Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Safety and Efficacy Study to Evaluate the Potential of Aleglitazar to Reduce Cardiovascular Risk in Coronary Heart Disease (CHD) Patients With a Recent Acute Coronary Syndrome (ACS) Event and Type 2 Diabetes Mellitus (T2D)
Brief Summary: This double-blind, parallel, two-arm study will evaluate the potential to reduce cardiovascular risk, the tolerability and long-term safety profile of aleglitazar compared to placebo on top of standard care in patients with recent acute coronary syndrome (ACS) and type 2 diabetes mellitus. Patients will be randomized to receive either aleglitazar or placebo once daily as oral doses. The study will last until at least 950 events occur, but time on study treatment will be for at least 2.5 years.


Options:
A: Inclusion Criteria

* Type 2 diabetes mellitus
* Glycosylated hemoglobin above the upper limit of normal (ie, the local equivalent of 6.5% for)
* Established history of macrovascular disease, defined as 1 or more of:

  * Myocardial infarction at least 6 months before entry into the study.
  * Stroke at least 6 months before entry into the study
  * Percutaneous coronary intervention or coronary artery bypass graft at least 6 months before entry into the study.
  * Acute coronary syndrome at least 3 months before entry into the study.
  * Objective evidence of coronary artery disease.
  * Peripheral arterial obstructive disease

Exclusion Criteria

* Signs of type 1 diabetes.
* Patients prescribed insulin as sole therapy for glycemic control of diabetes for 2 weeks or more at any time in the previous 3 months.
* Myocardial infarction, stroke, coronary artery bypass graft, or percutaneous cardiac intervention in the 6 months prior to enrolment.
* Acute coronary syndrome in the 3 months prior to enrolment.
* Heart failure at entry defined as patient having a New York Heart Association functional score of II or above.
* Had an appointment for a coronary angiogram or endovascular or surgical intervention.
* Leg ulcers, gangrene, or ischemic rest pain.
* Had an appointment for an angiogram or endovascular or surgical intervention for leg ischemia.
* Had undergone a major operation (defined as a surgical procedure lasting for more than 30 minutes) at any time in the previous 4 weeks.
* Significantly impaired hepatic function, defined as alanine aminotransferase greater than 2.5 times the upper limit of normal.
* Familial polyposis coli.
* Required dialysis.
* History of alcohol or drug abuse.
* Any other intercurrent disease believed to be likely to have a significant impact on the patient's life expectancy during the course of the study (eg, cancer).
* Patient was undergoing follow-up as part of another clinical trial or less than 3 months had elapsed since the last dose of an investigational drug or procedure.
* Hypersensitivity to pioglitazone or other TZD.
* Current use of pioglitazone or other TZD.
* Patient was known to be infected with human immunodeficiency virus or was known to have viral hepatitis.
* Women who were any of the following: pregnant, breast feeding, wished to become pregnant during the course of the study or of childbearing potential and not planning to use a reliable method of contraception throughout the study.
B: Inclusion Criteria:

* Adults \>18 years of age
* Type 2 diabetes mellitus
* Hospitalization for ACS event and randomization between hospital discharge and 8 weeks after the ACS index event (day of hospitalization)

Exclusion Criteria:

* Estimated glomerular filtration rate \<45 mL/min/1.73m2
* Concomitant treatment with a thiazolidinedione and/or fibrate
* Triglycerides \>400 mg/dL
* Anaemia
* Symptomatic congestive heart failure classified as New York Heart Association (NYHA) class II-IV (France and Germany: Symptomatic congestive heart failure classified as NYHA class I-IV)
C: Inclusion Criteria

1. Ages 40 years or greater at the time of randomization.
2. Ischemic stroke or TIA no less than 14 days and no more than 6 months before randomization
3. Documentation of insulin resistance as defined by a value over 3.0 on the Homeostasis Model Assessment of insulin sensitivity (HOMA).
4. Both ability and willingness to provide informed consent.
5. Presence of none of the exclusion criteria.

Exclusion Criteria

Permanent Exclusions

1. Severely disabling stroke as indicated by an inability to participate in scheduled follow-up activities.
2. Persons whose ischemic stroke or TIA was related to structural cardiac lesion, significant head trauma, proximal arterial dissection or medical instrumentation.
3. Diabetes mellitus as defined by recent use of medication for diabetes as an out-patient (\*see note below) or two fasting plasma blood sugars \> 126 mg/dL.
4. HgbA1c \> 7.0%.
5. Irreversible medical conditions likely to affect short-term survival or ability to participate in the study protocol. These include:

