Efficacy and Safety of Pioglitazone and Metformin Combination Therapy in Treating Type 2 Diabetes Mellitus.

NCT00727857 | Completed Phase 3 Results

• 2 other identifiers: 01-06-TL-OPIMET-008U1111-1114-0371
• Study Type: interventional
• Target: 600
• Locations: 4 countries
• Sites: 77

Brief Summary

The purpose of this study is to determine the efficacy of pioglitazone, twice daily (BID), combined with metformin versus pioglitazone taken alone and metformin taken alone in treating Type 2 Diabetes Mellitus.

Conditions

Diabetes Mellitus

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Glycosylated Hemoglobin

  The change between the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at final visit or week 24 and Glycosylated Hemoglobin collected at baseline.

  Baseline and Week 24

Secondary Outcomes (26)

• Change From Baseline in Fasting Plasma Glucose

  Baseline and Week 24

• Change From Baseline in Fasting Insulin

  Baseline and Week 24

• Change From Baseline in Homeostasis Model Assessment - Insulin Resistance

  Baseline and Week 24

• Median Percent Change From Baseline in High Sensitivity C-reactive Protein

  Baseline and Week 24

• Change From Baseline in Adiponectin

  Baseline and Week 24

Study Arms (3)

Pioglitazone 15 mg /Metformin 850 mg BID

EXPERIMENTAL

Drug: Pioglitazone and metformin

Pioglitazone 15 mg BID

ACTIVE COMPARATOR

Drug: Pioglitazone

Metformin 850 mg BID

ACTIVE COMPARATOR

Drug: Metformin

Interventions

Pioglitazone and metformin DRUG

Pioglitazone 15 mg /metformin 850 mg combination, tablets, orally, twice daily for up to 24 weeks.

Also known as: ACTOPLUS MET

Pioglitazone 15 mg /Metformin 850 mg BID

Pioglitazone DRUG

Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks.

Also known as: ACTOS®, AD4833

Pioglitazone 15 mg BID

Metformin DRUG

Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Also known as: Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet

Metformin 850 mg BID

Eligibility Criteria

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

You may qualify if:

• Has type 2 diabetes.
• Has received no treatment with antidiabetic medication in the 12 weeks prior to Screening, other than short-term use defined as less than or equal to 15 days.
• A glycosylated hemoglobin greater than or equal to 7.5% and less than or equal to 10.0% at Screening.
• Body mass index less than or equal to 45 kg/m2.
• Has received counseling on lifestyle modification for type 2 diabetes, including diet and exercise.
• 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.
• Stable condition as determined by a physician.

You may not qualify if:

• Type 1 diabetes.
• Unstable angina or heart failure of any etiology with New York Heart Association functional class III or IV.
• History of myocardial infarction, cerebrovascular accident, percutaneous coronary intervention, coronary artery bypass graft, or transient ischemic attack in the 6 months prior to Screening.
• Male participant has a serum creatinine level greater than or equal to 1.5 mg per dL or female subject has a serum creatinine level greater than or equal to 1.4 mg per dL.
• Has a triglyceride level greater than 500 mg per dL.
• Male participant has a hemoglobin level less than 10.5 g per dL or female subject has a hemoglobin level less than 10.0 g per dL.
• Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
• History of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day) within 2 years prior to Screening.
• Has been discontinued from a thiazolidinedione or metformin therapy due to lack of efficacy or clinical or laboratory signs of intolerance.
• Previous history of cancer, other than basal cell or stage 1 squamous cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study medication.
• History of acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma.
• Any disease or condition at Screening or Randomization that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol.
• Currently participating in another investigational study or has participated in an investigational study within 30 days prior to randomization.
• Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
• Antidiabetic medications other than study medication

Sponsors & Collaborators

• Takeda: lead

Study Sites (77)

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Birmingham, Alabama, United States

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Haleyville, Alabama, United States

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Montgomery, Alabama, United States

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Pell City, Alabama, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Anaheim, California, United States

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Artesia, California, United States

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Dinuba, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Norwalk, California, United States

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Orange, California, United States

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Santa Ana, California, United States

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Santa Monica, California, United States

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Pueblo, Colorado, United States

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Altamonte Springs, Florida, United States

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Coral Gables, Florida, United States

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Hialeah, Florida, United States

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Miami, Florida, United States

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Panama City, Florida, United States

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Plantation, Florida, United States

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Saint Cloud, Florida, United States

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St. Petersburg, Florida, United States

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Tampa, Florida, United States

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Columbus, 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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Chicago, Illinois, United States

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Flossmoor, Illinois, United States

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Peoria, Illinois, United States

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Elkhart, Indiana, United States

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Shawnee, Kansas, United States

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Southfield, Michigan, United States

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Chesterfield, Missouri, United States

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Billings, Montana, United States

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Elizabeth, New Jersey, United States

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Fayetteville, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Pinehurst, North Carolina, United States

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Cincinnati, Ohio, United States

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Perrysburg, Ohio, United States

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Zanesville, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Eugene, Oregon, United States

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Fleetwood, Pennsylvania, United States

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Norristown, Pennsylvania, United States

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Cranston, Rhode Island, United States

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Simpsonville, South Carolina, United States

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Varnville, South Carolina, United States

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Fayetteville, Tennessee, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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El Paso, Texas, United States

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Houston, Texas, United States

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McAllen, Texas, United States

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Mission, Texas, United States

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New Braunfels, Texas, United States

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North Richland Hills, Texas, United States

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San Antonio, Texas, United States

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Bountiful, Utah, United States

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Salt Lake City, Utah, United States

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Petersburg, Virginia, United States

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Port Orchard, Washington, United States

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Spokane, Washington, United States

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Providencia-Santiago, Chile

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Temuco, Chile

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Zapopan, Jalisco, Mexico

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Monterrey, Nuevo León, Mexico

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Aibonito, Puerto Rico

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Caguas, Puerto Rico

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Ciales, Puerto Rico

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Coto Laurel, Puerto Rico

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Guayma, Puerto Rico

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Guaynabo, Puerto Rico

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Rio Piedras, Puerto Rico

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Related Publications (2)

• Perez A, Zhao Z, Jacks R, Spanheimer R. Efficacy and safety of pioglitazone/metformin fixed-dose combination therapy compared with pioglitazone and metformin monotherapy in treating patients with T2DM. Curr Med Res Opin. 2009 Dec;25(12):2915-23. doi: 10.1185/03007990903350011.

  PMID: 19827910 BACKGROUND

• Perez A, Jacks R, Arora V, Spanheimer R. Effects of pioglitazone and metformin fixed-dose combination therapy on cardiovascular risk markers of inflammation and lipid profile compared with pioglitazone and metformin monotherapy in patients with type 2 diabetes. J Clin Hypertens (Greenwich). 2010 Dec;12(12):973-82. doi: 10.1111/j.1751-7176.2010.00389.x. Epub 2010 Nov 8.

  PMID: 21122063 RESULT

Related Links

• ACTOPLUS MET® Package Insert

MeSH Terms

Conditions

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

Interventions

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 Clinical Science Strategy

  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

Study Record Dates

• First Submitted: July 30, 2008
• First Posted: August 4, 2008
• Study Start: June 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: July 29, 2011
• Results First Posted: March 9, 2010

Record last verified: 2011-07

Locations

US (66); ME (2); PR (7); CL (2)