Phase II Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid.

Phase 2

Completed

• Conditions: Down Syndrome; Amyloid Beta-protein
• Interventions: Drug: Florbetaben (BAY94-9172)

• Registration Number: NCT00928304
• Lead Sponsor: Life Molecular Imaging SA

Brief Summary

To determine the sensitivity of the visual assessment of BAY94-9172 PET images in detecting cerebral β-amyloid in individuals with Down Syndrome (DS) and specificity in individuals without DS. Given that individuals with Down Syndrome develop β-amyloid pathology over the age of 40, the clinical diagnosis of Down Syndrome will serve as the standard of truth.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2009-06-24
• Study First Submitted QC: 2009-06-24
• Study First Posted: 2009-06-25
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Disposition First Submitted: 2013-05-09
• Disposition First Submitted QC: 2013-05-09
• Disposition First Posted: 2013-05-16
• Results First Submitted: 2013-12-09
• Results First Submitted QC: 2013-12-09
• Status Verified: 2014-01
• Results First Posted: 2014-01-28
• Last Update Submitted: 2014-01-29
• Last Update Posted: 2014-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 109

Inclusion Criteria

Study participants were individuals with DS and healthy volunteers (HVs).

• Main inclusion criteria for individuals without DS

  • >=21 and <= 40 years of age
  • Mini-Mental State Examination (MMSE) >= 28
  • Clinical Dementia Rating (CDR) of 0

• Main inclusion criteria for individuals with DS

  • >= 40 years of age

Exclusion Criteria

• Main exclusion criteria for both groups

  • Unstable medical or psychiatric condition, study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Florbetaben (BAY94-9172)	Florbetaben (BAY94-9172)	-

Primary Outcome Measures

Name	Time	Method
Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome	100-120 min	The primary variables are sensitivity (percentage of DS subjects positive for cerebral beta-amyloid) and specificity (percentage of healthy volunteers negative for cerebral beta-amyloid) of brain uptake of florbetaben based on the majority read of the visual assessment by three independent blinded readers of PET images obtained 100 to 120 minutes post-injection of florbetaben.

Secondary Outcome Measures

Name	Time	Method
Sensitivity Results in the Down Syndrome Age Subgroups	100 - 120 min	The majority read sensitivity (percentage of DS subjects positive for cerebral beta-amyloid by majority read) was computed for the group of DS subjects with age equal to or below the median age (DS-young) and for DS subjects with age above the median age (DS-old). The median age was 46 yrs, with 3 subjects being exactly 46 yrs old. As defined, these subjects were assigned to the DS-young group.
Quantitative Parameters Standard Uptake Value Ratio	100 - 120 min p.i.	The Standard Uptake Value Ratios for florbetaben signal in the frontal cortex, posterior cingulate, lateral temporal cortex, parietal 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.
Consistency Between Visual and Quantitative Efficacy	100 - 120 min	For a comparison of the results of the visual assessment with the quantitative assessment, descriptive Standardized Uptake Value Ratio (SUVR) statistics were computed separately for DS subjects with an abnormal/normal majority read of the PET scan (DS-PET+/DS-PET-). 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.