Detection/Exclusion of cerebral ß-amyloid. To determine the sensitivity and specificity of the visual assessment of regional tracer uptake in the BAY 94-9172 PET images compared to histological verification of the presence or absence of cerebral ß-amyloid in the respective postmortem specimens as the standard of truth. MedDRA version: 19.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: Florbetaben (BAY 94-9172)
Product Code: ([F-18]AV1/ZK)
Pharmaceutical Form: Radiopharmaceutical precursor
INN or Proposed INN: Florbetaben (18 F)
Current Sponsor code: BAY 94-9172
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Sponsors
Bayer AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects with a low probability of cerebral ß-amyloid deposition, e.g. non-demented volunteers and subjects with a high probability of ß-amyloid deposition, e.g.patients diagnosed with AD or Dementia with Lewy Bodies (DLB), 10 cognitively normal and young healthy volunteers between 21 and 40 years of age. Each study participant has to meet the following criteria: - is at least 21 years of age - females, no child-bearing potential or negative urine pregnancy test on day of BAY 94-9172 injection - exhibits visual, auditory, and communicative capabilities adequate to provide informed consent or assent and comply with study procedures - is willing and able to lie down in MRI and PET scanners - is willing to donate their brain for postmortem examination in case of death (this consent can be obtained in the manner specific to the country/region involved and is not required of the 10 young healthy volunteer study participants) - the subject, or the subject and its legally acceptable representative (e.g., for probable AD and DLB patients), will be compliant and have a high probability of completing the study in the opinion of the investigator - has been fully informed about the study, including provisions of the Health Insurance Portability and Accountability Act (HIPAA), as applicable, and informed consent or assent has been signed and dated (with time) by the subject and/or the subject's legally acceptable representative (e.g., for probable AD and DLB patients) - the subject who has participated in a previous florbetaben study eg, study 311741, may be included in the present study. The MRI- and florbetaben PET scan do not need to be repeated if both scans were performed within twelve months prior to inclusion. Inclusion criteria for the additional 10 negative controls only - is = 21 to = 40 years of age - has no evidence of cognitive impairment as indicated by a clinical dementia rating (CDR, Hughes et al, 1982) score of 0 (zero) and a score of = 28 in the Mini-Mental Status Examination (MMSE, Folstein et al, 1975) - has no evidence of cognitive impairment as indicated by the CERAD neuropsychological test battery based on the results of each of the subtests (except MMSE which is covered by criterion 9 above) - has MRI brain scan that has been judged as "normal (age-appropriate)" including ARWMC scale (Wahlund et al, 2001) scores supporting the lack of cerebrovascular disease (e.g., a white matter lesion score of 0 or 1 or 2 and a basal ganglia score of 0 or 1) and a Scheltens scale (Scheltens et al, 1992) verifying the lack of cerebral atrophy (e.g., bilateral temporal lobe atrophy visual score of 0 or 1). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 174
Exclusion criteria
Exclusion criteria: Each subject who meets any of the following criteria must not participate in this study: - has severe cerebral macrovascular (i.e., multi-stroke) disease or brain tumor (metastasis/brain cancer) as verified by MRI - has any contraindication to magnetic resonance imaging (MRI) examination, e.g. metal implants or phobia as determined by the onsite radiologist performing the scan - is scheduled for surgery and/or another invasive procedure within the time period of up to 7 days following study drug administration - is allergic to the study drug or any of its constituents - has received any contrast material (X-ray, MRI) or radiopharmaceutical within 48 hours prior to or a therapeutic radiopharmaceutical (e.g. 131I) within 10 days prior to the administration of the study drug or for whom administration of such substances is planned within 7 days following study drug administration - has been previously enrolled in this study or participated in a clinical study involving an investigational pharmaceutical product within 30 days prior to treatment and/or was administered a radiopharmaceutical within 10 radioactive half-lives to study drug administration in this study* - has severe cardio-vascular instability requiring intensive care surveillance and/or therapeutic intervention (i.e., catecholamine infusion) *NOTE for subjects in Germany only: According to the German Radiation Protectin Law, subjects in Germany with a low probability of cerebral ß-amyloid deposition in the brain are not allowed to receive more than 10 mSv of radiation within a 10 year period and therefore will undergo the initial PET scan only; the yearly follow-up PET scans are prohibited.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the sensitivity and specificity of the visual assessment of regional tracer uptake in the BAY 94-9172 PET images compared to histological verification of the presence or absence of cerebral ß-amyloid in the respective postmortem specimens as the standard of truth.;Secondary Objective: To determine the sensitivity and specificity of the composite "whole brain" regional visual assessment collapsed from the regional PET visual assessment results in detecting/excluding cerebral ß-amyloid plaques based on the "whole brain" histopathological verification of the presence/absence of ß-amyloid deposition. To determine the sensitivity and specificity of the quantitative assessment of regional tracer uptake in BAY 94-9172 PET images compared to histological verification of the presence or absence of cerebral ß-amyloid in the respective postmortem specimens as the standard of truth. To determine the sensitivity and specificity of the visual assessment of BAY 94-9172 PET images on the subject level (according to the RCTU and BAPL rating scale) in detecting/excluding cerebral ß-amyloid compared to the onsite neuropathological diagnosis as the standard of reference. To evaluate the safety and tolerability of a single dose of BAY 94-9172 (ZK 6013443).;Primary end point(s): The co-primary efficacy variables of the study will be the sensitivity and specificity of the visual assessment of regional tracer uptake in the BAY 94-9172 PET images in correctly differentiating between brain regions with and without ß-amyloid deposition. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine the sensitivity and specificity of the composite “whole brain” (per subject) regional visual assessment collapsed from the regional PET visual assessment results in detecting/excluding cerebral ß-amyloid plaques based on the "whole brain" histopathological verification of the presence/absence of ß-amyloid deposition (collapsed from the results of the regional histological findings from the Pathology Consensus Panel). To determine the sensitivity and specificity of the quantitative assessment of regional tracer uptake in BAY 94-9172 PET images compared to histological verification of the presence or absence of cerebral ß-amyloid in the respective postmortem specimens as the standard of truth. To determine the sensitivity and specificity of the visual assessment of BAY 94-9172 PET images on the subject level (according to the RCTU and BAPL rating scale) in detecting/excluding cerebral ß-amyloid compared to the onsite neuropathological diagnosis as the standard of reference. To evaluate the safety and tolerability of a single dose of BAY 94-9172 (ZK 6013443). To perform an exploratory investigation of the association between the subject level visual assessment of BAY 94-9172 and FDG PET images for detecting the abnormalities in patients with AD compared to individuals with other types of dementia and/or without cognitive impairment. The on-site clinical diagnosis (if available) will serve as the reference standard. To investigate the association between the visual assessments of the regional tracer uptake apparent in BAY 94-9172 PET images and the regional glucose hypometabolism as seen in the FDG PET images in patients with AD compared to individuals with other types of dementia and/or without cognitive impairment. | — |
Countries
Australia, France, Germany, Japan, United States
Contacts
Public ContactBayer Clin. Trials Contact CTP Team
Bayer AG
Outcome results
None listed