Efficacy of Alogliptin and Pioglitazone in Subjects With Type 2 Diabetes Mellitus

Overview[ - collapse ][ - ]

Purpose The purpose of the study is to compare the effect of adding alogliptin, once daily (QD), to the ongoing treatment regimen of pioglitazone HCl and metformin in patients with inadequate glycemic control.
ConditionDiabetes Mellitus
InterventionDrug: Alogliptin
Drug: Pioglitazone
Drug: Metformin
Drug: Placebo
PhasePhase 3
SponsorTakeda
Responsible PartyTakeda
ClinicalTrials.gov IdentifierNCT00432276
First ReceivedFebruary 5, 2007
Last UpdatedApril 1, 2013
Last verifiedApril 2013

Tracking Information[ + expand ][ + ]

First Received DateFebruary 5, 2007
Last Updated DateApril 1, 2013
Start DateJanuary 2007
Estimated Primary Completion DateJune 2009
Current Primary Outcome MeasuresChange From Baseline in Glycosylated Hemoglobin (HbA1c) [Time Frame: Baseline and Weeks 26 and 52.] [Designated as safety issue: No]The change from Baseline to Week 26 and Week 52 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
Current Secondary Outcome Measures
  • Change From Baseline in HbA1c Over Time [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 34 and 42.] [Designated as safety issue: No]The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) during the study. Least Squares Means were from an Analysis of Covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and baseline metformin dose and baseline HbA1c as covariates.
  • Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% [Time Frame: Weeks 26 and 52.] [Designated as safety issue: No]Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.
  • Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% [Time Frame: Weeks 26 and 52.] [Designated as safety issue: No]Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 7%.
  • Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% [Time Frame: Weeks 26 and 52.] [Designated as safety issue: No]Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.
  • Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% [Time Frame: Weeks 26 and 52.] [Designated as safety issue: No]Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.
  • Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.0% [Time Frame: Weeks 26 and 52.] [Designated as safety issue: No]Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.0%.
  • Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% [Time Frame: Weeks 26 and 52.] [Designated as safety issue: No]Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.
  • Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% [Time Frame: Weeks 26 and 52.] [Designated as safety issue: No]Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%.
  • Change From Baseline in Fasting Plasma Glucose [Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 26, 34, 42 and 52.] [Designated as safety issue: No]The change from Baseline in fasting plasma glucose (FPG) was assessed at Weeks 2, 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least Squares Means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline FPG as covariates.
  • Percentage of Participants With Marked Hyperglycemia [Time Frame: Baseline to Week 52] [Designated as safety issue: No]Marked Hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).
  • Percentage of Participants Meeting Hyperglycemic Rescue Criteria [Time Frame: Baseline to Week 52] [Designated as safety issue: No]Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 7 days after the first sample and analyzed by the central laboratory:
    After more than 2 weeks of treatment but prior to the Week 4 Visit: A single fasting plasma glucose (FPG) ≥275 mg/dL;
    From the Week 4 Visit but prior to the Week 8 Visit: A single FPG ≥250 mg/dL;
    From the Week 8 Visit but prior to the Week 12 Visit: A single FPG ≥225 mg/dL;
    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.
  • Change From Baseline in Fasting Proinsulin [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.] [Designated as safety issue: No]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, 26, 34, 42 and 52. Least Squares Means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting proinsulin as covariates.
  • Change From Baseline in Fasting Insulin [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.] [Designated as safety issue: No]The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least Squares Means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting insulin as covariates.
  • Change From Baseline in Proinsulin/Insulin Ratio [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.] [Designated as safety issue: No]The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52 relative to the Baseline value. Least squares means were from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting proinsulin/insulin ratio as covariates.
  • Change From Baseline in C-peptide [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.] [Designated as safety issue: No]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, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline fasting C-peptide as covariates.
  • Change From Baseline in Calculated HOMA Insulin Resistance [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]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, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HOMA insulin resistance as covariates.
  • Change From Baseline in Calculated HOMA Beta-cell Function [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]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, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as covariates.
  • Change From Baseline in Body Weight [Time Frame: Baseline and Weeks 4, 8, 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in body weight was assessed at Weeks 4, 8, 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline body weight as covariates.
  • Change From Baseline in Total Cholesterol [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.] [Designated as safety issue: No]Change from Baseline in total cholesterol was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as covariates.
  • Change From Baseline in High-Density Lipoprotein Cholesterol [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.] [Designated as safety issue: No]Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as covariates.
  • Change From Baseline in Low-Density Lipoprotein Cholesterol [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.] [Designated as safety issue: No]Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as covariates.
  • Change From Baseline in Triglycerides [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.] [Designated as safety issue: No]Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline triglycerides as covariates.
  • Change From Baseline in Free Fatty Acids [Time Frame: Baseline and Weeks 12, 26, 42, and 52.] [Designated as safety issue: No]Change from Baseline in free fatty acids was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline free fatty acids as covariates.
  • Change From Baseline in Apolipoprotein A1 [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as covariates.
  • Change From Baseline in Apolipoprotein A2 [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in Apolipoprotein A2 was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as covariates.
  • Change From Baseline in Apolipoprotein B [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in Apolipoprotein B was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as covariates.
  • Change From Baseline in Apolipoprotein C-III [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in Apolipoprotein C-III was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as covariates.
  • Change From Baseline in Plasminogen Activator Inhibitor-1 [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in plasminogen activator inhibitor-1 (PAI-1) was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as covariates.
  • Change From Baseline in High-sensitivity C-Reactive Protein [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline hsCRP as covariates.
  • Change From Baseline in Adiponectin [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in adiponectin was assessed at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline adiponectin as covariates.
  • Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline NMR triglycerides as covariates.
  • Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]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, 26, 42 and 52.
    Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline VLDL/chylomicron particles as covariates.
  • Change From Baseline in VLDL / Chylomicron Triglycerides [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52.
    Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline VLDL/chylomicron triglycerides as covariates.
  • Change From Baseline in VLDL Particles [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline VLDL particles as covariates.
  • Change From Baseline in Mean VLDL Particle Size [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as covariates.
  • Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline IDL particles as covariates.
  • Change From Baseline in Low Density Lipoprotein (LDL) Particles [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]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, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline LDL particles as covariates.
  • Change From Baseline in Mean LDL Particle Size [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as covariates.
  • Change From Baseline in High Density Lipoprotein (HDL) Particles [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline HDL particles as covariates.
  • Change From Baseline in Mean HDL Particle Size [Time Frame: Baseline and Weeks 12, 26, 42 and 52.] [Designated as safety issue: No]Change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12, 26, 42 and 52. Least squares means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as covariates.

