Study Stopped
Lack of efficacy of the drug; no safety concern
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
A Blinded Long-term Extension Study to Evaluate the Safety and Efficacy of Pioglitazone (AD-4833 Sustained Release 0.8 mg Daily) to Slow the Progression of Cognitive Decline in Subjects Who Have Completed the AD-4833/TOMM40_301 Study With Diagnosis of Mild Cognitive Impairment Due to Alzheimer Disease
3 other identifiers
interventional
40
4 countries
43
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Feb 2015
Typical duration for phase_3
43 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 4, 2014
CompletedFirst Posted
Study publicly available on registry
November 6, 2014
CompletedStudy Start
First participant enrolled
February 12, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
May 8, 2018
CompletedResults Posted
Study results publicly available
July 2, 2019
CompletedJuly 2, 2019
June 1, 2019
3 years
November 4, 2014
May 7, 2019
June 11, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Extension Study Baseline in Composite Score of a Broad Cognitive Test Battery at Month 24
Composite scores were derived from the test battery. Each test in the battery falls into 1 of the following cognitive domains: Episodic Memory (California Verbal Learning Test - 2nd Edition \[CVLT-II\], Brief Visuospatial Memory Test - Revised \[BVMT-R\]), Executive Function (Trail Making Part B, Digit Span Backwards), Language (Animals, Lexical/Phonemic Fluency), Attention (Digit Span Forward, Trail Making Part A), and Visuospatial (Clock Drawing, BVMT-Copy). Only the domains of episodic memory, executive function, language, and attention were used for the calculation of composite score (i.e., Clock Drawing, BVMT-Copy, and the Multilingual Naming Test (MINT), which do not allow generation of standard z scores, were only used for diagnostic purposes and were excluded from the calculation of the composite score). To form the composite, z-scores were calculated for each test, each z-score for the domain were averaged, and then all relevant domains were averaged to form the composite.
Baseline and Month 24
Secondary Outcomes (1)
Time to Diagnosis of Alzheimer's Disease (AD) Dementia
Day 1 and every 6 months (up to maximum of 36 months)
Study Arms (2)
Pioglitazone 0.8 mg
EXPERIMENTALPioglitazone 0.8 mg, tablets, orally, once, daily, for minimum of 2 years.
Placebo
PLACEBO COMPARATORPioglitazone placebo-matching tablets, orally, once, daily, for minimum of 2 years.
Interventions
Eligibility Criteria
You may qualify if:
- 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.
- Is male or female and is at least 65 years of age at the time of the Baseline Visit.
- In the opinion of the investigator, is capable of understanding and complying with the protocol requirements.
- 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.
- Must be living independently or in nonmedical residential care.
- 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.
You may not qualify if:
- Completed the pivotal AD-4833/TOMM40\_301 study with an adjudicated diagnosis of AD dementia.
- 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.
- 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.
- 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.
- 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.
- Is required to take excluded medications.
- Has a history of hypersensitivity or allergies to pioglitazone or related compounds.
- Had any of the following values at the extension study Baseline Visit:
- A serum total bilirubin value \>15 x upper limit of normal (ULN).
- A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \>2 x ULN.
- Unexplained microscopic/macroscopic hematuria on 2 repeat examinations within 2 weeks.
- 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.
- 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.
- 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.
- Has a current diagnosis of macular edema, degeneration or any maculopathy.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (43)
Unknown Facility
Phoenix, Arizona, 85006, United States
Unknown Facility
Sun City, Arizona, 85351, United States
Unknown Facility
San Diego, California, 92103, United States
Unknown Facility
Delray Beach, Florida, 33445, United States
Unknown Facility
Fort Myers, Florida, 33912, United States
Unknown Facility
Lake Worth, Florida, 33449, United States
Unknown Facility
Melbourne, Florida, 32940, United States
Unknown Facility
Merritt Island, Florida, 32952, United States
Unknown Facility
Port Orange, Florida, 32127, United States
Unknown Facility
St. Petersburg, Florida, 33709, United States
Unknown Facility
Weston, Florida, 33331, United States
Unknown Facility
Atlanta, Georgia, 30329, United States
Unknown Facility
Decatur, Georgia, 30033, United States
Unknown Facility
Chicago, Illinois, 60640, United States
Unknown Facility
Elk Grove, Illinois, 60007, United States
Unknown Facility
Elk Grove Village, Illinois, 60007, United States
Unknown Facility
Iowa City, Iowa, 52242, United States
Unknown Facility
St Louis, Missouri, 63141, United States
Unknown Facility
Las Vegas, Nevada, 89106, United States
Unknown Facility
Marlton, New Jersey, 08053, United States
Unknown Facility
New York, New York, 10019, United States
Unknown Facility
Concord, North Carolina, 28025, United States
Unknown Facility
Durham, North Carolina, 27705, United States
Unknown Facility
Akron, Ohio, 44320, United States
Unknown Facility
Charleston, South Carolina, 29401, United States
Unknown Facility
Houston, Texas, 77030, United States
Unknown Facility
Salt Lake City, Utah, 84107, United States
Unknown Facility
Middleton, Wisconsin, 53562, United States
Unknown Facility
North Ryde, New South Wales, 2113, Australia
Unknown Facility
Southport, Queensland, 4215, Australia
Unknown Facility
Heidelberg West, Victoria, 3081, Australia
Unknown Facility
Nedlands, Western Australia, 6009, Australia
Unknown Facility
Basel, CH-4012, Switzerland
Unknown Facility
Bristol, Avon, BS16 1LE, United Kingdom
Unknown Facility
Exeter, Devon, EX2 5DW, United Kingdom
Unknown Facility
Plymouth, Devon, PL6 8DH, United Kingdom
Unknown Facility
Hammersmith, Greater London, W6 8RF, United Kingdom
Unknown Facility
London, Greater London, EC1M 6BQ, United Kingdom
Unknown Facility
Manchester, Greater Manchester, M13 9NQ, United Kingdom
Unknown Facility
Blackpool, Lancashire, FY2 0JH, United Kingdom
Unknown Facility
Isleworth, Middlesex, TW7 6FY, United Kingdom
Unknown Facility
Glasgow, Strathclyde, G20 0XA, United Kingdom
Unknown Facility
Perth, Tayside Region, PH2 7BH, United Kingdom
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director Clinical Science
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NON RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 4, 2014
First Posted
November 6, 2014
Study Start
February 12, 2015
Primary Completion
January 31, 2018
Study Completion
May 8, 2018
Last Updated
July 2, 2019
Results First Posted
July 2, 2019
Record last verified: 2019-06
Data Sharing
- IPD Sharing
- Will share
Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.