Efficacy and Safety of Alogliptin Combined With Pioglitazone in Treating Subjects With Type 2 Diabetes Mellitus.

NCT00328627 | Completed Phase 3 Results

• 3 other identifiers: 01-05-TL-322OPI-0012006-000694-30U1111-1113-8587
• Study Type: interventional
• Target: 1,554
• Locations: 19 countries
• Sites: 90

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of alogliptin, once daily (QD), taken in combination with pioglitazone in adults with type 2 diabetes mellitus.

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes Mellitus, Type 2; Drug Therapy; Diabetes Mellitus, Non Insulin Dependent; Glucose Intolerance; Hyperglycemia

Outcome Measures

Primary Outcomes (2)

• Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis)

  The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The primary analysis compared the groupings (combinations of individual treatment groups) of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone (Pioglitazone Alone).

  Baseline and Week 26

• Change From Baseline to Week 26 in HbA1c

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

  Baseline and Week 26

Secondary Outcomes (154)

• Change From Baseline in HbA1c Over Time (Grouped Analysis)

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

• Change From Baseline to Week 4 in HbA1c

  Baseline and Week 4

• Change From Baseline to Week 8 in HbA1c

  Baseline and Week 8

• Change From Baseline to Week 12 in HbA1c

  Baseline and Week 12

• Change From Baseline to Week 16 in HbA1c

  Baseline and Week 16

Study Arms (12)

Placebo

PLACEBO COMPARATOR

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

Drug: Alogliptin placebo; Drug: Pioglitazone placebo

Alogliptin 12.5 + Placebo

EXPERIMENTAL

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

Drug: Alogliptin; Drug: Pioglitazone placebo

Alogliptin 25 + Placebo

EXPERIMENTAL

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

Drug: Alogliptin; Drug: Pioglitazone placebo

Placebo + Pioglitazone 15

ACTIVE COMPARATOR

Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.

Drug: Pioglitazone

Alogliptin 12.5 + Pioglitazone 15

EXPERIMENTAL

Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.

Drug: Alogliptin; Drug: Pioglitazone

Alogliptin 25 + Pioglitazone 15

EXPERIMENTAL

Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.

Drug: Alogliptin; Drug: Pioglitazone

Placebo + Pioglitazone 30

ACTIVE COMPARATOR

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

Drug: Alogliptin placebo; Drug: Pioglitazone

Alogliptin 12.5 + Pioglitazone 30

EXPERIMENTAL

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

Drug: Alogliptin; Drug: Pioglitazone

Alogliptin 25 + Pioglitazone 30

EXPERIMENTAL

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

Drug: Alogliptin; Drug: Pioglitazone

Placebo + Pioglitazone 45

ACTIVE COMPARATOR

Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.

Drug: Alogliptin placebo; Drug: Pioglitazone

Alogliptin 12.5 + Pioglitazone 45

EXPERIMENTAL

Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.

Drug: Alogliptin; Drug: Pioglitazone

Alogliptin 25 + Pioglitazone 45

EXPERIMENTAL

Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.

Drug: Alogliptin; Drug: Pioglitazone

Interventions

Alogliptin DRUG

Alogliptin tablets.

Also known as: SYR-322

Alogliptin 12.5 + Pioglitazone 15; Alogliptin 12.5 + Pioglitazone 30; Alogliptin 12.5 + Pioglitazone 45; Alogliptin 12.5 + Placebo; Alogliptin 25 + Pioglitazone 15; Alogliptin 25 + Pioglitazone 30; Alogliptin 25 + Pioglitazone 45; Alogliptin 25 + Placebo

Alogliptin placebo DRUG

Alogliptin placebo-matching tablets.

Placebo; Placebo + Pioglitazone 30; Placebo + Pioglitazone 45

Pioglitazone DRUG

Pioglitazone tablets.

Also known as: ACTOS®

Alogliptin 12.5 + Pioglitazone 15; Alogliptin 12.5 + Pioglitazone 30; Alogliptin 12.5 + Pioglitazone 45; Alogliptin 25 + Pioglitazone 15; Alogliptin 25 + Pioglitazone 30; Alogliptin 25 + Pioglitazone 45; Placebo + Pioglitazone 15; Placebo + Pioglitazone 30; Placebo + Pioglitazone 45

Pioglitazone placebo DRUG

Pioglitazone placebo-matching tablets.

