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The current study will examine the safety, tolerability, plasma pharmacokinetics (PK), and plasma pharmacodynamics (PD) of single-doses of GSK2647544.The study will be conducted as a randomized, single-blind, placebo controlled, 4-way crossover single oral ascending dose design in 2 independent cohorts, eight healthy male subjects in each of the cohorts. Each potential subject will undergo Screening visit, Treatment Phase and Follow-up visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2647544 | Experimental | The starting dose of GSK2647544 is 0.5 mg. The escalating doses to be administered will be determined based on study results from previous dose (s). |
|
| Placebo | Placebo Comparator | Matching placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2647544 | Drug | Capsules containing 0.5mg to 50mg of GSK2647544. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of GSK2647544 as assessed by number of subjects with adverse events (AE)s | Safety and tolerability parameters will include recording of AEs | 5 days in each of the 4 dosing session |
| Safety and tolerability of GSK2647544 as assessed by change from Baseline in laboratory values | Safety and tolerability parameters will include laboratory (haematology, clinical chemistry, urinalysis) values at Screening, Day -1, Day 3 and Follow-up (7-14 days post-last dose) | 5 days in each of the 4 dosing session |
| Safety and tolerability of GSK2647544 as assessed by change from Baseline in ECG readings | Safety and tolerability parameter will include the electrocardiogram (ECG) readings at Screening, Day -1, Day 1, Day 2, Day 3 and Follow-up (7-14 days post-last dose) | 5 days in each of the 4 dosing session |
| Safety and tolerability of GSK2647544 as assessed by change from Baseline in Telemetry ECG parameters | Safety and tolerability parameter will include the Telemetry ECG readings from 30 minutes pre-dosing till 48 hours post-dosing | 3 Days in each of the 4 dosing session |
| Safety and tolerability of GSK2647544 as assessed by change from Baseline in vital signs | Vital signs measurement include systolic and diastolic blood pressure and pulse rate at Screening, Day -1, Day 1, Day 2, Day 3, Day 4 and Follow-up (7-14 days post-last dose) | 5 days in each of the 4 dosing session |
| Safety and tolerability of GSK2647544 as assessed by using the Columbia Suicide Severity Rating Scale (C-SSRS) |
| Measure | Description | Time Frame |
|---|---|---|
| Peak plasma concentration (Cmax) of GSK2647544 | To assess PK profile of GSK2647544, Cmax of GSK2647544 will be measured | 4 Days in each of the 4 dosing session |
| Time of peak plasma concentration (tmax) of GSK2647544 |
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Inclusion Criteria:
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 | Randwick | New South Wales | 2031 | Australia |
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| Label | URL |
|---|---|
| Results for study 116698 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 116698 | Clinical Study Report | 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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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000615596 | GSK2647544 |
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| Placebo |
| Drug |
Matching placebo capsules. |
|
C-SSRS will be measured at Screening, Day -1, Day 1 (conducted prior to discharge) and Follow-up (7-14 days post-last dose)
| 5 days in each of the 4 dosing session |
To assess PK profile of GSK2647544 tmax of GSK2647544 will be measured
| 4 Days in each of the 4 dosing session |
| Area under the time concentration curve (AUC) of GSK2647544 | To assess PK profile of GSK2647544 AUC of GSK2647544 will be measured | 4 Days in each of the 4 dosing session |
| Terminal half-life (t½ ) of GSK2647544 | To assess PK profile of GSK2647544 t½ of GSK2647544 will be measured | 4 Days in each of the 4 dosing session |
| Apparent oral clearance (CL/F) of GSK2647544 | To assess PK profile of GSK2647544 CL/F of GSK2647544 will be measured | 4 Days in each of the 4 dosing session |
| Predose plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and postdose Lp-PLA2 activity | It will be measured at Day 1, Day 2, Day 3, Day 4 and Day 5 | 5 Days in each of the 4 dosing session |
For additional information about this study please refer to the GSK Clinical Study Register |
| 116698 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116698 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116698 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116698 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116698 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116698 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |