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A Study to Examine the Pharmacodynamic Effects of GSK1034702 on Neurophysiological Biomarkers of Cognition in Nicotine Abstained Otherwise Healthy Smokers

Phase 1
Completed
Conditions
Mental Disorders
Interventions
Drug: Drug
Registration Number
NCT01371799
Lead Sponsor
GlaxoSmithKline
Brief Summary

This will be a double blind, randomised, placebo controlled, cross over study in which up to 20 otherwise healthy male nicotine abstinent smokers will be tested following 3 acute treatment conditions (placebo, 4 and 8mg of GSK1034702). Each subject will undergo screening assessments within 30 days prior to administration of the first dose of study medication. There will be 3 treatment sessions and dosing will be separated by a minimum 1 week washout period. There will be two testing days (day 1 and day 2) per treatment session. On each treatment session subjects will be admitted on day 1. On day 1, subjects will be administered placebo and approximately 3 hours later, there will be a Baseline EEG/ERP recording, neuropsychological (Cogstate battery) testing and mood/craving/dependence questionnaire assessments . Subjects will be allowed to smoke until approximately midnight on day 1. On day 2, subjects will undergo a pre-drug neuropsychological (Cogstate battery) testing and questionnaire assessments of mood/craving. This will be conducted approximately 1 hour prior to dosing. Subjects will be randomized to one of six treatment sequences. Post dose EEG/ERP recording, neuropsychological (Cogstate battery) testing and mood/craving measurements will be conducted between 3 and 6 hours post treatment to coincide with peak pharmacokinetic effects. This testing will be performed approximately at 12pm following at least 12hrs of nicotine abstinence. Blood samples will be collected at baseline (pre-drug) and following drug administration to quantify exposure levels.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
9
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboDrugPlacebo
Study drug at 4mgDrugGSK1034702 at 4mg
Study drug at 8mgDrugGSK1034702 at 8mg
Primary Outcome Measures
NameTimeMethod
Measures will include changes in cognition measures of specific biomarkers12 months

To investigate the effects of GSK1034702 on the mismatch negativity neurophysiologic marker of cognition.

Secondary Outcome Measures
NameTimeMethod
Measures will include changes in the neurophysiologic markers of cognition12 Months

To investigate the effects of GSK1034702 on other neurophysiologic markers of cognition including, P50 suppression, P300, PPI and synchronized oscillations.

Measures of changes in cognition biomarkers vs. the stduy drug12 months

To investigate the relationship between changes in the above neurophysiologic markers of cognitive function and drug exposure

Measures of difference between the tests in cogstate and the drug levels at different concentrations To investigate the relationship between changes in Cogstate behavioural task performance and drug exposure12 months

To investigate the relationship between changes in Cogstate behavioural task performance and drug exposure

Safety measures and PK parameters and PK parameters will be measures, Vital signs, BP. To obtain further safety and PK information following oral administration of GSK1034702 to healthy subjects12 months

To obtain further safety and PK information following oral administration of GSK1034702 to healthy subjects

Measures of cogstate tests of attention in tests mentioned To investigate the effects of GSK1034702 on Cogstate neuropsychologic tests of attention, working memory, learning and executive function12 months

To investigate the effects of GSK1034702 on Cogstate neuropsychologic tests of attention, working memory, learning and executive function

Measures in modd/craving To investigate changes in mood/craving in the nicotine "on" state (baseline), following nicotine abstinence and following treatment12 months

To investigate changes in mood/craving in the nicotine "on" state (baseline), following nicotine abstinence and following treatment

Trial Locations

Locations (1)

GSK Investigational Site

🇬🇧

Cambridge, United Kingdom

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