A Phase IIa Multi-Center Study of 18F-FDG PET, Safety, and Tolerability of AZD0530 in Mild Alzheimer's Disease
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|ClinicalTrials.gov Identifier: NCT02167256|
Recruitment Status : Completed
First Posted : June 19, 2014
Results First Posted : August 14, 2019
Last Update Posted : August 14, 2019
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|Condition or disease||Intervention/treatment||Phase|
|Alzheimer's Disease||Drug: AZD0530 100mg daily Drug: AZD0530 125mg daily Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||159 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase IIa Multi-Center Study of 18F-FDG PET, Safety, and Tolerability of AZD0530 in Mild Alzheimer's Disease|
|Actual Study Start Date :||December 2014|
|Actual Primary Completion Date :||February 27, 2018|
|Actual Study Completion Date :||February 27, 2018|
Experimental: AZD0530 100mg daily
Patients in the experimental group (50%) will be started on this dose. After 2 weeks, patients with a plasma drug level of <100ng/ml will receive 125mg AZD0530 daily and remain in the same experimental group as patient receiving 100mg daily.
Drug: AZD0530 100mg daily
All patients in experimental group (50%) will be started on 100mg AZD0530 daily
Other Name: saracatinib
Drug: AZD0530 125mg daily
Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily will receive 125mg daily of AZD0530.
Other Name: saracatinib
Placebo Comparator: AZD0530 Placebo
50% of patients will receive placebo treatment for the duration of the study,
50% of patients will receive placebo treatment for the duration of the study.
Other Name: saracatinib
- Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging [ Time Frame: 12 months ]Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.
- Number of Participants With One or More Serious/Other Adverse Events Subjects With Mild AD as Assessed by Analysis of Adverse Events, Including Symptoms, and Abnormal Findings on Physical and Neurological Examinations, and Standard Labs. [ Time Frame: 12 months ]Assessment of any adverse effects between drug and placebo-treated subjects
- The Effect of Treatment With AZD0530 on Cognitive and Behavioral Function [ Time Frame: 12 months ]
The change in cognitive function between baseline and 12 months will be measured by the following tests:
- Alzheimer Disease Assessment Scale - Cognitive 11 (ADAS-cog11). Measures: Cognitive function Maximum score: 70; Minimum score: 0. Higher score equals worse cognitive function
- Mini-Mental State Examination (MMSE) Measures: Cognitive Function Maximum score: 30; Minimum score: 0. Higher score equal better cognitive function
- Alzheimer Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) Measures: Ability to perform routine daily activities Maximum score: 78; Minimum score: 0. Higher score equals better ability to perform activities of daily living
- Clinical Dementia Rating Sum of Boxes (CDR-SO) Measures: Dementia severity Maximum score: 18; Minimum score: 0. Higher score equals more severe dementia.
- Percent Change in Brain Volume Before and After Treatment [ Time Frame: 12 months ]Change in volume of pre-defined brain regions between baseline and 12 months of treatment.
- Cerebrospinal Fluid Levels of Total Tau, Phospho-tau (p-Tau), and Amyloid-beta 1-42 (Abeta 1-42) [ Time Frame: 12 months ]Measure concentration of Tau and Amyloid-beta 1-42 biomarkers in the cerebrospinal fluid between baseline and 12 months of treatment
- Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging [ Time Frame: 12 months ]The results from the primary outcome with brain FDG-PET imaging was analyzed by ApoE genotype. Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.
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|Ages Eligible for Study:||55 Years to 85 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- NIA-Alzheimer's Association core clinical criteria for probable AD
- 18F-Florbetapir scan with evidence of elevated Aβ (based on central review)
- Age between 55-85 (inclusive)
- MMSE score between 18 and 26 (inclusive)
Stability of permitted medications for 4 weeks. In particular:
- Stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
- Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
- Geriatric Depression Scale less than 6 [Note: a score ≥6 on this screening scale may be permissible, if the subject is examined by a site clinician and judged not to be depressed.]
- Study partner is available who has frequent contact with the subject (e.g., average of 10 hours per week or more), and can accompany the subject to most visits to answer questions about the subject
- Visual and auditory acuity adequate for neuropsychological testing
- Good general health with no disease expected to interfere with the study
- Subject is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile)
- Modified Hachinski less than or equal to 4
- Completed six grades of education or has a good work history
- Must speak English or Spanish fluently
- Any significant neurologic disease other than AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
- Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions or multiple lacunes or lacunes in a critical memory structure
- Subjects that have any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker
- Major depression, bipolar disorder as described in DSM-IV within the past 1 year or psychotic features, agitation or behavioral problems within 3 months, which could lead to difficulty complying with the protocol
- History of schizophrenia (DSM V criteria)
- History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria)
- Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results, or the subject's ability to participate in the study.
- Has had a history within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment
- Clinically significant abnormalities in B12 or TFTs that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
- Residence in skilled nursing facility.
- Use of any excluded medication as described in study protocol
- Current or recent participation in any procedures involving radioactive agents, including current, past, or anticipated exposure to radiation in the workplace, such that the total radiation dose exposure to the subject in a given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1. This guideline is an effective dose of 5 rem received per year.
- Neutropenia defined as absolute neutrophils count of <1,800/microliter
- Thrombocytopenia defined as platelet count <120x103/microliter
- For CSF sub-study participants, a current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening
Clinically significant abnormalities in screening laboratories, including:
- Aspartate aminotransferase (AST) >1.5 times ULN
- Alanine aminotransferase (ALT) > 1.5 times ULN
- Total bilirubin >1.5 times ULN
- Serum creatinine >2.0 times ULN
- History of interstitial lung disease
- Patients whom the PI deems to be otherwise ineligible
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02167256
|Study Director:||Christopher H van Dyck, MD||Yale University|
|Study Director:||Paul Aisen, MD, PhD||USC Alzheimer's Therapeutic Research Institute (ATRI)|
Documents provided by Stephen M. Strittmatter, Yale University:
|Responsible Party:||Stephen M. Strittmatter, Professor of Neurology and Neurobiology, Yale University|
|Other Study ID Numbers:||
4UH3TR000967-02 ( U.S. NIH Grant/Contract )
|First Posted:||June 19, 2014 Key Record Dates|
|Results First Posted:||August 14, 2019|
|Last Update Posted:||August 14, 2019|
|Last Verified:||July 2019|
Central Nervous System Diseases
Nervous System Diseases
Molecular Mechanisms of Pharmacological Action