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

Primary Purpose

Diabetes Mellitus

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Alogliptin

Pioglitazone

Metformin

Placebo

About this trial

This is an interventional treatment trial for Diabetes Mellitus focused on measuring Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Hyperglycemia, Drug Therapy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Alogliptin 25 mg + Pioglitazone 30 mg add-on to Metformin

Pioglitazone 45 mg add-on to Metformin

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change From Baseline in Glycosylated Hemoglobin (HbA1c)

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

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%

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%

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%

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%

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%

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%

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%

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

Full Information

NCT ID

NCT00432276

First Posted

February 5, 2007

Last Updated

April 1, 2013

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT00432276

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2013

Overall Recruitment Status

Completed

Study Start Date

January 2007 (undefined)

Primary Completion Date

May 2009 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus

Keywords

Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Hyperglycemia, Drug Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

803 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Alogliptin 25 mg + Pioglitazone 30 mg add-on to Metformin

Arm Type

Experimental

Arm Description

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.

Arm Title

Pioglitazone 45 mg add-on to Metformin

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Alogliptin

Other Intervention Name(s)

SYR-322

Intervention Description

Alogliptin tablets.

Intervention Type

Drug

Intervention Name(s)

Pioglitazone

Other Intervention Name(s)

ACTOS®

Intervention Description

Pioglitazone tablets.

Intervention Type

Drug

Intervention Name(s)

Metformin

Intervention Description

Metformin HCl tablets (immediate-release, commercially available formulation) ≥1500 mg or maximum tolerated dose.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo tablets.

Primary Outcome Measure Information:

Title

Change From Baseline in Glycosylated Hemoglobin (HbA1c)

Description

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).

Time Frame

Baseline and Weeks 26 and 52.

Secondary Outcome Measure Information:

Title

Change From Baseline in HbA1c Over Time

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 34 and 42.

Title

Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5%

Description

Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.

Time Frame

Weeks 26 and 52.

Title

Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0%

Description

Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 7%.

Time Frame

Weeks 26 and 52.

Title

Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5%

Description

Clinical response at Weeks 26 and 52 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.

Time Frame

Weeks 26 and 52.

Title

Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5%

Description

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%.

Time Frame

Weeks 26 and 52.

Title

Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.0%

Description

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%.

Time Frame

Weeks 26 and 52.

Title

Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5%

Description

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%.

Time Frame

Weeks 26 and 52.

Title

Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0%

Description

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%.

Time Frame

Weeks 26 and 52.

Title

Change From Baseline in Fasting Plasma Glucose

Description

Time Frame

Baseline and Weeks 2, 4, 8, 12, 16, 20, 26, 34, 42 and 52.

Title

Percentage of Participants With Marked Hyperglycemia

Description

Marked Hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).

Time Frame

Baseline to Week 52

Title

Percentage of Participants Meeting Hyperglycemic Rescue Criteria

Description

Time Frame

Baseline to Week 52

Title

Change From Baseline in Fasting Proinsulin

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.

Title

Change From Baseline in Fasting Insulin

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.

Title

Change From Baseline in Proinsulin/Insulin Ratio

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.

Title

Change From Baseline in C-peptide

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.

Title

Change From Baseline in Calculated HOMA Insulin Resistance

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Calculated HOMA Beta-cell Function

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Body Weight

Description

Time Frame

Baseline and Weeks 4, 8, 12, 26, 42 and 52.

Title

Change From Baseline in Total Cholesterol

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.

Title

Change From Baseline in High-Density Lipoprotein Cholesterol

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.

Title

Change From Baseline in Low-Density Lipoprotein Cholesterol

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.

Title

Change From Baseline in Triglycerides

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 26, 34, 42 and 52.

Title

Change From Baseline in Free Fatty Acids

Description

Time Frame

Baseline and Weeks 12, 26, 42, and 52.

Title

Change From Baseline in Apolipoprotein A1

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Apolipoprotein A2

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Apolipoprotein B

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Apolipoprotein C-III

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Plasminogen Activator Inhibitor-1

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in High-sensitivity C-Reactive Protein

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Adiponectin

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in VLDL / Chylomicron Triglycerides

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in VLDL Particles

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Mean VLDL Particle Size

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Low Density Lipoprotein (LDL) Particles

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Mean LDL Particle Size

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in High Density Lipoprotein (HDL) Particles

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

Title

Change From Baseline in Mean HDL Particle Size

Description

Time Frame

Baseline and Weeks 12, 26, 42 and 52.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

