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Efficacy and Safety of Pioglitazone and Metformin Combination Therapy in Treating Type 2 Diabetes Mellitus.
This study has been completed.
Sponsored by: Takeda Global Research & Development Center, Inc.
Information provided by: Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00727857
  Purpose

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


Condition Intervention Phase
Diabetes Mellitus
Drug: Pioglitazone and metformin
Drug: Pioglitazone
Drug: Metformin
Phase III

MedlinePlus related topics: Diabetes
Drug Information available for: Pioglitazone Pioglitazone hydrochloride Metformin Metformin hydrochloride Dextrose
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase 3b, Double-Blind, Randomized Study to Determine the Efficacy and Safety of Pioglitazone HCl and Metformin HCl Fixed-Dose Combination Therapy Compared to Pioglitazone HCl Monotherapy and to Metformin HCl Monotherapy in the Treatment of Subjects With Type 2 Diabetes

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:
  • Change from Baseline in Glycosylated Hemoglobin [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Fasting Plasma Glucose [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Fasting Insulin [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Homeostasis Model Assessment [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in High Sensitivity C-reactive Protein [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Adiponectin [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Total Cholesterol [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Low-Density Lipoprotein cholesterol [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in High-Density Lipoprotein cholesterol [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Triglycerides [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Lipid Fractionation [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]

Enrollment: 600
Study Start Date: June 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental Drug: Pioglitazone and metformin
Pioglitazone 15 mg /metformin 850 mg combination, tablets, orally, twice daily for up to 24 weeks.
2: Active Comparator Drug: Pioglitazone
Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks.
3: Active Comparator Drug: Metformin
Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Detailed Description:

Pioglitazone hydrochloride (ACTOS®) is a member of a class of oral antidiabetic agents known as thiazolidinediones, which act by reducing insulin resistance. Insulin resistance is a key feature of dysmetabolic syndrome and has been suggested to be the common pathophysiologic basis of both atherosclerosis and type 2 diabetes. Pioglitazone binds to peroxisome proliferator-activated receptors, an effect that is associated with altered transcription of genes capable of influencing carbohydrate and lipid metabolism.

Metformin hydrochloride is an oral antihyperglycemic drug not chemically or pharmacologically related to thiazolidinediones. Metformin is a biguanide, which has been shown to be effective in improving glycemic control in diabetic patients. Metformin inhibits hepatic glucose production, most likely through an inhibition of gluconeogenesis, and its use is associated with an improvement in tissue sensitivity to insulin. In accordance with published algorithms for the use of combination therapy for the treatment of type 2 diabetes, physicians have traditionally combined metformin with other antidiabetic agents.

This study will determine the effect of a fixed-dose combination of metformin with pioglitazone, compared to metformin monotherapy and pioglitazone monotherapy.

Study participation is anticipated to be approximately 6.5 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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
    • Chronically used oral or parenteral glucocorticoids
    • Niacin greater than 200 mg per day, including niacin-containing products such as Advicor
    • Chronically used steroid-joint injections
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00727857

  Show 77 Study Locations
Sponsors and Collaborators
Takeda Global Research & Development Center, Inc.
Investigators
Study Director: VP Clinical Science Strategy Takeda Global Research & Development Center, Inc.
  More Information

ACTOPLUS MET® Package Insert  This link exits the ClinicalTrials.gov site
FDA Safety Alerts and Recalls  This link exits the ClinicalTrials.gov site

Responsible Party: Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers: 01-06-TL-OPIMET-008
Study First Received: July 30, 2008
Last Updated: January 13, 2009
ClinicalTrials.gov Identifier: NCT00727857  
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:
Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus, Lipoatrophic
Dyslipidemia
Drug Therapy

Study placed in the following topic categories:
Metabolic Diseases
Pioglitazone
Metformin
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Dyslipidemias

Additional relevant MeSH terms:
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009