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
Condition: Alzheimer Disease; Amyloid Beta-Protein
MeSH terms: Alzheimer Disease; Amyloidosis
Intervention: Florbetaben (BAY94-9172)
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 422.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: Alzheimer Disease; Amyloid beta-Protein

Summary:

      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
    

Eligibility criteria:

        Inclusion Criteria:

          -  Each subject / Healthy volunteer (HV) who meets the following criteria will be
             eligible for enrollment into the study:

               -  Is a man or woman and is > 55 of age, whereby females must be without
                  childbearing potential (confirmed by either: age >/= 60; or history of
                  hysterectomy, or last spontaneous bleeding at least 2 years prior to the study
                  start)

               -  Has at least 6 years of education

               -  Is able to provide informed consent, understand the information provided on the
                  purpose and conduct of the trial and to comply with study procedures

               -  Possesses a general health that permits adequate compliance with all study
                  procedures

               -  The subject, or the subject and caregiver (for probable AD patients) will be
                  compliant and have a high probability of completing the study

               -  Informed consent has been signed and dated (with time) by the subject and/or the
                  subject's caregiver (for probable AD patients)

          -  Inclusion criteria for HV only:

               -  Has no evidence of cognitive impairment

               -  Has MRI brain scan that has been judged as "normal" (age- appropriate)

          -  Inclusion criteria for patients with AD only:

               -  Presents with positive assessment for dementia of Alzheimer's type

               -  Does not fulfill the criteria Dementia with Lewy Bodies (DLB) or Vascular
                  Dementia (VaD)

               -  MRI brain scan findings that do not reveal changes indicative of stroke and/or
                  generalized cerebrovascular disease

               -  Has a caregiver that is willing and able to attend all study visits and perform
                  the psychometric tests requiring the presence of a caregiver

        Exclusion Criteria:

          -  Has any contraindication to MRI examination scan

          -  Is scheduled for surgery and/or another invasive procedure within the time period of
             up to 24 hours following IMP application

          -  Is allergic to the IMP or any of its constituents and/or has a history of severe
             allergic reactions to drugs or allergens (e.g. patients / volunteers with allergic
             asthma)

          -  is critically ill and/or medically unstable and whose clinical course during the
             observation period is unpredictable

          -  Has a history of exposure to any radiation >15 milli Sieverts (mSv)/year (e.g.
             occupational or radiation therapy)

          -  Is receiving drug therapy or other treatment that is known to lead to greatly
             fluctuating values of the hematological or chemical laboratory parameters or to severe
             side effects (e.g. chemotherapy)

          -  Has been previously enrolled in this study or participated in a clinical study
             involving an investigational pharmaceutical product within 30 days prior to screening,
             and/or any radiopharmaceutical

          -  Has a brain tumor or other intracranial lesion, a disturbance of cerebro-spinal fluid
             (CSF) circulation (e.g., normal pressure hydrocephalus) and/or a history of head
             trauma or brain surgery

          -  Has an inflammatory or infectious central nervous system (CNS) disease, e.g. multiple
             sclerosis, HIV, syphilis, or Creutzfeldt-Jacob disease

          -  Has a history, physical, laboratory or imaging findings indicative of a neurological
             or psychiatric illness

          -  Has another disease that can cause disturbance of brain function (e.g. vitamin B12 or
             folic acid deficiency, disturbed thyroid function)

          -  Has a history of alcohol or drug abuse

          -  Has history of severe persistent depression