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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study drug at 4mg | Experimental | GSK1034702 at 4mg |
|
| Study drug at 8mg | Experimental | GSK1034702 at 8mg |
|
| Placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Drug | Drug | Placebo |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Measures will include changes in cognition measures of specific biomarkers | To investigate the effects of GSK1034702 on the mismatch negativity neurophysiologic marker of cognition. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Measures will include changes in the neurophysiologic markers of cognition | To investigate the effects of GSK1034702 on other neurophysiologic markers of cognition including, P50 suppression, P300, PPI and synchronized oscillations. | 12 Months |
| Measures of changes in cognition biomarkers vs. the stduy drug |
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Inclusion Criteria A subject will be eligible for inclusion in this study only if all of the following criteria apply:
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cambridge | CB2 2GG | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22932339 | Background | Nathan PJ, Watson J, Lund J, Davies CH, Peters G, Dodds CM, Swirski B, Lawrence P, Bentley GD, O'Neill BV, Robertson J, Watson S, Jones GA, Maruff P, Croft RJ, Laruelle M, Bullmore ET. The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction. Int J Neuropsychopharmacol. 2013 May;16(4):721-31. doi: 10.1017/S1461145712000752. Epub 2012 Aug 29. | |
| 23067311 |
| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 113746 | Individual Participant Data Set | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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| Drug |
| Drug |
4mg and 8mg Study drug |
|
To investigate the relationship between changes in the above neurophysiologic markers of cognitive function and drug exposure |
| 12 months |
| 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 function | To investigate the effects of GSK1034702 on Cogstate neuropsychologic tests of attention, working memory, learning and executive function | 12 months |
| 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 exposure | To investigate the relationship between changes in Cogstate behavioural task performance and drug exposure | 12 months |
| 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 subjects | To obtain further safety and PK information following oral administration of GSK1034702 to healthy subjects | 12 months |
| Measures in modd/craving To investigate changes in mood/craving in the nicotine "on" state (baseline), following nicotine abstinence and following treatment | To investigate changes in mood/craving in the nicotine "on" state (baseline), following nicotine abstinence and following treatment | 12 months |
| Background |
| te Beek ET, Hay JL, Bullman JN, Burgess C, Nahon KJ, Klaassen ES, Gray FA, van Gerven JM. Pharmacokinetics and central nervous system effects of the novel dual NK1 /NK3 receptor antagonist GSK1144814 in alcohol-intoxicated volunteers. Br J Clin Pharmacol. 2013 May;75(5):1328-39. doi: 10.1111/bcp.12004. |
| Results for study 113746 can be found on the GSK Clinical Study Register. | View source |
For additional information about this study please refer to the GSK Clinical Study Register |
| 113746 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113746 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113746 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113746 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113746 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
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| ID | Term |
|---|---|
| D004364 | Pharmaceutical Preparations |
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