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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01931566




Registration number
NCT01931566
Ethics application status
Date submitted
26/08/2013
Date registered
29/08/2013

Titles & IDs
Public title
Biomarker Qualification for Risk of Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease (AD) and Safety and Efficacy Evaluation of Pioglitazone in Delaying Its Onset
Scientific title
A Double Blind, Randomized, Placebo Controlled, Parallel Group Study to Simultaneously Qualify a Biomarker Algorithm for Prognosis of Risk of Developing Mild Cognitive Impairment Due to Alzheimer's Disease (MCI Due to AD) and to Test the Safety and Efficacy of Pioglitazone (AD-4833 SR 0.8 mg QD) to Delay the Onset of MCI Due to AD in Cognitively Normal Subjects
Secondary ID [1] 0 0
2012-003111-58
Secondary ID [2] 0 0
AD-4833/TOMM40_301
Universal Trial Number (UTN)
Trial acronym
TOMMORROW
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Cognitive Impairment Due to Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pioglitazone
Treatment: Drugs - Pioglitazone placebo

Placebo comparator: Low Risk Placebo - Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to low risk group for developing MCI-AD for up to 5 years.

Placebo comparator: High Risk Placebo - Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.

Experimental: High Risk Pioglitazone - Pioglitazone 0.8 mg, sustained release (SR) tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.


Treatment: Drugs: Pioglitazone
Pioglitazone SR tablets

Treatment: Drugs: Pioglitazone placebo
Pioglitazone placebo-matching tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Diagnosis of Mild Cognitive Impairment Due to Alzheimer's Disease (MCI-AD) for Placebo-treated, High-risk, Non-Hispanic/Latino Caucasian Participants Versus Placebo-treated, Low-risk, Non-Hispanic/Latino Caucasian Participants
Timepoint [1] 0 0
Baseline to the end of study (approximately up to 5 years)
Primary outcome [2] 0 0
Time to Diagnosis of MCI Due to AD for Pioglitazone-treated, High-risk, Non-Hispanic/Latino Caucasian Participants Versus Placebo-treated, High-risk, Non-Hispanic/Latino, Caucasian Participants
Timepoint [2] 0 0
Baseline to the end of study (approximately up to 5 years)
Secondary outcome [1] 0 0
Change From Baseline for Cognitive Decline on Composite Score on the Cognitive Test Battery for Pioglitazone-treated Participants Versus Placebo-treated Participants in the High-risk Stratum
Timepoint [1] 0 0
Baseline and Month 48
Secondary outcome [2] 0 0
Change From Baseline in Instrumental Activities of Daily Living (Alzheimer's Disease Cooperative Study Activities of Daily Living - Prevention Instrument [ADCS ADL-PI]) Between Pioglitazone-treated and Placebo-treated Groups of the High-risk Stratum
Timepoint [2] 0 0
Baseline and Month 48

Eligibility
Key inclusion criteria
1. In the opinion of the investigator, participant is capable of understanding and complying with protocol requirements.
2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Is able to physically perform the cognitive tests in the opinion of the investigator and is fluent in the language that tests will be administered.
4. Is cognitively normal at baseline, scoring as indicated for the following tests:

