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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00432276
First received: February 5, 2007
Last updated: April 1, 2013
Last verified: April 2013
  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.


Condition Intervention Phase
Diabetes Mellitus
Drug: Alogliptin
Drug: Pioglitazone
Drug: Metformin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change 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).


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:

    1. After more than 2 weeks of treatment but prior to the Week 4 Visit: A single fasting plasma glucose (FPG) ≥275 mg/dL;
    2. From the Week 4 Visit but prior to the Week 8 Visit: A single FPG ≥250 mg/dL;
    3. From the Week 8 Visit but prior to the Week 12 Visit: A single FPG ≥225 mg/dL;
    4. 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.


Enrollment: 803
Study Start Date: January 2007
Study Completion Date: June 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Alogliptin
Alogliptin tablets.
Other Name: SYR-322
Drug: Pioglitazone
Pioglitazone tablets.
Other Name: ACTOS®
Drug: Metformin
Metformin HCl tablets (immediate-release, commercially available formulation) ≥1500 mg or maximum tolerated dose.
Drug: Placebo
Matching placebo tablets.
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.
Drug: Pioglitazone
Pioglitazone tablets.
Other Name: ACTOS®
Drug: Metformin
Metformin HCl tablets (immediate-release, commercially available formulation) ≥1500 mg or maximum tolerated dose.
Drug: Placebo
Matching placebo tablets.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00432276

  Show 86 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: VP Biological Sciences Takeda
  More Information

Additional Information:
Publications:
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00432276     History of Changes
Other Study ID Numbers: 01-06-TL-322OPI-004, 2006-006025-73, U1111-1112-3363
Study First Received: February 5, 2007
Results First Received: February 19, 2013
Last Updated: April 1, 2013
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council
Austria: Agency for Health and Food Safety
Austria: Ethikkommission
Austria: Federal Ministry for Health and Women
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Institutional Review Board
Belgium: Ministry of Social Affairs, Public Health and the Environment
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee
Denmark: National Board of Health
Denmark: The Danish National Committee on Biomedical Research Ethics
Denmark: The Ministry of the Interior and Health
Denmark: The Regional Committee on Biomedical Research Ethics
Finland: Ethics Committee
Finland: Ministry of Social Affairs and Health
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Direction Générale de la Santé
France: French Data Protection Authority
France: Institutional Ethical Committee
France: Ministry of Health
France: National Consultative Ethics Committee for Health and Life Sciences
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Germany: Federal Ministry of Education and Research
Germany: Federal Ministry of Food, Agriculture and Consumer Protection
Germany: German Institute of Medical Documentation and Information
Germany: Ministry of Health
Germany: Paul-Ehrlich-Institut
Greece: Ethics Committee
Greece: Ministry of Health and Welfare
Greece: National Organization of Medicines
India: Central Drugs Standard Control Organization
India: Department of Atomic Energy
India: Drugs Controller General of India
India: Indian Council of Medical Research
India: Institutional Review Board
India: Ministry of Health
India: Ministry of Science and Technology
India: Science and Engineering Research Council
Italy: Ethics Committee
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
Netherlands: Independent Ethics Committee
Netherlands: Dutch Health Care Inspectorate
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: Medicines Evaluation Board (MEB)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Food Safety Authority
New Zealand: Health Research Council
New Zealand: Health and Disability Ethics Committees
New Zealand: Institutional Review Board
New Zealand: Medsafe
Norway: Data Protection Authority
Norway: Directorate of Health
Norway: Norwegian Institute of Public Health
Norway: Norwegian Medicines Agency
Norway: Norwegian Social Science Data Services
Norway:National Committee for Medical and Health Research Ethics
Romania: Ministry of Public Health
Romania: National Medicines Agency
Romania: State Institute for Drug Control
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Russia: Pharmacological Committee, Ministry of Health
South Africa: Department of Health
South Africa: Medicines Control Council
South Africa: National Health Research Ethics Council
South Korea: Institutional Review Board
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Comité Ético de Investigación Clínica
Spain: Ethics Committee
Spain: Ministry of Health
Spain: Ministry of Health and Consumption
Spain: Spanish Agency of Medicines
Switzerland: Ethikkommission
Switzerland: Federal Office of Public Health
Switzerland: Laws and standards
Switzerland: Swissmedic
United Kingdom: Department of Health
United Kingdom: Food Standards Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee
United Nations: International Atomic Energy Agency
United States: Federal Government
United States: Institutional Review Board
Latvia: State Agency of Medicines
Sweden: Institutional Review Board
Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board
Sweden: Swedish National Council on Medical Ethics
Sweden: Swedish Research Council
Sweden: The National Board of Health and Welfare

Keywords provided by Takeda:
Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus, Lipoatrophic
Dyslipidemia
Hyperglycemia
Drug Therapy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Alogliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 31, 2014