Phase II Study of Florbetaben (BAY 94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid in Patients With Probable Alzheimer's Disease Compared to Healthy Volunteers
The aim of this study is to evaluate the efficacy, safety of a single dose of BAY 94-9172 (ZK 6013443) as an investigational medicinal product (IMP) in detecting cerebral protein-plaque (amyloid beta) with positron emission tomography (PET). IMP binds to amyloidal beta protein accumulating in brain tissue already from early stages of Alzheimer's disease (AD). IMP is therefore a potential tracer to be used for detecting amyloid plaques. For each subject it is required to visit the study centre during the screening phase, on the PET imaging day and for 1 follow-up visit on the next day. A telephone call for safety follow-up will be performed 7 days after IMP administration. During the screening phase the subject's medical, neurological and surgical history, specific laboratory tests related to AD, MRI of the brain and certain neuro-psychiatric tests will be performed. Clinical safety measures (physical examinations, vital signs, electrocardiogram (ECG) and laboratory tests) will be performed on the PET imaging day before IMP injection and monitored during and after two PET imaging sessions. Clinical safety measures will be performed again on the follow-up visit next day. The results of PET imaging with IMP will be compared between probable AD patients and healthy volunteers (HV). The clinical diagnosis is based on international validated and accepted criteria and established after comprehensive clinical and neuro-psychiatric examinations
Drug: Florbetaben (BAY94-9172)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||An Open-label, Non-randomized, Multi-center Study to Optimize Image Assessment and Evaluate the Efficacy and Safety of BAY 94-9172 (ZK 6013443) Positron Emission Tomography (PET) for Detection/Exclusion of Cerebral Amyloid Beta in Patients With Probable Alzheimer's Disease Compared to Healthy Volunteers|
- Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part A Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth [ Time Frame: 90 - 110 min after investigational medical product (IMP) injection ] [ Designated as safety issue: No ]
Part A: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan which was considered a match for specificity. Standard of truth was the onsite clinical diagnosis.
Two Beta-Amyloid Plaque Load (BAPL) algorithms for assessing the normality/abnormality of beta-amyloid plaque load in the brain scans were used.
Using algorithm A (Majority Read), a brain scan of a subject with a BAPL score of "1" (without beta-amyloid plaque load) or "2" (with minor beta-amyloid plaque load) was considered normal and a BAPL score of "3" (with significant beta-amyloid plaque load) was considered abnormal.
Using algorithm B (Average), a brain scan of a subject with a BAPL score of "1" was considered normal and a brain scan with a BAPL score of "2" or "3" was considered abnormal. Algorithm B was used in Part B and in the final
- Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part B Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth. [ Time Frame: 90 - 110 min after IMP injection ] [ Designated as safety issue: No ]
Part B: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan, ie,abnormal scan (BAPL scores "2" or "3") which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan, ie,normal scan (BAPL score "1") which was considered a match for specificity.
The clinical diagnosis was established by an independent consensus panel (CP) of experts in dementia.
Two independent sets of PET data reads were performed. The first set was performed by a panel of three readers who received live, instructor-led training on the visual assessment procedure. The second set was performed by a panel of five separate readers who were trained on the visual assessment procedure with electronic media.
- Sensitivity and Specificity for All Participants Using Two Additional Imaging Windows for the Visual Assessment [ Time Frame: 45 - 60 min and 110 - 130 min after IMP injection ] [ Designated as safety issue: No ]PET scans from two additional imaging windows (45-60 min and 110-130 min) were visually assessed
- Kappa Coefficient as a Measure of Agreement Between Readers Concerning the Visual Assessment of Abnormality of the Brain Scan (Based on BAPL Score) [ Time Frame: 45-60 min, 90-110 min, 110-130 min ] [ Designated as safety issue: No ]The agreement between 3 blinded readers concerning the visual assessment of abnormality of the brain scan (based on BAPL score) was measured by the kappa coefficient. Kappa values close to 1.0 indicate a high agreement while values close to 0 indicate random agreement.
- Standard Uptake Value Ratios for Florbetaben Signal [ Time Frame: 90-110 min post injection ] [ Designated as safety issue: No ]The Standard Uptake Value Ratios for florbetaben signal in the frontal cortex, lateral temporal cortex, parietal cortex, anterior cingulate, posterior cingulate cortex, occipital cortex, and cerebellum (white matter) were determined as a quantitative measure of tracer uptake. The SUV is defined as the ratio of (1) the tissue radioactivity concentration c (in MBq/kg) at time point t, and (2) the injected activity (in MBq, extrapolated to the same time t) divided by the body weight (in kg). These SUV numbers from regions of interest were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference.)
|Study Start Date:||August 2008|
|Study Completion Date:||November 2010|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
|Experimental: Florbetaben (BAY94-9172)||
Drug: Florbetaben (BAY94-9172)
Healthy volunteers and patients with probable Alzheimer's disease receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions
Please refer to this study by its ClinicalTrials.gov identifier: NCT00750282
|United States, Arizona|
|Sun City, Arizona, United States, 85351|
|United States, California|
|Stanford, California, United States, 94305|
|United States, Connecticut|
|New Haven, Connecticut, United States, 06510|
|United States, New York|
|Bronx, New York, United States, 10461|
|New York, New York, United States, 10016|
|New York, New York, United States, 10032|
|United States, Rhode Island|
|Providence, Rhode Island, United States, 02906|
|Australia, New South Wales|
|Westmead, New South Wales, Australia, 2145|
|Australia, South Australia|
|Adelaide, South Australia, Australia, 5000|
|Heidelberg, Victoria, Australia, 3084|
|Erlangen, Bayern, Germany, 91054|
|München, Bayern, Germany, 81675|
|München, Bayern, Germany, 81377|
|Essen, Nordrhein-Westfalen, Germany, 45122|
|Jülich, Nordrhein-Westfalen, Germany, 52425|
|Münster, Nordrhein-Westfalen, Germany, 48149|
|Dresden, Sachsen, Germany, 01307|
|Leipzig, Sachsen, Germany, 04103|
|Berlin, Germany, 13125|
|Kobe, Hyogo, Japan, 650-0047|
|Kobe, Hyogo, Japan, 650-0017|
|Bunkyo-ku, Tokyo, Japan, 113-8603|
|Zürich, Switzerland, 8091|
|Study Director:||Bayer Study Director||Bayer|