Mild Cognitive Impairment Due to Alzheimer's DiseasePhase 3NCT02284906
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 Phase 3 study testing Pioglitazone in people with Mild Cognitive Impairment Due to Alzheimer's Disease, run by Takeda at 43 sites in 4 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Mild Cognitive Impairment Due to Alzheimer's Disease
- What is being tested?
- Pioglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 43 sitesin 4 countries
- Study dates
- 12 Feb 2015to 8 May 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
- Has a history or current diagnosis of congestive heart failure (CHF), New York Heart Association class III-IV.
Trial locations and contacts
43 sites in 4 countries.
43 sites in 4 countries
United States28 sites
Study site
Akron, Ohio, 44320
Study site
Atlanta, Georgia, 30329
Study site
Charleston, South Carolina, 29401
Study site
Chicago, Illinois, 60640
Study site
Concord, North Carolina, 28025
Study site
Decatur, Georgia, 30033
Study site
Delray Beach, Florida, 33445
Study site
Durham, North Carolina, 27705
Study site
Elk Grove, Illinois, 60007
Study site
Elk Grove Village, Illinois, 60007
Study site
Fort Myers, Florida, 33912
Study site
Houston, Texas, 77030
Study site
Iowa City, Iowa, 52242
Study site
Lake Worth, Florida, 33449
Study site
Las Vegas, Nevada, 89106
Study site
Marlton, New Jersey, 08053
Study site
Melbourne, Florida, 32940
Study site
Merritt Island, Florida, 32952
Study site
Middleton, Wisconsin, 53562
Study site
New York, New York, 10019
Study site
Phoenix, Arizona, 85006
Study site
Port Orange, Florida, 32127
Study site
Salt Lake City, Utah, 84107
Study site
San Diego, California, 92103
Study site
St Louis, Missouri, 63141
Study site
St. Petersburg, Florida, 33709
Study site
Sun City, Arizona, 85351
Study site
Weston, Florida, 33331
United Kingdom10 sites
Study site
Blackpool, Lancashire, FY2 0JH
Study site
Bristol, Avon, BS16 1LE
Study site
Exeter, Devon, EX2 5DW
Study site
Glasgow, Strathclyde, G20 0XA
Study site
Hammersmith, Greater London, W6 8RF
Study site
Isleworth, Middlesex, TW7 6FY
Study site
London, Greater London, EC1M 6BQ
Study site
Manchester, Greater Manchester, M13 9NQ
Study site
Perth, Tayside Region, PH2 7BH
Study site
Plymouth, Devon, PL6 8DH
Australia4 sites
Study site
Heidelberg West, Victoria, 3081
Study site
Nedlands, Western Australia, 6009
Study site
North Ryde, New South Wales, 2113
Study site
Southport, Queensland, 4215
About this study
Official title: 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
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).
Read the 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.
- Being tested
- Pioglitazone, Placebo
- Keywords
- Drug therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called AD-4833
Pioglitazone tablets
PlaceboDrug
Pioglitazone placebo-matching tablets
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone 0.8 mg | Experimental | Pioglitazone 0.8 mg, tablets, orally, once, daily, for minimum of 2 years. Receives: Drug: Pioglitazone |
| Placebo | Placebo comparator | Pioglitazone placebo-matching tablets, orally, once, daily, for minimum of 2 years. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Month 24
Secondary outcomes (1)
Time to Diagnosis of Alzheimer's Disease (AD) Dementia
Measured: Day 1 and every 6 months (up to maximum of 36 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2014 (estimated)
- Study start12 Feb 2015
- Primary completion31 Jan 2018
- Study completion8 May 2018
Why it stopped: Lack of efficacy of the drug; no safety concern
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mild Cognitive Impairment Due to Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02284906
- Sponsor's protocol ID
- AD-4833/TOMM40_303
- Other IDs
- U1111-1154-9637, 2013-004984-30
- Status last verified
- Jun 2019
- First submitted
- 4 Nov 2014
- Last updated
- 2 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02284906
- Acronym / sponsor ID
- AD-4833/TOMM40_303
- Keywords
- Drug therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy of the drug; no safety concern
- Enrolment
- 40 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 12 Feb 2015 (actual)
- Primary completion
- 31 Jan 2018 (actual)
- Study completion
- 8 May 2018 (actual)
- First posted
- 6 Nov 2014 (estimated)
- Results
- Posted 2 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone 0.8 mg | Experimental | Drug: PioglitazonePioglitazone 0.8 mg, tablets, orally, once, daily, for minimum of 2 years. |
| Placebo | Placebo comparator | Drug: PlaceboPioglitazone placebo-matching tablets, orally, once, daily, for minimum of 2 years. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneAlso: AD-4833Pioglitazone tablets | Drug | Pioglitazone 0.8 mg |
| PlaceboPioglitazone placebo-matching tablets | Drug | Placebo |
Primary outcome
Change From Extension Study Baseline in Composite Score of a Broad Cognitive Test Battery at Month 24
Time frame: Baseline and 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.
1 secondary outcome
Time to Diagnosis of Alzheimer's Disease (AD) Dementia
Time frame: Day 1 and every 6 months (up to maximum of 36 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director Clinical Science study director
Takeda
43 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pioglitazone in people with Mild Cognitive Impairment Due to Alzheimer's Disease, run by Takeda at 43 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States, United Kingdom, Australia, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Extension Study Baseline in Composite Score of a Broad Cognitive Test Battery at Month 24 (time frame: Baseline and Month 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2019.