Brain Uptake of GSK1034702: a Positron Emission Tomography (PET) Scan Study

Study Overview
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Brief Summary
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GSK1034702 is being developed for improving cognitive impairment in diseases such as Alzheimer's disease and schizophrenia. This study will be done in healthy men to investigate how much of the study drug gets into the brain. This will be done using Positron Emission Tomography (PET).

Detailed Description
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This is an open label, single dose, non-randomized PET study in healthy male subjects to ascertain if GSK1034702 is crossing the blood-brain barrier to enable it to elicit a central effect. GSK1034702 has been shown in vitro to be a substrate for human Pgp, therefore the distribution of GSK1034702 into human brain could be adversely affected. This use of PET in conjunction with radioactively labelled GSK1034702 will help ascertain the role Pgp plays in limiting brain penetration in the presence and absence of a pharmacological relevant oral non labelled dose of 5 mg. Subjects will have an MRI scan to aid definition of brain anatomy, a baseline PET scan and a post-dose PET scan. For each subject the study will consist of at least three visits; screening visit, scanning day and follow-up.

Official Title
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An Open Label Positron Emission Tomography (PET) Study to Investigate Brain Penetration by [Carbonyl-11C] GSK1034702 in Healthy Subjects

Conditions
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Cognitive Disorders

Intervention / Treatment
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* Drug: GSK1034702


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy. Male between 35 and 55 years of age. Willing to use appropriate contraception method. Weight more than 50 kg. BMI within the range 19 - 29 kg/m2. Adequate blood supply to the hand. Exclusion Criteria: Abuse of drugs or alcohol. Smoker or history of regular use of tobacco- or nicotine-containing products in the past 6 months. ECG abnormality (personal or family history). Psychiatric disorder. Asthma or a history of asthma. Medical illness. Worked as a welder, metal worker or machinist. Suffers from claustrophobia or would be unable to lie still in a PET or MRI scanner for 1-2 hours. Has a cardiac pacemaker or other electrical device or ferromagnetic metal foreign bodies. Neurological disorder

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1034702<br>Single oral 5 mg dose in liquid formulation | Drug: GSK1034702<br>* Single oral 5 mg dose in liquid formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of distribution of [11C]GSK1034702 at tracer and pharmacological doses. |  | Scanning day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The kinetic rate constants at tracer and pharmacological doses. |  | Scanning day | 
| GSK1034702 PK parameters: Cmax; tmax; AUC(0-t). |  | Scanning day | 
| Safety and tolerability endpoints consisting of: AEs; 12-lead ECG; 12 lead digital Holter and lead II telemetry; vital signs; clinical laboratory evaluations. |  | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive impairment, Schizophrenia, Alzheimer's Disease, PET