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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00521742
• Date of registration: 25/08/2007
• Prospective Registration: No
• Primary sponsor: Takeda
• Public title: Efficacy of Pioglitazone Compared to Glyburide in Treating Subjects With Type 2 Diabetes Mellitus and Mild Cardiac Disease
• Scientific 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)
• Date of first enrolment: March 2001
• Target sample size: 300
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00521742
• 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
• Phase: Phase 3

Contacts

• Name: VP Clinical Science Strategy
• Affiliation: Takeda Global Research and Developmnet Center Inc

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 79 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Diabetes Mellitus

Intervention(s)

Drug: Pioglitazone

Drug: Glyburide

Primary Outcome(s)

Change in the walking distance during a standardized 6-minute walk test. [Time Frame: Weeks 2, 16, 24, 40, and 52 or Final Visit]

Secondary Outcome(s)

Change in Heart Rate [Time Frame: Weeks 24 and 52 or Final Visit]

Change from Baseline in Electrocardiogram Parameter (Cardiac Index) [Time Frame: Week 52 or Final Visit]

Change from Baseline in Electrocardiogram Parameter (Fractional Shortening) [Time Frame: Week 52 or Final Visit]

Change from Baseline in Electrocardiogram Parameter (Left Ventricular Ejection Fraction) [Time Frame: Week 52 or Final Visit]

Change from Baseline in 12-lead Electrocardiogram Parameter (Ventricular Heart Rate) [Time Frame: Weeks 24 and 52 or Final Visit]

Change in Body Weight [Time Frame: Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit]

Change from Baseline in Electrocardiogram Parameter (Left Ventricular Mass) [Time Frame: Week 52 or Final Visit]

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]

Change in Blood Pressure [Time Frame: Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit]

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]

Secondary ID(s)

01-00-TL-OPI-520

U1111-1114-1616

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Takeda Pharmaceuticals North America, Inc.