AD-4833/TOMM40_303 Extension Study of the Safety and Efficacy of Pioglitazone to Slow Cognitive Decline in Participants With Mild Cognitive Impairment Due to Alzheimer Disease

Exclusion Criteria

• •1. Completed the pivotal AD-4833/TOMM40\_301 study with an adjudicated diagnosis of AD dementia.
• •2. Has a current diagnosis of significant psychiatric illness, per Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (including but not limited to major depressive disorder, anxiety disorders) and is in an acute phase/episode, or the participant has a current diagnosis or history of schizophrenia or bipolar disorder.
• •3. Has a glycosylated hemoglobin (HbA1c) \>8% at the extension study Baseline Visit or requires treatment with insulin, triple oral antidiabetic therapy or a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist.
• •4. Has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or cardiovascular, pulmonary, gastrointestinal (including s/p gastric bypass surgery), endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance.
• •5. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, pivotal, child, sibling) or may consent under duress.
• •6. Is required to take excluded medications.
• •7. Has a history of hypersensitivity or allergies to pioglitazone or related compounds.
• •8. Had any of the following values at the extension study Baseline Visit:
• •1. A serum total bilirubin value \>15 x upper limit of normal (ULN).
• •2. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \>2 x ULN.
• •3. Unexplained microscopic/macroscopic hematuria on 2 repeat examinations within 2 weeks.
• •9. Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy, or prevent the participant from adequately participating in the study or continue for the anticipated duration of the study.
• •10. Has received any investigational compound, with the exception of treatment during the AD-4833/TOMM40\_301 study, within 30 days prior to Baseline or 5 half-lives prior to Baseline or is currently participating in another study that entails the administration of an investigational or marketed drug, supplement, or intervention including, but not limited to diet, exercise, lifestyle, or invasive procedure.
• •12. Has a current diagnosis of macular edema, degeneration or any maculopathy.
• •13. Has a history or current diagnosis of congestive heart failure (CHF), New York Heart Association class III-IV.