VP Biological Sciences

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

City

Birmingham

State/Province

Alabama

Country

United States

City

Huntsville

State/Province

Alabama

Country

United States

City

Lake Havasu City

State/Province

Arizona

Country

United States

City

Little Rock

State/Province

Arkansas

Country

United States

City

Foothill Ranch

State/Province

California

Country

United States

City

Los Alamitos

State/Province

California

Country

United States

City

Los Angeles

State/Province

California

Country

United States

City

Pismo Beach

State/Province

California

Country

United States

City

San Diego

State/Province

California

Country

United States

City

Golden

State/Province

Colorado

Country

United States

City

Clearwater

State/Province

Florida

Country

United States

City

Hialeah

State/Province

Florida

Country

United States

City

Lakeland

State/Province

Florida

Country

United States

City

Marianna

State/Province

Florida

Country

United States

City

Miami

State/Province

Florida

Country

United States

City

North Miami Beach

State/Province

Florida

Country

United States

City

Pembroke Pines

State/Province

Florida

Country

United States

City

Sebastian

State/Province

Florida

Country

United States

City

South Miami

State/Province

Florida

Country

United States

City

Tampa

State/Province

Florida

Country

United States

City

Winter Park

State/Province

Florida

Country

United States

City

Blue Ridge

State/Province

Georgia

Country

United States

City

Conyers

State/Province

Georgia

Country

United States

City

Decatur

State/Province

Georgia

Country

United States

City

Duluth

State/Province

Georgia

Country

United States

City

Dunwoody

State/Province

Georgia

Country

United States

City

Warner Robins

State/Province

Georgia

Country

United States

City

Boise

State/Province

Idaho

Country

United States

City

Coeur D'Alene

State/Province

Idaho

Country

United States

City

Burr Ridge

State/Province

Illinois

Country

United States

City

Chicago

State/Province

Illinois

Country

United States

City

Melrose Park

State/Province

Illinois

Country

United States

City

Naperville

State/Province

Illinois

Country

United States

City

O'Fallon

State/Province

Illinois

Country

United States

City

Bloomington

State/Province

Indiana

Country

United States

City

Mishawaka

State/Province

Indiana

Country

United States

City

Overland Park

State/Province

Kansas

Country

United States

City

Marrero

State/Province

Louisiana

Country

United States

City

Elkton

State/Province

Maryland

Country

United States

City

Rockville

State/Province

Maryland

Country

United States

City

Towson

State/Province

Maryland

Country

United States

City

Marlborough

State/Province

Massachusetts

Country

United States

City

Bay City

State/Province

Michigan

Country

United States

City

St. Clair Shores

State/Province

Michigan

Country

United States

City

McCook

State/Province

Nebraska

Country

United States

City

Las Vegas

State/Province

Nevada

Country

United States

City

Blackwood

State/Province

New Jersey

Country

United States

City

Trenton

State/Province

New Jersey

Country

United States

City

West Caldwell

State/Province

New Jersey

Country

United States

City

Asheboro

State/Province

North Carolina

Country

United States

City

Charlotte

State/Province

North Carolina

Country

United States

City

Mooresville

State/Province

North Carolina

Country

United States

City

Shelby

State/Province

North Carolina

Country

United States

City

Sparta

State/Province

North Carolina

Country

United States

City

Bismarck

State/Province

North Dakota

Country

United States

City

Orrville

State/Province

Ohio

Country

United States

City

Norman

State/Province

Oklahoma

Country

United States

City

Ashland

State/Province

Oregon

Country

United States

City

Aliquippa

State/Province

Pennsylvania

Country

United States

City

Altoona

State/Province

Pennsylvania

Country

United States

City

Dawningtown

State/Province

Pennsylvania

Country

United States

City

Fleetwood

State/Province

Pennsylvania

Country

United States

City

Kingston

State/Province

Pennsylvania

Country

United States

City

Norristown

State/Province

Pennsylvania

Country

United States

City

Pittsburgh

State/Province

Pennsylvania

Country

United States

City

Tipton

State/Province

Pennsylvania

Country

United States

City

Florence

State/Province

South Carolina

Country

United States

City

Taylors

State/Province

South Carolina

Country

United States

City

Williamston

State/Province

South Carolina

Country

United States

City

Watertown

State/Province

South Dakota

Country

United States

City

Kingsport

State/Province

Tennessee

Country

United States

City

Milan

State/Province

Tennessee

Country

United States

City

Nashville

State/Province

Tennessee

Country

United States

City

Arlington

State/Province

Texas

Country

United States

City

Austin

State/Province

Texas

Country

United States

City

Colleyville

State/Province

Texas

Country

United States

City

El Paso

State/Province

Texas

Country

United States

City

Garland

State/Province

Texas

Country

United States

City

Houston

State/Province

Texas

Country

United States

City

Hurst

State/Province

Texas

Country

United States

City

San Antonio

State/Province

Texas

Country

United States

City

Seguin

State/Province

Texas

Country

United States

City

Hampton

State/Province

Virginia

Country

United States

City

Norfolk

State/Province

Virginia

Country

United States

City

Richmond

State/Province

Virginia

Country

United States

City

Virginia Beach

State/Province

Virginia

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

21733058

Citation

Bosi E, Ellis GC, Wilson CA, Fleck PR. Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study. Diabetes Obes Metab. 2011 Dec;13(12):1088-96. doi: 10.1111/j.1463-1326.2011.01463.x.

Results Reference

result

Learn more about this trial

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

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