Efficacy Study of Pioglitazone Compared to Glimepiride on Coronary Atherosclerotic Disease Progression in Subjects With Type 2 Diabetes Mellitus

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00225277
• Date of registration: 21/09/2005
• Prospective Registration: No
• Primary sponsor: Takeda
• Public title: Efficacy Study of Pioglitazone Compared to Glimepiride on Coronary Atherosclerotic Disease Progression in Subjects With Type 2 Diabetes Mellitus PERISCOPE
• Scientific title: A Double-Blind, Randomized, Comparator-Controlled Study In Subjects With Type 2 Diabetes Mellitus Comparing the Effects of Pioglitazone HCl Versus Glimepiride on the Rate of Progression of Coronary Atherosclerotic Disease as Measured by Intravascular Ultrasound
• Date of first enrolment: July 2003
• Target sample size: 547
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00225277
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

Argentina, Canada, Chile, United States

Contacts

• Name: VP Clinical Science
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

- Females of childbearing potential who were sexually active agreed to use adequate
contraception, and can neither be pregnant nor lactating from Screening throughout the
duration of the study.

- Had a diagnosis of type 2 diabetes mellitus

- Have received appropriate counseling on lifestyle modification for type 2 diabetes,
including diet and exercise.

- naïve to or was not currently taking antidiabetic therapy, or were currently treated
with monotherapy or combination therapy.

- Had a glycosylated hemoglobin level greater than or equal to 6.0% and less than 9% at
screening if taking antidiabetic medication or greater than or equal to 6.5% and less
than 10% at screening if naive to or not taking antidiabetic medication.

- Angiographic criteria:

- Entire Coronary Circulation: must have angiographic evidence of coronary heart
disease as defined by at least 1 lesion in a native coronary artery that has
greater than or equal to 20% reduction in lumen diameter by angiographic visual
estimation.

- Left Main Coronary Artery: must not have greater than 50% reduction in lumen
diameter by visual angiographic estimation.

- Target Coronary Artery:

- The target vessel, which includes the main artery and all of its side
branches, had not undergone prior percutaneous coronary intervention or
coronary artery bypass graft surgery.

- The target vessel, which includes the main artery and all of its side
branches, was not currently a candidate for intervention or a likely
candidate for intervention over the next 72 weeks.

- The target vessel was not a bypass graft.

- The target vessel was not infarct related.

- Had previous coronary artery bypass surgery at least six weeks prior to the qualifying
intravascular ultrasound are eligible provided they are stable and meet all other
entry criteria.

- Had an intravascular ultrasound tape deemed to be of acceptable intravascular
ultrasound image quality and demonstrated adherence to the intravascular ultrasound
interrogation protocol, as determined by the intravascular ultrasound Core Laboratory™
assessment.

Exclusion Criteria:

- Had type I diabetes mellitus.

- Had participated in another investigational study, or participated in an
investigational study 30 days prior to the start of this study, or who were scheduled
to participate in an investigational study during the time frame of this study.

- Male subjects who had a serum creatinine level greater than or equal to 2.0 mg/dL
(greater than or equal to 177 µmol/L) (greater than or equal to 1.5 mg/dL; [greater
than or equal to 133 µmol /L] if taking metformin) and female subjects who have serum
creatinine greater than or equal to 1.8 mg/dL [greater than or equal to 159 µmol /L]
(greater than or equal to 1.4 mg/dL [greater than or equal to 124 µmol /L] if taking
metformin).

- Had unexplained microscopic hematuria greater than +1, confirmed by repeat testing.

- Had a history of drug abuse or a history of alcohol abuse (defined as regular or daily
consumption of more than 4 alcoholic drinks per day) within the past 2 years.

- Had clinical cardiac failure as defined by New York Heart Association class III or IV,
or known left ventricular dysfunction measured as left ventricular ejection fraction
less than 40%, or by current use of diuretics or angiotensin converting enzyme
inhibitors for treatment of heart failure.

- Had an alanine transaminase level of greater than 2.5 times the upper limit of normal
active liver disease, or jaundice.

- Had a body mass index greater than 48 kg/m2 as calculated by weight (kg)/height (m2)
or weight (pounds)/height (inches) 2 x 703.

- Was required to take or intended to continue taking any disallowed medication, any
prescription medication, herbal treatment or over-the counter medication that may have
interfered with evaluation of the study medication, including:

- Chronically used oral glucocorticoids (eg, prednisone, cortisone, hydrocortisone,
dexamethasone)

- Niacin greater than100 mg a day, including niacin-containing products such as
Advicor®

- Chronically used steroid-joint injections

- Thiazolidinediones

- Sulfonylureas

- Metformin/sulfonylurea combination

- Other oral antidiabetic medications (eg, nateglinide [Starlix®], acarbose
[Precose®]) with the exception of metformin

- Had known or suspected malignancy or recurrence of malignancy within the past 5 years,
with the exception of basal cell carcinoma and Stage 1 squamous cell carcinoma of the
skin.

- Had any disease where, in the opinion of the investigator (or designee), survival is
expected to be less than 72 weeks.

- Clinical status was unstable (ie, requiring vasopressors or intravenous inotropes,
intra-aortic balloon pump, hypotension [systolic blood pressure less than 90 mm Hg]).

- Prior to the screening visit, was scheduled for a staged cardiac intervention
(percutaneous coronary intervention), peripheral vascular intervention, or coronary
artery bypass graft surgery following the screening angiography.

- In the opinion of the investigator (or designee) had clinically significant valvular
heart disease likely to require surgical repair/replacement during the course of the
study.

- Had persistent, uncontrolled hypertension (ie, sitting systolic blood pressure greater
than 160 mm Hg or sitting diastolic blood pressure greater than 100 mm Hg) at
randomization.

- Males who had hemoglobin less than 10.5 g/dL (less than 105 g/L) and female subjects
who had hemoglobin less than 10.0 g/dL (less than 100 g/L).

- Had a triglyceride level greater than 500 mg/dL (greater than 5.6 mmol/L).



Age minimum: 35 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diabetes Mellitus

Intervention(s)

Drug: Glimepiride

Drug: Pioglitazone

Primary Outcome(s)

Nominal Change From Baseline in Percent Atheroma Volume [Time Frame: Baseline and Final Visit (up to 72 weeks)]

Secondary Outcome(s)

Nominal Change From Baseline in Normalized Total Atheroma Volume [Time Frame: Baseline and Final Visit (up to 72 weeks)]

Number of Subjects Experiencing Any of the Composite Endpoint B Cardiovascular Events [Time Frame: Up to 72 weeks]

Number of Subjects Experiencing Any of the Composite Endpoint C Cardiovascular Events [Time Frame: Up to 72 weeks]

Number of Subjects Experiencing Any of the Composite Endpoint A Cardiovascular Events [Time Frame: Up to 72 weeks]

Secondary ID(s)

U1111-1114-0400

01-01-TL-OPI-516

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 10/06/2009
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00225277