Alogliptin 12.5 + Placebo; Alogliptin 25 + Placebo; Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women with a historical diagnosis of type 2 diabetes mellitus who were treated with metformin greater than or equal to 1500 mg alone but were experiencing inadequate glycemic control.
• A stable dose of metformin of greater than or equal to 1500 mg or maximum tolerated dose.
• No treatment with antidiabetic agents other than metformin within the 2 months prior to Screening.
• A body mass index greater than or equal to 23 kg/m\^2 and less than or equal to 45 kg/m\^2.
• Fasting C-peptide greater than or equal to 0.8 ng/mL.
• Regular use of other, non-excluded medications was allowed if a stable dose had been established for at least 4 weeks prior to Screening.
• Systolic blood pressure less than or equal to 160 mmHg and diastolic pressure less than or equal to 100 mmHg.
• Hemoglobin greater than or equal to 12 g/dL for men and greater than or equal to 10 g/dL for women.
• Alanine aminotransferase less than or equal to 2.5 times the upper limit of normal.
• Serum creatinine less than 1.5 mg/dL for men and less than 1.4 mg/dL for women.
• Thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject was 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 prohibited the patient from completing the study.

You may not qualify if:

• Urine albumin/creatinine ratio greater than 113 mg/mmol at Screening.
• A history of cancer, other than squamous cell or basal cell carcinoma of the skin, that had not been in full remission for at least 5 years prior to Screening.
• A history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
• A history of treated diabetic gastroparesis.
• New York Heart Association Class III or 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.
• History of infection with hepatitis B, hepatitis C or human immunodeficiency virus.
• History of a psychiatric disorder that could have affected 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.
• A history of alcohol or substance abuse within 2 years prior to Screening.
• Receipt of any investigational drug within 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within 3 months prior to Screening.
• Previous participation in an investigational study of alogliptin.
• Hypersensitive to pioglitazone, alogliptin, or other excipients.

Sponsors & Collaborators

• Takeda: lead

Study Sites (90)

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Birmingham, Alabama, United States

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Columbiana, Alabama, United States

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Huntsville, Alabama, United States

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Phoenix, Arizona, United States

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Little Rock, Arkansas, United States

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Searcy, Arkansas, United States

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Sherwood, Arkansas, United States

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Burbank, California, United States

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Foothill Ranch, California, United States

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Irvine, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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Temecula, California, United States

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Tustin, California, United States

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Colorado Springs, Colorado, United States

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Washington D.C., District of Columbia, United States

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Hollywood, Florida, United States

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Kissimmee, Florida, United States

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Miami, Florida, United States

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New Port Richey, Florida, United States

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Pembroke Pines, Florida, United States

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Pinellas Park, Florida, United States

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Sarasota, Florida, United States

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Vero Beach, Florida, United States

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Atlanta, Georgia, United States

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Roswell, Georgia, United States

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Savannah, Georgia, United States

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Warner Robins, Georgia, United States

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Chicago, Illinois, United States

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Peoria, Illinois, United States

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Lafayette, Indiana, United States

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South Bend, Indiana, United States

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Waterloo, Iowa, United States

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Munfordville, Kentucky, United States

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Baton Rouge, Louisiana, United States

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Marrero, Louisiana, United States

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Elkridge, Maryland, United States

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Prince Frederick, Maryland, United States

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Towson, Maryland, United States

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Marlborough, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Cadillac, Michigan, United States

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Detroit, Michigan, United States

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Livonia, Michigan, United States

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Kansas City, Missouri, United States

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North Las Vegas, Nevada, United States

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Blackwood, New Jersey, United States

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Trenton, New Jersey, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Statesville, North Carolina, United States

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Gallipolis, Ohio, United States

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Marion, Ohio, United States

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Clinton, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Allentown, Pennsylvania, United States

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Altoona, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Alcoa, Tennessee, United States

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Milan, Tennessee, United States

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Morristown, Tennessee, United States

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Arlington, Texas, United States

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Carrollton, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Temple, Texas, United States

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Salt Lake City, Utah, United States

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Burlington, Vermont, United States

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Multiple Cities, Australia

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Multiple Cities, Brazil

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Multiple Cities, Bulgaria

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Multiple Cities, Chile

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Multiple Cities, Croatia

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Multiple Cities, Estonia

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Multiple Cities, Guatemala

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Related Publications (1)

• DeFronzo RA, Burant CF, Fleck P, Wilson C, Mekki Q, Pratley RE. Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin-treated patients with type 2 diabetes. J Clin Endocrinol Metab. 2012 May;97(5):1615-22. doi: 10.1210/jc.2011-2243. Epub 2012 Mar 14.

  PMID: 22419732 RESULT

Related Links

• ACTOS® Package Insert

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Glucose Intolerance; Hyperglycemia

Interventions

alogliptin; Pioglitazone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Sr. VP, Clinical Science
• Organization: Takeda Global Research and Development Center, Inc.

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• VP Biological Sciences

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2006
• First Posted: May 22, 2006
• Study Start: May 1, 2006
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: April 4, 2013
• Results First Posted: April 4, 2013

Record last verified: 2013-02

Locations

AU (1); BU (1); CR (1); NZ (1); US (72); LA (1); BR (1); IN (1); PE (1); RO (1); RU (1); GU (1); ES (1); ZA (1); UA (1); IL (1); CL (1); ME (1); SE (1)