Mild cognitive impairment due to Alzheimer’s disease MedDRA version: 18.1 Level: LLT Classification code 10009846 Term: Cognitive impairment System Organ Class: 100000004852
Conditions
Interventions
Product Name: pioglitazone sustained-release
Product Code: AD-4833 SR
Pharmaceutical Form: Tablet
INN or Proposed INN: pioglitazone
CAS
Sponsors
Takeda Development Centre Europe Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or postmenopausal female subject between 65 and 83 years of age, inclusive at the time of the screening visit. 2. The subject must be cognitively normal at baseline, scoring as indicated for the following tests: - Clinical Dementia Rating (CDR)=0. - At least one memory test above -1.5 SD of the demographically corrected normative mean. 3. The subject must score =25 on the Mini Mental Status Examination (MMSE) at the screening visit after the education and age adjustment referenced in Appendix G of the protocol. 4. All subjects require a project partner who can separately complete an Acknowledgment Form on his/her own behalf and take part in the study to provide information on the cognitive, functional, and behavioral status of the subject and to assist with monitoring of study medication, if needed. 5. The subject has the ability and intention to participate in regular study visits, in the opinion of the Investigator. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3500
Exclusion criteria
Exclusion criteria: 1. The subject 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. The subject has a current diagnosis of significant psychiatric illness, per the Diagnostic & Statistical Manual of Mental Disorders, 4th Edition - Text Revision (DSM-IV-TR) (including but not limited to major depressive disorder, anxiety disorders) and is in an acute phase/episode, or the subject has a current diagnosis or history of schizophrenia or bipolar disorder. 3. The subject has 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 agonist. The subject should be on a stable antidiabetic regimen for at least 3 months prior to enrollment. 4. The subject has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. History of HIV infection is considered exclusionary for this study. 5.The subject 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.The subject has a history or current diagnosis of macular edema or macular degeneration. 7. If female, the subject has a history of postmenopausal fractures with no or minimal trauma (eg, wrist, hip, lumbar or thoracic vertebral fracture). 8. The subject has a history or current diagnosis of congestive heart failure (CHF), New York Heart Association Class III-IV. 9. The subject has been exposed to cognitive tests performed in this study within 6 months prior to the Screening Visit with the exception of the MMSE. 10. The subject’s TOMM40 rs10524523 or APOE genotypes or APOE phenotype are known by the subject or the study staff participating in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: MCI event could occur at any time during the study, so there is no fixed timepoint for evaluation of an individual event. ; Main Objective: For biomarker risk algorithm qualification: -To qualify the biomarker risk algorithm composed of TOMM40 rs10524523 genotype, APOE genotype, and age for prognosis of the risk of developing MCI due to AD within 5 years. For efficacy evaluation of pioglitazone: - To evaluate the efficacy of pioglitazone compared with placebo to delay the onset of MCI due to AD in cognitively-normal subjects who are at high-risk, as identified by the biomarker risk algorithm at enrollment, for developing MCI due to AD within 5 years. ; Secondary Objective: -To evaluate the effect of pioglitazone compared with placebo on the progression of cognitive decline. -To evaluate the effect of pioglitazone compared with placebo on functional decline and instrumental activities of daily living. ; Primary end point(s): For biomarker risk algorithm qualification: -Time to diagnosis of MCI due to AD for placebo-treated, high-risk, non-Hispanic/Latino Caucasian subjects versus placebo-treated, low-risk, non-Hispanic/Latino Caucasian subjects. For efficacy evaluation of pioglitazone: Time to diagnosis of MCI due to AD for pioglitazone-treated, non-Hispanic/Latino Caucasian subjects versus placebo-treated non-Hispanic/Latino, Caucasian subjects in the high-risk stratum. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Change from baseline for cognitive decline on composite score on the cognitive battery for pioglitazone-treated subjects versus placebo-treated subjects in the high-risk stratum. - Changes 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(s) of evaluation of this end point: Change from baseline to event which could occur at any time during the study. | — |
Countries
Australia, Germany, Italy, Switzerland, United Kingdom, United States
Contacts
Public ContactStudy Manager
Takeda Development Centre Europe Ltd
Outcome results
None listed