Descriptive Information[ + expand ][ + ]

Brief TitleEfficacy of Alogliptin and Pioglitazone in Subjects With Type 2 Diabetes Mellitus
Official TitleA Multicenter, Randomized, Double-Blind Study to Determine the Efficacy and Safety of the Addition of SYR-322 25 mg Versus Dose Titration From 30 mg to 45 mg of Pioglitazone HCl (ACTOS®) in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Control on a Combination of Metformin and 30 mg of Pioglitazone HCl Therapy
Brief Summary
The purpose of the study is to compare the effect of adding alogliptin, once daily (QD), to
the ongoing treatment regimen of pioglitazone HCl and metformin in patients with inadequate
glycemic control.
Detailed Description
Despite the introduction of new classes of medications for glycemic control, just over half
of adults with type 2 diabetes mellitus (T2DM) achieve a glycosylated hemoglobin level less
than 7.0%, the American Diabetes Association recommended glycosylated hemoglobin goal. The
rising incidence of type 2 diabetes mellitus along with limitations of the currently
available treatments suggest the need for new therapies for glycemic control along with the
increased requirement for combination therapy in type 2 diabetes mellitus.

Thiazolidinediones increase glucose utilization, decrease gluconeogenesis, and increase
glucose disposal through an incompletely understood mechanism but one associated with
binding of the drug to nuclear receptors known as peroxisome proliferator-activated
receptors-gamma. Peroxisome proliferator-activated receptors-gamma are found in tissues
important for insulin action, such as adipose tissue, skeletal muscle, and the liver. The
greatest concentration of peroxisome proliferator-activated receptors-gamma receptors is in
adipose tissue. Thiazolidinediones reduce insulin resistance by enhancing insulin
sensitivity in muscle cells, adipose tissue, and hepatic cells (inhibiting hepatic
gluconeogenesis) with no direct impact on insulin secretion. Thus, thiazolidinediones
improve glycemic control and result in reduced levels of circulating insulin. Pioglitazone
HCl (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka,
Japan). Pioglitazone depends on the presence of insulin for its mechanism of action.
Worldwide clinical investigation has shown that, as an adjunct to diet and exercise,
pioglitazone improves glycemic control when used as monotherapy, and in combination with
commonly used antidiabetic medications (ie, sulfonylureas, metformin, or insulin).

SYR-322 (alogliptin) is a selective, orally available inhibitor of dipeptidyl peptidase IV
currently in development by Takeda Global Research & Development Center, Inc. as a treatment
for type 2 diabetes mellitus. Dipeptidyl peptidase IV is the primary enzyme involved in the
in vivo degradation of at least 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 β-cells to stimulate glucose-dependent insulin
secretion and regulate β-cell proliferation and cytoprotection. Glucagon-like peptide-1 also
inhibits gastric emptying, glucagon secretion, and food intake. The glucose-lowering actions
of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved
in patients with type 2 diabetes.