   * Cancer or other chronic disease with poor prognosis (predicted survival of less than four years).
   * Severe neurologic or psychiatric disease that would complicate the evaluation of study outcomes (e.g., dementia or schizophrenia).
6. History of intolerance to any thiazolidinedione.
7. Pregnancy or desire to become pregnant.
8. Oral contraceptive use.
9. Ongoing use of oral corticosteroids.
10. History of heart failure
11. Active liver disease as defined by known liver disease accompanied by cirrhosis, significant cholestasis, portal hypertension, hepatic encephalopathy, hepatic synthetic dysfunction, or expected significant loss of liver function over the course of the study.
12. History of bladder cancer.
13. Current participation in a conflicting clinical trial. A conflicting clinical trial is defined as a trial with any of following:

    * Intervention that is known to affect the incidence of stroke or myocardial infarction.
    * Intervention that is an experimental drug.
    * Outcome that includes stroke or myocardial infarction.
    * Exclusion for participation in another trial.

Temporary Exclusions Persons with temporary exclusions may be enrolled as soon as the exclusion has resolved.

1. Alanine aminotransferase (ALT) \>2.5 times the upper limit of normal.
2. Hemoglobin \<8.5 g/dl.
3. Moderate or severe pitting edema of the feet or legs (IRIS grade 3 or 4).
4. Carotid surgery or carotid stenting procedure scheduled (delay randomization until 2 weeks following procedure).
D: Inclusion Criteria:

* Men or women with: a) newly detected type 2 diabetes based on a fasting plasma glucose greater than or equal to 7.0 mmol/l (126 mg/dL) or a 2 hour plasma glucose (FPG) greater than or equal to 11.1 mmol/l (200 mg/dL) on an oral glucose tolerance test, or b) a history of type 2 diabetes
* Hemoglobin A1c (A1C) 6.5-9.5% inclusive (for assays with upper limit of normal of 6%) within one month of screening
* Age ≥ 50 years and evidence of vascular disease defined as ≥1of:

  * prior myocardial infarction
  * prior stroke
  * coronary, carotid or peripheral artery revascularization ≥ 4 years earlier
  * previous documented myocardial ischemia on either an exercise stress test or on any cardiac imaging, or previous unstable angina with ECG changes or cardiac enzyme elevation OR
* Age ≥ 55 years and evidence of subclinical vascular disease defined as ≥1 of:

  * microalbuminuria or proteinuria
  * history of treated or untreated hypertension with left ventricular hypertrophy by electrocardiogram (ECG) or echocardiogram

    * 50% stenosis on any imaging of coronary, carotid or lower extremity arteries
  * ankle/brachial index \<0.9 OR
* Age ≥ 60 years and at least 2 of the following cardiovascular disease risk factors:

  * current tobacco use
  * LDL-c ≥3.4 mmol/L (130 mg/dL) or on a lipid lowering medication
  * HDL-c \< 1.0 mmol/L (40 mg/dL) for men and \< 1.3 mmol/L (50 mg/dL) for women or triglycerides ≥ 2.3 mmol/L (200 mg/dL)
  * BP lowering medication use or untreated SBP ≥ 140 mmHg or DBP ≥ 95 mmHg
  * Waist to hip ratio \> 1.0 for men and \> 0.8 for women
* On no insulin and on less than or equal to 2 anti-diabetes drugs where at least one drug is at or below the half-maximal dose (as indicated in the MOP) with stable dosing for 10 weeks prior to screening

Exclusion Criteria:

* Type 1 diabetes
* Current need for insulin treatment
* Symptomatic hyperglycemia requiring immediate therapy in the judgment of the physician
* An acute cardiovascular event within 30 days prior to randomization
* Symptomatic heart failure (i.e. New York Heart Association class II or higher) or any episode of previous pulmonary edema or known ejection fraction \< 0.4 or current use of loop diuretics
* Any fracture within the past 1 year
* Currently planned coronary, carotid or peripheral artery revascularization or cardiac valve surgery
* Coronary, carotid or peripheral artery revascularization within the 4 years prior to screening in the absence of angina, MI, or stroke in the intervening period
* End stage renal disease requiring renal replacement therapy
* Receiving drug therapy to treat liver disease
* A diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or adequately treated cervical carcinoma in situ) in the past 3 years or current treatment for the active cancer (other than prophylactic)
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level \> 2.5 times the upper limit of normal
* A prior heart transplant or awaiting a heart transplant
* Previous or current hypercalcemia, hyperparathyroidism, osteomalacia or other contraindication for vitamin D therapy
* Regular use of or indication for greater than 400IU of vitamin D daily
* Clinically or medically unstable with expected survival \< 1 year
* Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant's data
* Any other factor likely to limit protocol compliance or reporting of adverse events
* Inability to discontinue a TZD (if taking one) in the judgement of the physician/investigator
* Contraindications to or history of hypersensitivity to the investigational products
* History of renal stones within the past 2 years
* Participation in another clinical trial of an investigational agent

Answer: B