Efficacy of Pioglitazone and Fortamet Combination Therapy in Subjects With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00754403
First received: September 17, 2008
Last updated: July 1, 2010
Last verified: July 2010
  Purpose

The purpose of this study is to determine the efficacy of pioglitazone and metformin combination therapy, once daily (QD), on glycosylated hemoglobin in adults with type 2 diabetes.


Condition Intervention Phase
Diabetes Mellitus
Drug: Pioglitazone and metformin
Drug: Metformin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Effects on Glycemic Control With Concomitantly Administered Pioglitazone HCl and Metformin HCl Extended Release (Fortamet®) in Subjects With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Takeda:

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

Secondary Outcome Measures:
  • Change from randomization in Fasting Plasma Glucose [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in Insulin [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in Pro-Insulin [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in Homeostasis Model Assessment [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in Triglycerides [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in Total Cholesterol [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in Low-Density Lipoprotein Cholesterol [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in high-density Lipoprotein Cholesterol [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in Lipid Fractionation [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in High Sensitivity C-Reactive Protein [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in Creatine Phosphokinase [ Time Frame: Final Visit ] [ Designated as safety issue: No ]
  • Change from randomization in Creatine Phosphokinase [ Time Frame: Final Visit ] [ Designated as safety issue: Yes ]

Enrollment: 312
Study Start Date: July 2005
Study Completion Date: October 2006
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pioglitazone 30 mg QD + Metformin 1000 mg QD Drug: Pioglitazone and metformin
Pioglitazone 30 mg, tablets, orally, once daily and metformin 1000 mg, tablets, orally once daily for up to 16 weeks.
Other Names:
  • Actos
  • AD-4833XT
  • Fortamet
Active Comparator: Metformin 1000 mg QD Drug: Metformin
Pioglitazone placebo-matching tablets, orally, once daily and metformin 1000 mg, tablets, orally once daily for up to 16 weeks.
Other Name: Fortamet

Detailed Description:

Pioglitazone (ACTOS®) is a member of a class of oral antidiabetic agents known as thiazolidinediones. The insulin-sensitizing actions of thiazolidinediones are at least partially mediated through the peroxisome proliferator-activated receptor gamma. These receptors are found primarily in adipocytes, vascular endothelial cells, monocytes, hepatocytes, and to a lesser extent myocytes.

Metformin was developed as an extended-release formulation of metformin hydrochloride and designed for once-a-day oral administration. Metformin is an antihyperglycemic agent, which improves glucose tolerance in patients with, type 2 diabetes, lowering both basal and postprandial plasma glucose.

On 15 July 1999, the FDA approved pioglitazone for use as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. Pioglitazone is indicated for monotherapy and for use in combination with sulfonylureas, metformin, or insulin when diet and exercise plus the single agent do not result in adequate glycemic control. On 26 November 2003, the FDA approved the combined use of pioglitazone with metformin.

This study is designed to evaluate the effect on glycemic control when pioglitazone and metformin are taken together. Individuals participating in this study will provide written informed consent and will be required to commit to a screening visit and approximately 5 additional visits at the study center. Study participation is anticipated to be about 31 weeks (or approximately 8 months). Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations and electrocardiograms.

  Eligibility

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

Inclusion Criteria

  • 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
  • Diagnosed with type 2 diabetes and must have received appropriate counseling on lifestyle modification for type 2 diabetes including diet and exercise.
  • If taking metformin monotherapy or metformin and sulfonylurea combination therapy, has a glycosylated hemoglobin greater than or equal to 7.5% and less than or equal to 9.0% at screening and randomization.
  • If naïve or taking sulfonylurea monotherapy has an glycosylated hemoglobin greater than or equal to 8.5% and less than or equal to 10.0% at screening and greater than or equal to 7.5% and less than or equal to 9.0% at randomization.

Exclusion Criteria

  • Has type 1 diabetes mellitus
  • Currently taking any thiazolidinedione or have taken any thiazolidinedione within 12 weeks prior to screening
  • Has congestive heart failure; has a triglyceride level greater than 500 mg per dL
  • Diastolic blood pressure greater than 100 mmHg or a systolic pressure greater than 160 mmHg
  • Body mass index greater than or equal to 42 kg/m2 (weight /height2)
  • Alanine transaminase level greater than or equal to 2.5 times the upper limit of normal, active liver disease, or jaundice.
  • Male subjects who have a serum creatinine level greater than or equal to 1.5 mg per dL; female subjects who have a serum creatinine level greater than or equal to 1.4 mg per dL at the screening visit and at randomization.
  • Currently using insulin or has used insulin 3 months prior to Screening
  • Acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma.
  • Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

    • Chronically used oral or parenteral glucocorticoids (eg, prednisone, cortisone, hydrocortisone, dexamethasone)
    • Niacin greater than 200 mg per day, including niacin-containing products such as Advicor - 3 months prior to screening and during the study
    • Chronically used steroid-joint injections - 3 months prior to screening and during the study
    • Thiazolidinediones - 3 months prior to screening and during the study
    • Insulin - 3 months prior to screening
    • Other oral antidiabetic medications (eg, nateglinide [Starlix], acarbose [Precose]) with the exception of sulfonylurea - 3 months prior to screening and during the study
    • Metformin - Fortamet Stabilization and during the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00754403

Sponsors and Collaborators
Takeda
Investigators
Study Director: VP Clinical Science Strategy Takeda
  More Information

Additional Information:
No publications provided

Responsible Party: Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00754403     History of Changes
Other Study ID Numbers: 01-05-TL-OPIXT-010, U1111-1114-2423
Study First Received: September 17, 2008
Last Updated: July 1, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus, Lipoatrophic
Dyslipidemia
Drug Therapy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014