Given the complementary mechanisms of action of alogliptin (stimulation of insulin
secretion) and pioglitazone (enhancement of insulin sensitivity) and the absence of
overlapping safety risks, the introduction of this combination therapy in patients with T2DM
could potentially show enhanced glycemic control and allow patients to reach and maintain
their HbA1c goal more effectively.

This study is designed to determine if the addition of alogliptin to a combination of
pioglitazone with metformin can be effective at achieving glycemic control without
increasing safety risks versus the titration of pioglitazone to 45 mg with metformin in
patients with type 2 diabetes mellitus who are experiencing inadequate glycemic control on a
current regimen of metformin.
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
ConditionDiabetes Mellitus
InterventionDrug: Alogliptin
Alogliptin tablets.
Other Names:
SYR-322Drug: Pioglitazone
Pioglitazone tablets.
Other Names:
ACTOS®Drug: Metformin
Metformin HCl tablets (immediate-release, commercially available formulation) ≥1500 mg or maximum tolerated dose.
Drug: Placebo
Matching placebo tablets.
Study Arm (s)
  • Experimental: Alogliptin 25 mg + Pioglitazone 30 mg add-on to Metformin
    Alogliptin 25 mg, tablets, orally, once daily; pioglitazone 30 mg, tablets, orally, once daily; and the maximum tolerated dose of metformin, tablets, orally, for up to 52 weeks.
  • Active Comparator: Pioglitazone 45 mg add-on to Metformin
    Alogliptin placebo-matching tablets, orally, once daily; pioglitazone 45 mg, tablets, orally, once daily; and the maximum tolerated dose of metformin, tablets, orally, for up to 52 weeks.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment803
Estimated Completion DateJune 2009
Estimated Primary Completion DateMay 2009
Eligibility Criteria
Inclusion Criteria:

- Has a historical diagnosis of type 2 diabetes mellitus.

- Meets one of the following:

- Has been inadequately controlled (HbA1c between 7% and 10%, inclusive) on a
stable dose of greater than or equal to 1500 mg (or maximum tolerated dose) of
metformin and 30 mg of pioglitazone

- Has been inadequately controlled (as defined by an HbA1c ≥7.5%) on a combination
therapy including metformin and another oral antidiabetic agent (ie,
sulfonylureas, rosiglitazone maleate, or pioglitazone 15 mg, etc). Subjects on a
combination therapy that included a DPP-4 inhibitor were excluded.

- No treatment with antidiabetic agents other than metformin and pioglitazone.

- Body mass index greater than or equal to 23 kg/m^2 and less than or equal to 45
kg/m^2.

- Fasting plasma C-peptide concentration greater than or equal to 0.8 ng/mL.

- Systolic blood pressure less than 160 mmHg and diastolic pressure less than 100 mmHg.

- Hemoglobin greater than or equal to 12 g/dL for males and greater than or equal to 10
g/dL for females.

- Alanine aminotransferase less than or equal to 2.5 x upper limit of normal.

- Serum creatinine less than 1.5 mg/dL for males and less than 1.4 mg/dL for females.

- Thyroid-stimulating hormone level less than or equal to the upper limit of normal
range and the patient is clinically euthyroid.

- 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.

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

- No major illness or debility that in the investigator's opinion prohibits the patient
from completing the study.

Exclusion Criteria:

- Urine albumin/creatinine ratio of greater than 1000 μg/mg.

- 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 bladder cancer.

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

- Patients with unexplained microscopic hematuria of greater than +1, confirmed by
repeat testing.

- History of treated diabetic gastroparesis.

- History of gastric bypass surgery.

- New York Heart Association Class I-IV heart failure regardless of therapy.

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

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

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

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

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

- History of alcohol abuse or substance abuse within the 2 years prior to Screening.

- Receipt of any investigational drug within the 30 days prior to Screening or a
history of receipt of an investigational antidiabetic drug within the 3 months prior
to Screening.

- Prior treatment in an investigational study of alogliptin.

- Hypersensitive to pioglitazone HCl, metformin, alogliptin or other excipients.

