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
Condition: Mild Cognitive Impairment Due to Alzheimer's Disease
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Intervention: Pioglitazone; Placebo
Intervention description: Pioglitazone tablets; Pioglitazone placebo-matching tablets
Intervention MeSH terms: Pioglitazone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study is to evaluate the effect of pioglitazone at 24 months compared
      with placebo on cognitive decline in high-risk participants who have completed the
      AD-4833/TOMM40_301 study [NCT01931566] with an adjudicated diagnosis of mild cognitive
      impairment (MCI) due to Alzheimer's Disease (AD).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Completed the pivotal AD-4833/TOMM40_301 study with an adjudicated diagnosis of mild
             cognitive impairment (MCI) due to Alzheimer's Disease (AD) without ongoing serious
             adverse events (SAEs) from AD-4833/TOMM40_301.

          2. Is male or female and is at least 65 years of age at the time of the Baseline Visit.

          3. In the opinion of the investigator, is capable of understanding and complying with the
             protocol requirements.

          4. The participant or, when applicable, the participant's legally acceptable
             representative signs and dates a written, informed consent form and any required
             privacy authorization prior to the initiation of any study procedures.

          5. Must be living independently or in nonmedical residential care.

          6. Has a project partner able to separately consent on his/her own behalf and take part
             in the study (with the intent to do so as long as the participant is enrolled),
             providing information on the cognitive, functional, and behavioral status of the
             participant and assisting with observation of adverse events (AEs) and monitoring of
             study medication, if needed. Project partners participating in the pivotal
             AD-4833/TOMM40_301 study are encouraged to participate in this extension study in this
             capacity.

        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.

         11. Has any cancer that has been in remission for less than 2 years from the extension
             study Baseline Visit. Participants with basal cell or stage I squamous cell carcinoma
             of the skin will be eligible. Participants with current diagnosis of bladder cancer
             are not eligible irrespective of the remission status.

         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.