Efficacy of Pioglitazone Compared to Glyburide in Treating Subjects With Type 2 Diabetes Mellitus and Mild Cardiac Disease

This study has been completed.
Sponsor:
Collaborator:
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00521742
First received: August 25, 2007
Last updated: February 27, 2012
Last verified: February 2012
  Purpose

The purpose of this study is to evaluate the cardiovascular effects of pioglitazone, once daily (QD), versus glyburide when administered to patients with type 2 diabetes mellitus and mild cardiac disease.


Condition Intervention Phase
Diabetes Mellitus
Drug: Pioglitazone
Drug: Glyburide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Comparator-Controlled Study of Pioglitazone HCl vs Glyburide in the Treatment of Patients With Type 2 (Non-Insulin-Dependent) Diabetes Mellitus and Mild Cardiac Disease (NYHA I)

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change in the walking distance during a standardized 6-minute walk test. [ Time Frame: Weeks 2, 16, 24, 40, and 52 or Final Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Morbidity and Mortality Due to Cardiovascular Events. [ Time Frame: At occurrence or Weeks 2, 4, 6, 8, 12, 16, 24, 32, 36, 40, 48, and 52 or Final Visit ] [ Designated as safety issue: No ]
  • Change in Cardiovascular Treatment Program. [ Time Frame: At occurrence or Weeks 2, 4, 6, 8, 12, 16, 24, 32, 36, 40, 48, and 52 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in 12-lead Electrocardiogram Parameter (Ventricular Heart Rate) [ Time Frame: Weeks 24 and 52 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Electrocardiogram Parameter (Left Ventricular Mass) [ Time Frame: Week 52 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Electrocardiogram Parameter (Left Ventricular Ejection Fraction) [ Time Frame: Week 52 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Electrocardiogram Parameter (Cardiac Index) [ Time Frame: Week 52 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Electrocardiogram Parameter (Fractional Shortening) [ Time Frame: Week 52 or Final Visit ] [ Designated as safety issue: No ]
  • Change in Blood Pressure [ Time Frame: Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit ] [ Designated as safety issue: No ]
  • Change in Heart Rate [ Time Frame: Weeks 24 and 52 or Final Visit ] [ Designated as safety issue: No ]
  • Change in Body Weight [ Time Frame: Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit ] [ Designated as safety issue: No ]

Enrollment: 300
Study Start Date: March 2001
Study Completion Date: January 2003
Primary Completion Date: January 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pioglitazone 15 mg to 45 mg QD Drug: Pioglitazone
Pioglitazone 15 mg to 45 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally, once daily for up to 52 weeks.
Other Names:
  • Actos
  • AD4833
Active Comparator: Glyburide 2.5 mg to 15 mg, QD Drug: Glyburide
Glyburide 2.5 mg to 15 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 52 weeks.
Experimental: Pioglitazone 15 mg or 30 mg QD Drug: Pioglitazone
Pioglitazone 15 mg or 30 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally once daily for up to 52 weeks.
Other Names:
  • Actos
  • AD4833
Active Comparator: Glyburide 5 mg or 10 mg, QD Drug: Glyburide
Glyburide 5 mg or 10 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally once daily for up to 52 weeks.

Detailed Description:

Diabetes is a chronic disease involving multiple metabolic defects that include inadequate insulin activity and resultant hyperglycemia. Individuals' differing genetic predisposition, level of physical activity, and age all contribute to variations in the onset and severity of type 2 diabetes. However, progression of this disease typically follows a characteristic pattern that begins as a reduced sensitivity of hepatic and peripheral-tissues to circulating insulin (ie, insulin resistance). The body's decreasing ability to produce adequate insulin to overcome insulin resistance (ie, insulin deficiency due to beta-cell insufficiency) results in impaired glucose tolerance and ultimately overt diabetes. In the United States, an estimated 17 million people have diabetes, with type 2 diabetes occurring in approximately 90% to 95% of cases.

The goal of treating type 2 diabetes is to control blood glucose and thereby prevent long-term complications. Adequate glycemic control is paramount in attempting to avert chronic complications, including blindness, renal dysfunction and resultant dialysis or renal transplantation, neuropathy, and nontraumatic amputations. Intensive glucose management in the early stages of diabetes may help forestall complications.

Pioglitazone is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. Glyburide, is an oral antidiabetic agent of the sulfonylurea class. The primary purpose of this study is to evaluate the cardiovascular effects of pioglitazone versus glyburide when administered to patients with type 2 diabetes mellitus and mild cardiac disease

Study participation is anticipated to be approximately 1 year and 2 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
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 mellitus.
  • Naive to oral antidiabetic pharmacologic therapy, who were currently taking sulfonylurea monotherapy, who were currently taking sulfonylurea/metformin combination therapy, or who were currently taking metformin monotherapy.
  • Mild cardiac disease New York Heart Association functional Class I.
  • Participated in dietary counseling.
  • Glycosylated hemoglobin greater than or equal to 7.5% and less than 12% at Screening if naïve to oral antidiabetic pharmacologic therapy or taking metformin monotherapy, or greater than or equal to 6.5% and less than 12% if currently taking sulfonylurea monotherapy or taking ulfonylurea/metformin combination therapy.
  • Stable therapy for cardiovascular dysfunction, defined as no change in therapy for greater than or equal to 4 weeks prior to Randomization.

Exclusion Criteria:

  • Within the past 30 days treated with rosiglitazone, pioglitazone, or troglitazone or those previously treated with rosiglitazone, pioglitazone, or troglitazone but discontinued from therapy because of lack of efficacy or clinical or laboratory signs of intolerance.
  • Treated with a sulfonylurea but discontinued for lack of efficacy or clinical or laboratory intolerance.
  • Currently taking insulin or on continuous insulin therapy for control of their diabetes
  • Type 1 (insulin-dependent) diabetes mellitus or a history of ketoacidosis.
  • Any other investigational drug during the 30 days prior to Visit 1 or who will receive such a drug during the time-frame of this study.
  • History of chronic alcoholism or drug abuse during the 6 months prior to the study.
  • New York Heart Association functional Class II, III, or IV cardiac disease at Screening, or previous history of Class III or IV.
  • Any of the following:

    • myocardial infarction
    • coronary angioplasty or bypass graft
    • unstable angina pectoris
    • transient ischemic attacks
    • documented cerebrovascular accident. 9. Abdominal, thoracic, or vascular surgery during the 3 months prior to Visit 1.
  • Planned surgical or catheterization intervention within 6 months following Visit 1.
  • Awaiting cardiac transplantation.
  • Intercurrent illness severe enough to require hospitalization during the 3 weeks prior to Visit 1.
  • Body mass index greater than 48 kg/m2 as calculated by [weight (kg)/height (m)2].
  • Anemia having hemoglobin less than 10.5 g per dL for men and 10.0 g per dL for women.
  • Triglyceride level greater than 500 mg per dL.
  • Clinical evidence of active liver disease or alanine transaminase levels greater than 2.5 times the upper limit of normal.
  • Serum creatinine greater than 2.0 mg per dL for men and 1.8 mg per dL for women or urinalysis protein (albumin) excretion levels greater than 2 plus on Combistix or equivalent and on repeat 24-hour results with greater than 3 g macroproteinuria.
  • Unstable coronary syndromes.
  • Systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 90 mm Hg at Screening.
  • Serious uncontrolled cardiac rhythm disturbances.
  • Symptomatic orthostatic hypotension or systolic blood pressure less than 90 mm Hg.
  • Severe, advanced peripheral vascular disease (limb-threatening ischemia) or claudication resulting in the inability to walk greater than 1 block or to climb 10 stairs without interruption.
  • Lower extremity amputation that would prevent the patient from performing the exercise test.
  • Any other serious disease or condition which might affect life-expectancy or make it difficult to successfully manage and follow the subjects according to the protocol.
  • Unexplained clinically significant findings on chest x-ray.
  • 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:

    • Oral, injected, or inhaled corticosteroids of greater than 2 week duration, or the need for recurrent us of corticosteroids.
    • Prescription niacin
    • Anti-diabetic medications except metformin
    • Cardiovascular medications must remain stable for at least 4 weeks prior to Randomization
    • Non-steroidal anti-inflammatory drugs
    • Aspirin greater than 325 mg per day
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00521742

Sponsors and Collaborators
Takeda
Takeda Pharmaceuticals North America, Inc.
Investigators
Study Director: VP Clinical Science Strategy Takeda Global Research and Developmnet Center Inc
  More Information

Additional Information:
Publications:
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00521742     History of Changes
Other Study ID Numbers: 01-00-TL-OPI-520, U1111-1114-1616
Study First Received: August 25, 2007
Last Updated: February 27, 2012
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
Heart Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Cardiovascular Diseases
Pioglitazone
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014