- The patient has donated more than 400 mL of blood within the 90 days prior to
Screening and Pre-Screening, if applicable.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00432276
Other Study ID Numbers01-06-TL-322OPI-004
Has Data Monitoring CommitteeNo
Information Provided ByTakeda
Study SponsorTakeda
CollaboratorsNot Provided
Investigators Study Director: VP Biological Sciences Takeda
Verification DateApril 2013

Locations[ + expand ][ + ]

United States, Alabama
Birmingham, Alabama, United States
United States, Alabama
Huntsville, Alabama, United States
United States, Arizona
Lake Havasu City, Arizona, United States
United States, Arkansas
Little Rock, Arkansas, United States
United States, California
Foothill Ranch, California, United States
United States, California
Los Alamitos, California, United States
United States, California
Los Angeles, California, United States
United States, California
Pismo Beach, California, United States
United States, California
San Diego, California, United States
United States, Colorado
Golden, Colorado, United States
United States, Florida
Clearwater, Florida, United States
United States, Florida
Hialeah, Florida, United States
United States, Florida
Lakeland, Florida, United States
United States, Florida
Marianna, Florida, United States
United States, Florida
Miami, Florida, United States
United States, Florida
North Miami Beach, Florida, United States
United States, Florida
Pembroke Pines, Florida, United States
United States, Florida
Sebastian, Florida, United States
United States, Florida
South Miami, Florida, United States
United States, Florida
Tampa, Florida, United States
United States, Florida
Winter Park, Florida, United States
United States, Georgia
Blue Ridge, Georgia, United States
United States, Georgia
Conyers, Georgia, United States
United States, Georgia
Decatur, Georgia, United States
United States, Georgia
Duluth, Georgia, United States
United States, Georgia
Dunwoody, Georgia, United States
United States, Georgia
Warner Robins, Georgia, United States
United States, Idaho
Boise, Idaho, United States
United States, Idaho
Coeur D'Alene, Idaho, United States
United States, Illinois
Burr Ridge, Illinois, United States
United States, Illinois
Chicago, Illinois, United States
United States, Illinois
Melrose Park, Illinois, United States
United States, Illinois
Naperville, Illinois, United States
United States, Illinois
O'Fallon, Illinois, United States
United States, Indiana
Bloomington, Indiana, United States
United States, Indiana
Mishawaka, Indiana, United States
United States, Kansas
Overland Park, Kansas, United States
United States, Louisiana
Marrero, Louisiana, United States
United States, Maryland
Elkton, Maryland, United States
United States, Maryland
Rockville, Maryland, United States
United States, Maryland
Towson, Maryland, United States
United States, Massachusetts
Marlborough, Massachusetts, United States
United States, Michigan
Bay City, Michigan, United States
United States, Michigan
St. Clair Shores, Michigan, United States
United States, Nebraska
McCook, Nebraska, United States
United States, Nevada
Las Vegas, Nevada, United States
United States, New Jersey
Blackwood, New Jersey, United States
United States, New Jersey
Trenton, New Jersey, United States
United States, New Jersey
West Caldwell, New Jersey, United States
United States, North Carolina
Asheboro, North Carolina, United States
United States, North Carolina
Charlotte, North Carolina, United States
United States, North Carolina
Mooresville, North Carolina, United States
United States, North Carolina
Shelby, North Carolina, United States
United States, North Carolina
Sparta, North Carolina, United States
United States, North Dakota
Bismarck, North Dakota, United States
United States, Ohio
Orrville, Ohio, United States
United States, Oklahoma
Norman, Oklahoma, United States
United States, Oregon
Ashland, Oregon, United States
United States, Pennsylvania
Aliquippa, Pennsylvania, United States
United States, Pennsylvania
Altoona, Pennsylvania, United States
United States, Pennsylvania
Dawningtown, Pennsylvania, United States
United States, Pennsylvania
Fleetwood, Pennsylvania, United States
United States, Pennsylvania
Kingston, Pennsylvania, United States
United States, Pennsylvania
Norristown, Pennsylvania, United States
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
United States, Pennsylvania
Tipton, Pennsylvania, United States
United States, South Carolina
Florence, South Carolina, United States
United States, South Carolina
Taylors, South Carolina, United States
United States, South Carolina
Williamston, South Carolina, United States
United States, South Dakota
Watertown, South Dakota, United States
United States, Tennessee
Kingsport, Tennessee, United States
United States, Tennessee
Milan, Tennessee, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Arlington, Texas, United States
United States, Texas
Austin, Texas, United States
United States, Texas
Colleyville, Texas, United States
United States, Texas
El Paso, Texas, United States
United States, Texas
Garland, Texas, United States
United States, Texas
Houston, Texas, United States
United States, Texas
Hurst, Texas, United States
United States, Texas
San Antonio, Texas, United States
United States, Texas
Seguin, Texas, United States
United States, Virginia
Hampton, Virginia, United States
United States, Virginia
Norfolk, Virginia, United States
United States, Virginia
Richmond, Virginia, United States
United States, Virginia
Virginia Beach, Virginia, United States