A Positron Emission Tomography (PET) Study to Investigate the Brain Biodistribution of 18F GSK2647544 in Healthy Subjects to Determine Its Ability to Cross the Blood-brain-barrier.

Phase 1

Terminated

• Conditions: Alzheimer's Disease
• Interventions: Drug: GSK2647544 oral; Drug: [18F]GSK2647544 IV bolus

• Registration Number: NCT01924858
• Lead Sponsor: GlaxoSmithKline

Brief Summary

This is an open label, PET study in healthy male subjects to determine if GSK2647544 is able to cross the blood-brain-barrier. The study will use GSK2647544 radiolabelled with fluorine-18 (\[18F\] GSK2647544) to determine the ratio of the concentration of the compound in tissue to that in plasma at equilibrium, expressed as the PET volume of distribution (VT). The study will consist of at least four visits; 2 screening visits, scanning day and follow-up. On Day 1 (scanning day) the subject will receive a single oral dose of GSK2647544 (100 mg) followed approximately 2 hours later by a single intravenous (IV) infusion of \[18F\]-GSK2647544 and a dynamic PET scan. Arterial and venous blood sampling will be used to determine the plasma kinetics of \[18F\]-GSK2647544 and unlabeled GSK2647544. In addition, each subject will undergo a structural magnetic resonance imaging (MRI) scan of the brain to aid in the definition of neuroanatomy. The dose of GSK2647544 was selected based on the review of the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) data obtained in the first time in human (FTIH) study.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-08-15
• Study First Submitted QC: 2013-08-15
• Study Start: 2013-08-19
• Study First Posted: 2013-08-19
• Primary Completion: 2014-03-03
• Study Completion: 2014-03-03
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-08
• Last Update Posted: 2020-10-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 4

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GSK2647544 oral and [18F]GSK2647544 IV bolus	GSK2647544 oral	All subjects will receive a single oral dose of GSK2647544 100 milligram (mg) approximately 2 hours before administration of \[18F\] GSK2647544 and a dynamic PET scan. \[18F\]-GSK2647544 will be administered to the subject as an IV bolus during the PET scan, which will be conducted for up to 120 minute post the injection of \[18F\]GSK2647544
GSK2647544 oral and [18F]GSK2647544 IV bolus	[18F]GSK2647544 IV bolus	All subjects will receive a single oral dose of GSK2647544 100 milligram (mg) approximately 2 hours before administration of \[18F\] GSK2647544 and a dynamic PET scan. \[18F\]-GSK2647544 will be administered to the subject as an IV bolus during the PET scan, which will be conducted for up to 120 minute post the injection of \[18F\]GSK2647544

Primary Outcome Measures

Name	Time	Method
Whole brain PET VT of [18F]-GSK2647544	At Day 1	The subject will be administered GSK2647544 radiolabelled with fluorine-18 (\[18F\]-GSK2647544) to determine the ratio of the concentration of the compound in tissue to that in plasma at equilibrium, expressed as the PET VT

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability assessment following oral administration of GSK2647544	Up to Day 14	The safety and tolerability assessment including adverse events assessment; clinical hematology, clinical chemistry, urinalysis and renal function tests; single 12-lead electrocardiograms (ECGs) and vital sign measurements including systolic and diastolic blood pressure (BP), pulse rate and respiratory rate.
GSK2647544 PK assessment	Pre dose and at 30minute, 1, 2, 4, 6 hours post dose on Day 1	Blood sample will be collected for PK analysis of GSK2647544 including maximum observed plasma concentration (Cmax) and time to Cmax (tmax).

Trial Locations

Locations (1)

GSK Investigational Site; 🇬🇧 London, United Kingdom