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

NCT ID: NCT02284906

Last Updated: 2019-07-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-12
• Study Completion Date: 2018-05-08

Brief 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).

Detailed Description

The drug being tested in this study is called pioglitazone. This study is designed to further evaluate the safety and effectiveness of pioglitazone on cognitive function in participants who have completed the AD-4833/TOMM40_301. This study will look at the effectiveness of pioglitazone on cognitive decline in high-risk participants who have completed the AD-4833/TOMM40_301 study with a diagnosis of mild cognitive impairment (MCI) due to Alzheimer's Disease (AD).

The study enrolled 40 participants, but is dependent on how many decide to continue treatment in an extension phase after completing the main (301) study. Participants will continue to receive the same study medication they received during the pivotal AD-4833/TOMM40_301 study, either:

• Pioglitazone 0.8 mg tablets or
• Placebo (this is a tablet that looks like the study drug but has no active ingredient).

All participants will be asked to take one tablet at the same time each day throughout the study.

This multi-centre trial, like its precedent pivotal trial, will be conducted worldwide. The overall time to participate in this study is minimum 2 years and a maximum of 7 years depending on when participants roll over from the 301 study. Participants will make approximately 2 visits per year to the clinic, and will be contacted by telephone 3 months after each treatment visit for a follow-up assessment, and 2 weeks after the final visit.

Conditions

Mild Cognitive Impairment Due to Alzheimer's Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pioglitazone 0.8 mg

Pioglitazone 0.8 mg, tablets, orally, once, daily, for minimum of 2 years.

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

Pioglitazone tablets

Placebo

Pioglitazone placebo-matching tablets, orally, once, daily, for minimum of 2 years.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pioglitazone placebo-matching tablets

Interventions

Pioglitazone

Pioglitazone tablets

Intervention Type: DRUG

Placebo

Pioglitazone placebo-matching tablets

Intervention Type: DRUG

Other Intervention Names

AD-4833

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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Phoenix, Arizona, United States

Sun City, Arizona, United States

San Diego, California, United States

Delray Beach, Florida, United States

Fort Myers, Florida, United States

Lake Worth, Florida, United States

Melbourne, Florida, United States

Merritt Island, Florida, United States

Port Orange, Florida, United States

St. Petersburg, Florida, United States

Weston, Florida, United States

Atlanta, Georgia, United States

Decatur, Georgia, United States

Chicago, Illinois, United States

Elk Grove, Illinois, United States

Elk Grove Village, Illinois, United States

Iowa City, Iowa, United States

St Louis, Missouri, United States

Las Vegas, Nevada, United States

Marlton, New Jersey, United States

New York, New York, United States

Concord, North Carolina, United States

Durham, North Carolina, United States

Akron, Ohio, United States

Charleston, South Carolina, United States

Houston, Texas, United States

Salt Lake City, Utah, United States

Middleton, Wisconsin, United States

North Ryde, New South Wales, Australia

Southport, Queensland, Australia

Heidelberg West, Victoria, Australia

Nedlands, Western Australia, Australia

Basel, , Switzerland

Bristol, Avon, United Kingdom

Exeter, Devon, United Kingdom

Plymouth, Devon, United Kingdom

Hammersmith, Greater London, United Kingdom

London, Greater London, United Kingdom

Manchester, Greater Manchester, United Kingdom

Blackpool, Lancashire, United Kingdom

Isleworth, Middlesex, United Kingdom

Glasgow, Strathclyde, United Kingdom

Perth, Tayside Region, United Kingdom

Countries

United States; Australia; Switzerland; United Kingdom

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

U1111-1154-9637

Identifier Type: REGISTRY

Identifier Source: secondary_id

2013-004984-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AD-4833/TOMM40_303

Identifier Type: -

Identifier Source: org_study_id