Clinical trial NCT00937846: Brain Uptake of GSK1034702: a Positron Emission Tomography (PET) Scan Study
Official title: An Open Label Positron Emission Tomography (PET) Study to Investigate Brain Penetration by [Carbonyl-11C] GSK1034702 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cognitive Disorders
Keywords: Cognitive impairment
Schizophrenia
Alzheimer's Disease
PET
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-07-13
Enrollment: 4
Sex: MALE
Minimum age (years): 35
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Volume of distribution of [11C]GSK1034702 at tracer and pharmacological doses.
timeFrame: Scanning day
Secondary outcomes:
measure: The kinetic rate constants at tracer and pharmacological doses.
timeFrame: Scanning day
measure: GSK1034702 PK parameters: Cmax; tmax; AUC(0-t).
timeFrame: Scanning day
measure: Safety and tolerability endpoints consisting of: AEs; 12-lead ECG; 12 lead digital Holter and lead II telemetry; vital signs; clinical laboratory evaluations.
timeFrame: 2 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Ridler K, Cunningham V, Huiban M, Martarello L, Pampols-Maso S, Passchier J, Gunn RN, Searle G, Abi-Dargham A, Slifstein M, Watson J, Laruelle M, Rabiner EA. An evaluation of the brain distribution of [(11)C]GSK1034702, a muscarinic-1 (M 1) positive allosteric modulator in the living human brain using positron emission tomography. EJNMMI Res. 2014 Dec;4(1):66. doi: 10.1186/s13550-014-0066-y. Epub 2014 Dec 5.