A PET Study in Healthy Volunteers
|Study Design:||Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||A Positron Emission Tomography Study in Healthy Male Subjects to Examine the Test-retest Reliability of the D2/3 Agonist Radiotracer [11C]PHNO|
- volume of distribution [ Time Frame: one year ] [ Designated as safety issue: No ]Regional volume of distribution (VT) in sub-cortical, brainstem and cerebellar regions of interest at each PET scan.
|Study Start Date:||January 2010|
|Study Completion Date:||July 2010|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Experimental: no treatment
Aripiprazole is a D2/D3 antagonist registered in the UK for use in the treatment of schizophrenia. It allows the highest clinically acceptable blockade of central D2/D3 receptors and will allow us to examine the amount of displaceable binding in the brain - a proposed reference tissue for [11C]PHNO.
examine the effects of [11C]PHNO mass carry-over and displaceable bindingDrug: Aripiprazole
A 4th scan will follow a 15mg dose of aripiprazole (a D2/D3 compound which allows the highest clinically acceptable blockade of central D2/D3 receptors)
A test-retest (TRT) investigation of [11C]PHNO in human is required to further characterise [11C]PHNO. [11C] PHNO possesses very high affinity for the D3 receptor, and therefore most clinical studies are conducted at D3 occupancies >10%. As [11C]PHNO kinetics in the target brain regions are moderately slow, considerable mass carry over may be present on a 2nd PET scan conducted on the same day. In addition there appears to be a significant displaceable binding component in the cerebellum, which, if not accounted for, will lead to a bias in the quantification of specific [11C]PHNO binding. The aim of this study is therefore to examine the effects of [11C]PHNO mass carry-over and displaceable binding in the cerebellum, on the quantification of [11C]PHNO PET data.
This will be an open label, non-randomised [11C]PHNO PET study using healthy volunteers. Each volunteer will undergo 4 [11C]PHNO PET scans:
1st and 2nd scans; TRT on the same day with a minimal gap between [11C]PHNO injections to examine the effects of PHNO mass carry over, 3rd scan >1 week later to determine the "true" TRT variability and a 4th scan will follow a 15mg dose of aripiprazole (a D2/D3 compound which allows the highest clinically acceptable blockade of central D2/D3 receptors) and will examine the amount of displaceable binding in the cerebellum, a proposed reference tissue for [11C]PHNO.
The scan data will be quantified as regional volumes of distribution (VT).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01424449
|GSK Investigational Site|
|London, United Kingdom, W12 ONN|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|