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The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat ascending doses of GSK2018682. The study will also provide further evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on Absolute Lymphocyte Counts (ALC).
The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat ascending doses of GSK2018682. The study will also provide further evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on Absolute Lymphocyte Counts (ALC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2018682 | Active Comparator | Active Drug |
|
| Placebo Control | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2018682 | Drug | Active Drug |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| To investigate the safety and tolerability of repeat oral doses of GSK2018682 in healthy volunteers (males and females of non-childbearing potential) | Adverse event monitoring, Laboratory parameters (haematology, clinical chemistry, urinalysis), Ophthalmic examination | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks |
| To investigate effects of repeat oral doses of GSK2018682 on heart rate and blood pressure in healthy volunteers | 12-lead ECG, Telemetry ECG, Holter ECG, Vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, body temperature), Ambulatory blood pressure monitoring | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks |
| To investigate effects of repeat oral doses of GSK2018682 on lung function in healthy volunteers | FEV1 obtained via spirometry | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks |
| To investigate the pharmacokinetics of repeat oral doses of GSK2018682 in healthy volunteers | Peak blood concentration, Time of peak blood concentration, Area under the blood concentration-time curve over the 24-hour dose interval and area under the blood concentration-time curve from time-zero extrapolated to infinite time, Accumulation ratio, Terminal half-life, Apparent oral clearance, Through concentration | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks |
| To characterize the metabolism of GSK2018682 |
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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 | ||
| GSK Investigational Site |
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| Label | URL |
|---|---|
| Results for study 114347 can be found on the GSK Clinical Study Register. | View source |
| 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 |
|---|---|---|---|
| 114347 | 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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| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000625977 | GSK2018682 |
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| Drug |
Placebo |
|
GSK2018682 bile metabolites, GSK2018682 whole blood metabolites |
| Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks |
| Evaluate the effect of repeat oral doses of GSK2018682 on lymphocytes in healthy volunteers | % Change from baseline in absolute lymphocyte counts (ALC), % Change from baseline in subsets CD3+ [CD4+ and CD8+], CD19+, CD16+/CD56+ counts, % Change from baseline in further defined functional T cell subsets (naïve, central memory, effector memory and regulatory T cells) | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks |
| To explore the PK/PD relationship between blood concentrations and changes in vital signs and ECG parameters | PK/PD model with parameters of the models will be determined that best describe the relationship between blood concentrations of GSK2018682 and vital signs and ECG parameters | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks |
| To explore the PK/PD relationship between blood concentrations of GSK2018682 and reduction in lymphocyte counts | PK/PD model with parameters of the models will be determined that best describe the relationship between blood concentrations of GSK2018682 and reduction ALC and subset counts CD3+ [CD4+ and CD8+], CD19+, CD16+/CD56+ and further defined functional T cell subsets (naïve, central memory, effector memory and regulatory T cells) | Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks |
| Adelaide |
| South Australia |
| 5000 |
| Australia |
| GSK Investigational Site | Nedlands | Western Australia | 6009 | Australia |
For additional information about this study please refer to the GSK Clinical Study Register |
| 114347 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 114347 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 114347 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 114347 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 114347 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 114347 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |