)
    18. Secondary Outcome
    Title Change From Baseline in Homeostatic Model Assessment Beta Cell Function
    Description The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5 The change from Baseline in the homeostasis model assessment of beta cell function was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HOMA beta cell function as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n= 139, 132, 137, 143)
    15.133
    (4.2787)
    17.328
    (4.3868)
    30.266
    (4.3006)
    22.134
    (4.2098)
    Week 26 (n=145, 134, 144, 148)
    10.472
    (8.5306)
    17.500
    (8.8718)
    39.153
    (8.5455)
    24.887
    (8.4285)
    19. Secondary Outcome
    Title Change From Baseline in Body Weight
    Description Change from Baseline in body weight was assessed at Weeks 8, 12, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and Baseline weight as a covariate.
    Time Frame Baseline and Weeks 8, 12, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 8 (n=155, 146, 152, 151)
    -0.34
    (0.184)
    0.58
    (0.189)
    0.82
    (0.185)
    0.70
    (0.186)
    Week 12 (n=159, 147, 155, 154)
    -0.78
    (0.227)
    0.96
    (0.236)
    1.35
    (0.230)
    1.22
    (0.230)
    Week 20 (n=159, 147, 155, 154)
    -0.47
    (0.265)
    1.56
    (0.275)
    2.36
    (0.268)
    1.86
    (0.269)
    Week 26 (n=159, 147, 155, 154)
    -0.29
    (0.291)
    2.19
    (0.302)
    3.14
    (0.295)
    2.51
    (0.296)
    20. Secondary Outcome
    Title Change From Baseline in Total Cholesterol Level
    Description Change from Baseline in total cholesterol level was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline total cholesterol as a covariate.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 4 (n=146, 144, 142, 149)
    -8.5
    (2.22)
    0.9
    (2.23)
    -0.4
    (2.25)
    -5.3
    (2.20)
    Week 8 (n=160, 151, 154, 158)
    -5.4
    (2.30)
    7.2
    (2.37)
    -0.3
    (2.34)
    -1.2
    (2.31)
    Week 12 (n=160, 151, 155, 158)
    -4.0
    (2.43)
    4.9
    (2.51)
    -0.6
    (2.47)
    4.4
    (2.45)
    Week 16 (n=160, 151, 155, 158)
    -4.3
    (2.42)
    4.6
    (2.49)
    3.8
    (2.46)
    4.7
    (2.44)
    Week 20 (n=160, 151, 155, 158)
    -2.9
    (2.67)
    4.5
    (2.75)
    -0.3
    (2.71)
    -0.6
    (2.69)
    Week 26 (n=160, 151, 155, 158)
    -0.5
    (2.61)
    6.5
    (2.68)
    3.7
    (2.65)
    4.0
    (2.62)
    21. Secondary Outcome
    Title Change From Baseline in Low-Density Lipoprotein Cholesterol
    Description Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline LDL cholesterol as a covariate.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 4 (n=137, 130, 135, 142)
    -3.5
    (1.88)
    2.8
    (1.93)
    2.2
    (1.89)
    -2.8
    (1.85)
    Week 8 (n=152, 139, 147, 153)
    -0.5
    (1.96)
    7.6
    (2.05)
    2.6
    (1.99)
    1.3
    (1.95)
    Week 12 (n=154, 140, 148, 154)
    0.8
    (2.02)
    5.8
    (2.12)
    1.4
    (2.06)
    3.9
    (2.02)
    Week 16 (n=154, 140, 148, 154)
    1.8
    (2.22)
    6.6
    (2.33)
    5.3
    (2.27)
    4.6
    (2.22)
    Week 20 (n=154, 140, 148, 154)
    0.9
    (2.27)
    7.4
    (2.38)
    2.1
    (2.32)
    0.5
    (2.27)
    Week 26 (n=154, 140, 148, 154)
    2.0
    (2.22)
    8.1
    (2.33)
    4.6
    (2.27)
    3.8
    (2.22)
    22. Secondary Outcome
    Title Change From Baseline in High-Density Lipoprotein Cholesterol
    Description Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HDL cholesterol as a covariate.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 4 (n=146, 144, 142, 149)
    -0.2
    (0.54)
    3.0
    (0.54)
    3.8
    (0.55)
    3.0
    (0.54)
    Week 8 (n=160, 151, 154, 158)
    0.5
    (0.56)
    4.7
    (0.58)
    5.0
    (0.57)
    4.8
    (0.57)
    Week 12 (n=160, 151, 155, 158)
    0.9
    (0.64)
    6.0
    (0.66)
    6.4
    (0.65)
    6.5
    (0.65)
    Week 16 (n=160, 151, 155, 158)
    0.9
    (0.57)
    5.2
    (0.58)
    6.0
    (0.58)
    5.9
    (0.57)
    Week 20 (n=160, 151, 155, 158)
    0.5
    (0.59)
    4.7
    (0.60)
    5.6
    (0.60)
    5.6
    (0.59)
    Week 26 (n=160, 151, 155, 158)
    0.8
    (0.64)
    5.7
    (0.66)
    6.2
    (0.65)
    6.2
    (0.64)
    23. Secondary Outcome
    Title Change From Baseline in Triglyceride Levels
    Description Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline triglycerides as a covariate.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 4 (n=146, 144, 142, 149)
    -28.2
    (8.60)
    -43.2
    (8.63)
    -51.7
    (8.70)
    -32.1
    (8.51)
    Week 8 (n=160, 151, 154, 158)
    -34.8
    (6.51)
    -38.2
    (6.69)
    -61.6
    (6.63)
    -51.9
    (6.56)
    Week 12 (n=160, 151, 155, 158)
    -36.4
    (6.90)
    -47.9
    (7.09)
    -64.3
    (7.00)
    -45.4
    (6.95)
    Week 16 (n=160, 151, 155, 158)
    -44.5
    (5.74)
    -48.3
    (5.90)
    -54.6
    (5.82)
    -43.9
    (5.78)
    Week 20 (n=160, 151, 155, 158)
    -29.9
    (7.35)
    -46.6
    (7.56)
    -59.3
    (7.46)
    -46.5
    (7.41)
    Week 26 (n=160, 151, 155, 158)
    -24.7
    (6.83)
    -46.6
    (7.02)
    -56.2
    (6.92)
    -43.1
    (6.88)
    24. Secondary Outcome
    Title Change From Baseline in Free Fatty Acids
    Description Change from Baseline in free fatty acids (FFA) was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline free fatty acid as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=148, 136, 140, 147)
    -0.0404
    (0.01643)
    -0.0990
    (0.01716)
    -0.1061
    (0.01690)
    -0.0805
    (0.01650)
    Week 26 (n=154, 136, 147, 150)
    -0.0429
    (0.01624)
    -0.0680
    (0.01729)
    -0.0881
    (0.01662)
    -0.1013
    (0.01647)
    25. Secondary Outcome
    Title Change From Baseline in Plasminogen Activator Inhibitor-1
    Description Change from Baseline in plasminogen activator inhibitor-1 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline plasminogen activator inhibitor-1 as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=136, 127, 131, 133)
    -1.58
    (2.815)
    -4.23
    (2.909)
    -9.63
    (2.870)
    -11.87
    (2.849)
    Week 26 (n=145, 129, 142, 137)
    1.71
    (3.151)
    -5.45
    (3.341)
    -7.14
    (3.189)
    -8.38
    (3.246)
    26. Secondary Outcome
    Title Change From Baseline in High-sensitivity C-Reactive Protein
    Description Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline hsCRP as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=147, 134, 138, 146)
    -0.4497
    (0.41497)
    -1.7446
    (0.43493)
    -1.5346
    (0.42831)
    -2.2771
    (0.41646)
    Week 26 (n=153, 135, 144, 149)
    -0.1851
    (0.42623)
    -1.0391
    (0.45388)
    -1.9763
    (0.43925)
    -1.9796
    (0.43182)
    27. Secondary Outcome
    Title Change From Baseline in Adiponectin
    Description Change from Baseline in adiponectin was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline adiponectin as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=148, 137, 141, 147)
    -0.28
    (0.560)
    6.35
    (0.582)
    8.10
    (0.575)
    7.50
    (0.562)
    Week 26 (n=154, 137, 147, 149)
    -0.09
    (0.570)
    6.90
    (0.605)
    6.85
    (0.586)
    7.16
    (0.581)
    28. Secondary Outcome
    Title Change From Baseline in Apolipoprotein A1
    Description Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and Baseline apolipoprotein A1 as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=140, 138, 137, 144)
    -1.6
    (1.57)
    2.3
    (1.58)
    1.0
    (1.59)
    1.7
    (1.55)
    Week 26 (n=149, 139, 146, 146)
    -4.5
    (1.59)
    1.2
    (1.64)
    0.8
    (1.60)
    1.6
    (1.60)
    29. Secondary Outcome
    Title Change From Baseline in Apolipoprotein A2
    Description Change from Baseline in apolipoprotein A2 was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein A2 as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=140, 138, 137, 144)
    -0.1
    (0.41)
    3.4
    (0.41)
    2.8
    (0.41)
    3.2
    (0.40)
    Week 26 (n=149, 139, 146, 146)
    -0.3
    (0.41)
    2.9
    (0.43)
    2.5
    (0.42)
    2.6
    (0.42)
    30. Secondary Outcome
    Title Change From Baseline in Apolipoprotein B
    Description Change from Baseline in apolipoprotein B was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein B as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=140, 138, 137, 143)
    -4.0
    (1.76)
    -5.0
    (1.78)
    -9.8
    (1.78)
    -5.9
    (1.74)
    Week 26 (n=149, 139, 146, 146)
    -2.5
    (1.84)
    -3.7
    (1.91)
    -7.9
    (1.86)
    -6.4
    (1.86)
    31. Secondary Outcome
    Title Change From Baseline in Apolipoprotein C-III
    Description Change from Baseline in apolipoprotein C-III was assessed at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline apolipoprotein C-III as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=140, 138, 138, 144)
    -0.5
    (0.30)
    -0.3
    (0.30)
    -0.8
    (0.30)
    -0.3
    (0.30)
    Week 26 (n=149, 139, 147, 146)
    -0.4
    (0.28)
    -0.2
    (0.29)
    -0.3
    (0.28)
    -0.4
    (0.28)
    32. Secondary Outcome
    Title Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides
    Description Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline NMR total triglycerides as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 147 133 141 147
    Week 12 (n=139, 132, 132, 141)
    -14.9
    (6.36)
    -25.0
    (6.52)
    -39.7
    (6.52)
    -23.7
    (6.32)
    Week 26 (n=147, 133, 141, 147)
    -7.6
    (5.82)
    -20.2
    (6.11)
    -28.8
    (5.94)
    -22.6
    (5.82)
    33. Secondary Outcome
    Title Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles
    Description The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL/chylomicron particles as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Total Particles - Week 12 (n=139, 132, 132, 141)
    -6.59
    (2.600)
    0.70
    (2.663)
    -9.63
    (2.664)
    -2.67
    (2.578)
    Total Particles - Week 26 (n=147, 133, 141, 147)
    -4.97
    (2.831)
    4.94
    (2.976)
    -0.73
    (2.888)
    -1.17
    (2.828)
    Large Particles - Week 12 (n=139, 132, 132, 141)
    -0.94
    (0.511)
    -1.83
    (0.525)
    -2.63
    (0.525)
    -2.06
    (0.508)
    Large Particles - Week 26 (n=147, 133, 141, 147)
    -0.18
    (0.480)
    -1.96
    (0.505)
    -2.37
    (0.490)
    -2.11
    (0.480)
    34. Secondary Outcome
    Title Change From Baseline in VLDL / Chylomicron Triglycerides
    Description The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL/chylomicron triglycerides as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=139, 132, 132, 141)
    -14.4
    (6.34)
    -25.6
    (6.50)
    -39.5
    (6.50)
    -24.2
    (6.30)
    Week 26 (n=147, 133, 141, 147)
    -8.2
    (5.79)
    -22.0
    (6.08)
    -29.7
    (5.90)
    -23.3
    (5.79)
    35. Secondary Outcome
    Title Change From Baseline in VLDL Particles
    Description The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline VLDL particles as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Medium Particles - Week 12 (n=139, 132, 132, 141)
    -3.20
    (1.639)
    -2.30
    (1.678)
    -8.52
    (1.679)
    -4.69
    (1.625)
    Medium Particles - Week 26 (n=147, 133, 141, 147)
    -0.23
    (1.784)
    -0.39
    (1.874)
    -3.76
    (1.819)
    -3.58
    (1.782)
    Small Particles - Week 12 (n=139, 132, 132, 141)
    -1.74
    (1.617)
    4.77
    (1.662)
    1.18
    (1.660)
    3.71
    (1.607)
    Small Particles - Week 26 (n=147, 133, 141, 147)
    -4.11
    (1.710)
    7.16
    (1.802)
    5.22
    (1.746)
    4.36
    (1.711)
    36. Secondary Outcome
    Title Change From Baseline in Mean VLDL Particle Size
    Description Change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean VLDL particle size as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=139, 132, 132, 141)
    -0.97
    (0.668)
    -3.97
    (0.688)
    -2.92
    (0.687)
    -2.85
    (0.665)
    Week 26 (n=147, 133, 141, 147)
    0.30
    (0.607)
    -3.71
    (0.640)
    -4.21
    (0.620)
    -2.80
    (0.607)
    37. Secondary Outcome
    Title Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles
    Description The change from Baseline in levels of IDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline IDL particles as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=139, 132, 132, 141)
    -2.9
    (3.63)
    -1.0
    (3.72)
    -2.9
    (3.73)
    -4.0
    (3.61)
    Week 26 (n=147, 133, 141, 147)
    0.5
    (3.68)
    2.1
    (3.86)
    -1.0
    (3.75)
    -5.8
    (3.68)
    38. Secondary Outcome
    Title Change From Baseline in Low Density Lipoprotein (LDL) Particles
    Description The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline LDL particles as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Total Particles - Week 12 (n=139, 132, 132, 141)
    -11.9
    (28.57)
    -104.1
    (29.34)
    -207.0
    (29.33)
    -181.8
    (28.40)
    Total Particles - Week 26 (n=147, 133, 141, 147)
    60.9
    (30.67)
    -75.6
    (32.29)
    -169.9
    (31.31)
    -177.1
    (30.68)
    Large Particles - Week 12 (n=139, 132, 132, 141)
    15.3
    (15.16)
    98.8
    (15.52)
    129.4
    (15.54)
    142.1
    (15.05)
    Large Particles - Week 26 (n=147, 133, 141, 147)
    2.6
    (15.32)
    120.4
    (16.10)
    146.6
    (15.63)
    155.5
    (15.33)
    Medium-Small - Week 12 (n=139, 132, 132, 141)
    -6.2
    (6.25)
    -41.4
    (6.41)
    -65.8
    (6.41)
    -65.8
    (6.20)
    Medium-Small - Week 26 (n=147, 133, 141, 147)
    9.9
    (6.42)
    -40.1
    (6.75)
    -63.0
    (6.55)
    -66.6
    (6.41)
    Total Small - Week 12 (n=139, 132, 132, 141)
    -27.8
    (31.91)
    -200.3
    (32.71)
    -331.2
    (32.73)
    -320.0
    (31.66)
    Total Small - Week 26 (n=147, 133, 141, 147)
    54.5
    (33.34)
    -195.8
    (35.04)
    -313.8
    (34.01)
    -327.4
    (33.30)
    Very Small - Week 12 (n=139, 132, 132, 141)
    -20.9
    (26.22)
    -159.2
    (26.88)
    -265.7
    (26.90)
    -254.2
    (26.02)
    Very Small - Week 26 (n=147, 133, 141, 147)
    45.1
    (27.44)
    -156.0
    (28.83)
    -250.9
    (27.98)
    -260.8
    (27.40)
    39. Secondary Outcome
    Title Change From Baseline in Mean LDL Particle Size
    Description Change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean LDL particle size as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=139, 132, 132, 141)
    0.09
    (0.051)
    0.44
    (0.053)
    0.63
    (0.053)
    0.58
    (0.051)
    Week 26 (n=147, 133, 141, 147)
    -0.02
    (0.052)
    0.44
    (0.054)
    0.65
    (0.053)
    0.61
    (0.052)
    40. Secondary Outcome
    Title Change From Baseline in High Density Lipoprotein (HDL) Particles
    Description The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline HDL particles as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Total Particles - Week 12 (n=139, 132, 132, 141)
    0.18
    (0.350)
    0.92
    (0.359)
    0.11
    (0.359)
    0.54
    (0.348)
    Total Particles - Week 26 (n=147, 133, 141, 147)
    0.81
    (0.359)
    1.67
    (0.377)
    1.01
    (0.367)
    1.03
    (0.359)
    Large Particles - Week 12 (n=139, 132, 132, 141)
    0.07
    (0.195)
    0.99
    (0.200)
    0.98
    (0.200)
    1.31
    (0.193)
    Large Particles - Week 26 (n=147, 133, 141, 147)
    -0.06
    (0.197)
    1.14
    (0.207)
    1.24
    (0.201)
    1.31
    (0.197)
    Medium Particles - Week 12 (n=139, 132, 132, 141)
    -0.26
    (0.311)
    0.72
    (0.319)
    1.60
    (0.320)
    1.61
    (0.308)
    Medium Particles - Week 26 (n=147, 133, 141, 147)
    -0.26
    (0.313)
    0.95
    (0.329)
    1.19
    (0.320)
    1.30
    (0.312)
    Small Particles - Week 12 (n=139, 132, 132, 141)
    0.50
    (0.412)
    -0.68
    (0.423)
    -2.65
    (0.423)
    -2.42
    (0.410)
    Small Particles - Week 26 (n=147, 133, 141, 147)
    1.24
    (0.412)
    -0.28
    (0.433)
    -1.58
    (0.421)
    -1.63
    (0.413)
    41. Secondary Outcome
    Title Change From Baseline in Mean HDL Particle Size
    Description Change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26. Least squares means are from an ANCOVA model with treatment and geographic region as class variables and baseline mean HDL particle size as a covariate.