* Clinical Dementia Rating (CDR)=0.
* At least one memory test above -1.5 standard deviation (SD) of the demographically corrected normative mean.
5. Must score =25 on the Mini-Mental State Examination (MMSE) at the screening visit after the education and age adjustment.
6. Is male or postmenopausal female between the ages of 65 and 83 years, inclusive, at time of the Screening visit.
7. Has the ability and intention to participate in regular study visits, in the opinion of the Investigator.
8. Has a project partner who can separately complete an Acknowledgement Form on his/her own behalf and take part in the study (with the intent to do so as long as the participant is enrolled) to provide information on the cognitive, functional, and behavioral status of the participant and to assist with monitoring of study medication, if needed.
Minimum age
65 Years
Maximum age
83 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Has a current diagnosis or history of any type of cognitive impairment or dementia or has a current diagnosis or history of neurological/psychiatric disorder or any other diagnosis that significantly affects cognitive performance (eg, mental retardation, organic mental disorder).
2. Has a current diagnosis of significant psychiatric illness, per Diagnostic & Statistical Manual of Mental Disorders, 4th Edition - Text Revision (DSM-IV-TR) (or DSM-V when published) (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) >8.0% at the time of baseline or requires treatment with insulin, triple oral antidiabetic therapy or a peroxisome proliferator-activated receptor-gamma (PPAR-?) agonist. The participant should be on a stable antidiabetic regimen for at least 3 months prior to enrollment.
4. Has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or cardiovascular, pulmonary, gastrointestinal (including s/p gastric bypass), endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. History of HIV infection is considered exclusionary for this study.
5. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse/dependence within 2 years prior to the Screening Visit.
6. Is an immediate family member, testing center employee, or is in a dependent relationship with a testing center employee who is involved in conduct of this study (eg, spouse, parent, child, and sibling) or may consent under duress.
7. Has a history of hypersensitivity or allergies to pioglitazone or related compounds.
8. Is required to take excluded medications as specified in the Excluded Medications Section.
9. Had any of the following values at the Baseline Visit (Visit 2):

1. A serum total bilirubin value >1.5× upper limit of normal (ULN).
2. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2xULN.
3. Unexplained microscopic/macroscopic hematuria on one repeat examinations within 2 weeks of the initial assessment.
10. Is positive for either Hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) antibodies at the Baseline Visit (Visit 2).
11. Has a condition 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.
12. Has received any investigational compound within 30 days prior to screening or 5 half-lives prior to Screening or is currently participating in another study which entails the administration of an investigational or marketed drug, supplement or intervention including, but not limited to diet, exercise, lifestyle or invasive procedure.
13. Has a history of any cancer that has been in remission for less than 2 years from the Screening Visit. Participants with basal cell or stage I squamous cell carcinoma of the skin will be eligible. Participants with history of bladder cancer are not eligible irrespective of the remission status.
14. Has a history or current diagnosis of macular edema or macular degeneration.
15. If female, has a history of postmenopausal fractures with no or minimal trauma (eg, wrist, hip, lumbar or thoracic vertebral fracture).
16. Has a history or current diagnosis of congestive heart failure (CHF), New York Heart Association Class III-IV.
17. Has been exposed to the cognitive tests performed in this study within 6 months prior to the Screening Visit, with the exception of the MMSE.
18. Participant's Translocase of the Outer Mitochondrial Membrane 40 homolog (TOMM40) rs10524523 or apolipoprotein E (APOE) genotypes or APOE phenotype are known by the participant or the study staff participating in this study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/09/2018
Sample size
Target
Accrual to date
Final
3494
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
- North Ryde
Recruitment hospital [2] 0 0
- Southport
Recruitment hospital [3] 0 0
- West Heidelberg
Recruitment hospital [4] 0 0
- Nedlands
Recruitment postcode(s) [1] 0 0
- North Ryde
Recruitment postcode(s) [2] 0 0
- Southport
Recruitment postcode(s) [3] 0 0
- West Heidelberg
Recruitment postcode(s) [4] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Nevada
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Wisconsin
Country [20] 0 0
Germany
State/province [20] 0 0
Baden Wuerttemberg
Country [21] 0 0
Germany
State/province [21] 0 0
Nordrhein Westfalen
Country [22] 0 0
Germany
State/province [22] 0 0
Sachsen Anhalt
Country [23] 0 0
Germany
State/province [23] 0 0
Berlin
Country [24] 0 0
Switzerland
State/province [24] 0 0
Basel
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Devon
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Greater London
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Greater Manchester
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Lancashire
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Middlesex
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Strathclyde
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Tayside Region
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Bristol

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Zinfandel Pharmaceuticals Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com 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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01931566