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

NCT00432276 | Completed Phase 3 Results

• 3 other identifiers: 01-06-TL-322OPI-0042006-006025-73U1111-1112-3363
• Study Type: interventional
• Target: 803
• Locations: 1 country
• Sites: 86

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.

Conditions

Diabetes Mellitus

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline and Weeks 26 and 52.

Secondary Outcomes (40)

• Change From Baseline in HbA1c Over Time

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

• Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5%

  Weeks 26 and 52.

• Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0%

  Weeks 26 and 52.

• Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5%

  Weeks 26 and 52.

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

  Weeks 26 and 52.

Study Arms (2)

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

EXPERIMENTAL

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; Drug: Pioglitazone; Drug: Metformin; Drug: Placebo

Pioglitazone 45 mg add-on to Metformin

ACTIVE COMPARATOR

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; Drug: Metformin; Drug: Placebo

Interventions

Alogliptin DRUG

Alogliptin tablets.

Also known as: SYR-322

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

Pioglitazone DRUG

Pioglitazone tablets.

Also known as: ACTOS®

Alogliptin 25 mg + Pioglitazone 30 mg add-on to Metformin; Pioglitazone 45 mg add-on to Metformin

Metformin DRUG

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

Alogliptin 25 mg + Pioglitazone 30 mg add-on to Metformin; Pioglitazone 45 mg add-on to Metformin

Placebo DRUG

Matching placebo tablets.

Alogliptin 25 mg + Pioglitazone 30 mg add-on to Metformin; Pioglitazone 45 mg add-on to Metformin

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (86)

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Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Lake Havasu City, Arizona, United States

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Little Rock, Arkansas, United States

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Foothill Ranch, California, United States

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Los Alamitos, California, United States

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Los Angeles, California, United States

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Pismo Beach, California, United States

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San Diego, California, United States

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Golden, Colorado, United States

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Clearwater, Florida, United States

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Hialeah, Florida, United States

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Lakeland, Florida, United States

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Marianna, Florida, United States

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Miami, Florida, United States

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North Miami Beach, Florida, United States

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Pembroke Pines, Florida, United States

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Sebastian, Florida, United States

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South Miami, Florida, United States

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Tampa, Florida, United States

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Winter Park, Florida, United States

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Blue Ridge, Georgia, United States

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Conyers, Georgia, United States

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Decatur, Georgia, United States

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Duluth, Georgia, United States

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Dunwoody, Georgia, United States

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Warner Robins, Georgia, United States

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Boise, Idaho, United States

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Coeur d'Alene, Idaho, United States

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Burr Ridge, Illinois, United States

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Chicago, Illinois, United States

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Melrose Park, Illinois, United States

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Naperville, Illinois, United States

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O'Fallon, Illinois, United States

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Bloomington, Indiana, United States

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Mishawaka, Indiana, United States

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Overland Park, Kansas, United States

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Marrero, Louisiana, United States

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Elkton, Maryland, United States

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Rockville, Maryland, United States

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Towson, Maryland, United States

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Marlborough, Massachusetts, United States

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Bay City, Michigan, United States

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Saint Clair Shores, Michigan, United States

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McCook, Nebraska, United States

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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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West Caldwell, New Jersey, United States

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Asheboro, North Carolina, United States

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Charlotte, North Carolina, United States

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Mooresville, North Carolina, United States

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Shelby, North Carolina, United States

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Sparta, North Carolina, United States

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Bismarck, North Dakota, United States

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Orrville, Ohio, United States

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Norman, Oklahoma, United States

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Ashland, Oregon, United States

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Aliquippa, Pennsylvania, United States

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Altoona, Pennsylvania, United States

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Dawningtown, Pennsylvania, United States

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Fleetwood, Pennsylvania, United States

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Kingston, Pennsylvania, United States

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Norristown, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Tipton, Pennsylvania, United States

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Florence, South Carolina, United States

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Taylors, South Carolina, United States

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Williamston, South Carolina, United States

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Watertown, South Dakota, United States

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Kingsport, Tennessee, United States

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Milan, Tennessee, United States

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Nashville, Tennessee, United States

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Arlington, Texas, United States

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Austin, Texas, United States

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Colleyville, Texas, United States

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El Paso, Texas, United States

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Garland, Texas, United States

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Houston, Texas, United States

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Hurst, Texas, United States

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San Antonio, Texas, United States

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Seguin, Texas, United States

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Hampton, Virginia, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Virginia Beach, Virginia, United States

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Related Publications (1)

• 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.

  PMID: 21733058 RESULT

Related Links

• ACTOS® Package Insert

MeSH Terms

Conditions

Diabetes Mellitus; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus, Lipoatrophic; Dyslipidemias; Hyperglycemia

Interventions

alogliptin; Pioglitazone; Metformin

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

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

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2007
• First Posted: February 7, 2007
• Study Start: January 1, 2007
• Primary Completion: May 1, 2009
• Study Completion: June 1, 2009
• Last Updated: April 4, 2013
• Results First Posted: April 4, 2013

Record last verified: 2013-04

Locations

US (86)