    Time Frame Baseline and Weeks 12 and 26.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set where Baseline and at least 1 postbaseline value were available. Last observation carried forward (LOCF) imputation was utilized.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    Measure Participants 164 163 164 163
    Week 12 (n=139, 132, 132, 141)
    -0.02
    (0.024)
    0.09
    (0.025)
    0.17
    (0.025)
    0.15
    (0.024)
    Week 26 (n=147, 133, 141, 147)
    -0.03
    (0.024)
    0.08
    (0.025)
    0.15
    (0.024)
    0.14
    (0.024)

    Adverse Events

    Time Frame Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment.
    Adverse Event Reporting Description At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
    Arm/Group Title Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
    All Cause Mortality
    Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/164 (0.6%) 6/163 (3.7%) 8/164 (4.9%) 1/163 (0.6%)
    Cardiac disorders
    Acute myocardial infarction 0/164 (0%) 0/163 (0%) 1/164 (0.6%) 0/163 (0%)
    Angina unstable 1/164 (0.6%) 0/163 (0%) 0/164 (0%) 0/163 (0%)
    Eye disorders
    Retinal detachment 0/164 (0%) 0/163 (0%) 1/164 (0.6%) 0/163 (0%)
    Gastrointestinal disorders
    Gastritis 0/164 (0%) 0/163 (0%) 1/164 (0.6%) 0/163 (0%)
    Pancreatitis 0/164 (0%) 0/163 (0%) 1/164 (0.6%) 0/163 (0%)
    General disorders
    Non-cardiac chest pain 0/164 (0%) 1/163 (0.6%) 0/164 (0%) 0/163 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/164 (0%) 0/163 (0%) 1/164 (0.6%) 0/163 (0%)
    Infections and infestations
    Cervicitis 0/164 (0%) 0/163 (0%) 1/164 (0.6%) 0/163 (0%)
    Metabolism and nutrition disorders
    Hypertriglyceridaemia 0/164 (0%) 1/163 (0.6%) 0/164 (0%) 0/163 (0%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain 0/164 (0%) 1/163 (0.6%) 0/164 (0%) 0/163 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon cancer 0/164 (0%) 1/163 (0.6%) 0/164 (0%) 0/163 (0%)
    Nervous system disorders
    Syncope 0/164 (0%) 1/163 (0.6%) 1/164 (0.6%) 0/163 (0%)
    Cerebral ischaemia 0/164 (0%) 1/163 (0.6%) 0/164 (0%) 0/163 (0%)
    Renal and urinary disorders
    Haematuria 0/164 (0%) 0/163 (0%) 1/164 (0.6%) 0/163 (0%)
    Reproductive system and breast disorders
    Endometriosis 0/164 (0%) 0/163 (0%) 0/164 (0%) 1/163 (0.6%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 0/164 (0%) 0/163 (0%) 1/164 (0.6%) 0/163 (0%)
    Vascular disorders
    Aortic stenosis 0/164 (0%) 0/163 (0%) 1/164 (0.6%) 0/163 (0%)
    Other (Not Including Serious) Adverse Events
    Alogliptin 25 mg Pioglitazone 30 mg Alogliptin 25 mg + Pioglitazone 30 mg Alogliptin 12.5 mg + Pioglitazone 30 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/164 (11.6%) 25/163 (15.3%) 37/164 (22.6%) 24/163 (14.7%)
    General disorders
    Oedema peripheral 2/164 (1.2%) 9/163 (5.5%) 4/164 (2.4%) 2/163 (1.2%)
    Infections and infestations
    Urinary tract infection 5/164 (3%) 4/163 (2.5%) 9/164 (5.5%) 6/163 (3.7%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/164 (0.6%) 3/163 (1.8%) 10/164 (6.1%) 3/163 (1.8%)
    Nervous system disorders
    Headache 11/164 (6.7%) 11/163 (6.7%) 20/164 (12.2%) 14/163 (8.6%)

    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:
    NCT00395512
    Other Study ID Numbers:
    • 01-06-TL-322OPI-002
    • 2006-005492-17
    • U1111-1113-8616
    First Posted:
    Nov 3, 2006
    Last Update Posted:
    Mar 27, 2013
    Last Verified:
    Feb 1, 2013