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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 Glucose

Change 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

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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

Page last updated: August 23, 2015

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