Efficacy and Safety of Pioglitazone and Metformin Combination Therapy in Treating Type 2 Diabetes Mellitus.
Information source: Takeda
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes Mellitus
Intervention: Pioglitazone and metformin (Drug); Pioglitazone (Drug); Metformin (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Takeda Official(s) and/or principal investigator(s): VP Clinical Science Strategy, Study Director, Affiliation: Takeda
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Percent Change From Baseline in Glycosylated Hemoglobin
Secondary outcome: Change From Baseline in Fasting Plasma GlucoseChange From Baseline in Fasting Insulin Change From Baseline in Homeostasis Model Assessment - Insulin Resistance Median Percent Change From Baseline in High Sensitivity C-reactive Protein Change From Baseline in Adiponectin Change From Baseline in Total Cholesterol Change From Baseline in Low-Density Lipoprotein Cholesterol Change From Baseline in High-Density Lipoprotein Cholesterol Change From Baseline in Triglycerides Change From Baseline in Mean Low Density Lipoprotein Particle Concentration Change From Baseline in Mean Low Density Lipoprotein Particle Size Change From Baseline in Large Low Density Lipoprotein (L3) Concentration Change From Baseline in Intermediate-Density Low Density Lipoprotein Concentration Change From Baseline in Medium-Small Low Density Lipoprotein Concentration Change From Baseline in Small Low Density Lipoprotein Concentration Change From Baseline in Very Small Low Density Lipoprotein Concentration Change From Baseline in Mean High Density Lipoprotein Particle Concentration Change From Baseline in Mean High Density Lipoprotein Particle Size Change From Baseline in Large High Density Lipoprotein (H4+H5) Concentration Change From Baseline in Intermediate-Medium High Density Lipoprotein (H3) Concentration Change From Baseline in Small High Density Lipoprotein (H1+H2) Concentration Change From Baseline in Mean Very Low Density Lipoprotein Particle Concentration Change From Baseline in Mean Very Low Density Lipoprotein Particle Size Change From Baseline in Large-Chylomicrons Very Low Density Lipoprotein Concentration Change From Baseline in Medium-Intermediate Very Low Density Lipoprotein (V3+V4) Concentration Change From Baseline in Small Very Low Density Lipoprotein (V1+V2) Concentration
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Providencia-Santiago, Chile
Temuco, Chile
Aibonito, Puerto Rico
Caguas, Puerto Rico
Ciales, Puerto Rico
Coto Laurel, Puerto Rico
Guayma, Puerto Rico
Guaynabo, Puerto Rico
Rio Piedras, Puerto Rico
Birmingham, Alabama, United States
Haleyville, Alabama, United States
Montgomery, Alabama, United States
Pell City, Alabama, United States
Phoenix, Arizona, United States
Tucson, Arizona, United States
Anaheim, California, United States
Artesia, California, United States
Dinuba, California, United States
Long Beach, California, United States
Los Angeles,, California, United States
Norwalk, California, United States
Orange, California, United States
Santa Ana, California, United States
Santa Monica, California, United States
Pueblo, Colorado, United States
Altamonte Springs, Florida, United States
Coral Gables, Florida, United States
Hialeah, Florida, United States
Miami,, Florida, United States
Panama City, Florida, United States
Plantation, Florida, United States
St Petersburg, Florida, United States
St. Cloud, Florida, United States
Tampa, Florida, United States
Columbus, Georgia, United States
Boise, Idaho, United States
Coeur d' Alene,, Idaho, United States
Chicago, Illinois, United States
Flossmoor, Illinois, United States
Peoria, Illinois, United States
Elkhart, Indiana, United States
Zapopan, Jalisco, Mexico
Shawnee,, Kansas, United States
Southfield, Michigan, United States
Chesterfield, Missouri, United States
Billings, Montana, United States
Elizabeth, New Jersey, United States
Fayetteville, New York, United States
New York, New York, United States
Durham, North Carolina, United States
Pinehurst, North Carolina, United States
Monterrey, Nuevo Leon, Mexico
Cincinnati, Ohio, United States
Perrysburg, Ohio, United States
Zanesville, Ohio, United States
Oklahoma City, Oklahoma, United States
Eugene, Oregon, United States
Fleetwood, Pennsylvania, United States
Norristown, Pennsylvania, United States
Cranston, Rhode Island, United States
Simpsonville,, South Carolina, United States
Varnville, South Carolina, United States
Fayetteville, Tennessee, United States
Corpus Christi, Texas, United States
Dallas, Texas, United States
El Paso, Texas, United States
Houston, Texas, United States
McAllen, Texas, United States
Mission, Texas, United States
New Braunfels, Texas, United States
North Richland Hills, Texas, United States
San Antonio,, Texas, United States
Bountiful, Utah, United States
Salt Lake City, Utah, United States
Petersburg, Virginia, United States
Port Orchard, Washington, United States
Spokane, Washington, United States
Additional Information
ACTOPLUS MET® Package Insert FDA Safety Alerts and Recalls
Related publications: 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.
Starting date: June 2007
Last updated: July 27, 2011
|