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This is an open-label, randomized, controlled, single center study to assess the safety, variability in exposure, and relative bioavailability of new oral formulations of SRT2104. This is a two part study and each part consists of screening (within 21 days of the first scheduled dose of SRT2104), treatment period and follow-up visit (approximately 6 days after the last dose). Part 1: Subjects will receive all four fomulations of SRT2104 and their order of their doses will be randomized. Each subject will receive one formulation as a 500 milligram (mg) dose (in the form of two 250 mg capsules or tablets) in each session given in the fasted state. Each dose will be separated by at least 6 days. Pharmacokinetic (PK) sampling will be done pre and post each scheduled dosing session. After all 4 dosing sessions, the safety and PK data will be reviewed to determine which, if any, formulation(s) will be carried forward into Part 2. The total duration will be approximately 7 weeks. Part 2: Is further divided into Part 2A, 2B and 2C of the study and are optional. After the completion of Part 1, the sponsor will decide whether to proceed with any or all of Part 2, and whether the selected formulation(s) is to be administered in the fed or fasted state for Parts 2B and 2C. For all the sub parts of Part 2 the pre and post-dose PK samples will be obtained. Part 2A: A single-dose of the selected formulation(s) from Part 1 will be administered after a standard meal to assess the effect of food on the bioavailability of SRT2104 at the 500 mg dose. The total duration will be approximately 4 weeks. Part 2B: A single alternative dose (other than 500 mg, but not to exceed 2000 mg) of the selected formulation(s) from Part 1 will be administered to assess the safety and PK profile of this dose level. The total duration will be approximately 4 weeks. Part 2C: The selected formulation(s) from Part 1 will be administered at the 500 mg dose once daily for 7 consecutive days, to assess the safety and tolerability and characterize the PK profile of repeat dosing. The total duration will be approximately 5 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Cap SRT2104 | Active Comparator | 500 mg SRT2104 (in the form of two, 250 mg capsules) will be administered as a single oral dose in the fasting state |
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| Part 1: Tab SRT2104 (slow release) | Experimental | 500 mg SRT2104 (in the form of two, 250 mg slow release tablets) will be administered as a single oral dose in the fasting state. |
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| Part 1: Tab SRT2104 (intermediate release) | Experimental | 500 mg SRT2104 (in the form of two, 250 mg intermediate release tablets) will be administered as a single oral dose in the fasting state. |
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| Part 1: Tab SRT2104 (fast release) | Experimental | 500 mg SRT2104 (in the form of two, 250 mg fast release tablets) will be administered as a single oral dose in the fasting state. |
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| Part 2A: SRT2104 500 mg single-dose | Experimental | 500 mg SRT2104 (formulation selected from Part 1) will be administered as a single oral dose in the fed state. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cap SRT2104 | Drug | Micronized free base in a 250 mg SRT2104 (active equivalents) capsule |
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| Measure | Description | Time Frame |
|---|---|---|
| Measure of variability in exposure-CVw | The variability in exposure of SRT2104 will be assessed by calculating the within subject coefficient of variation (CVw). | Part 1: Days 1, 8, 15 and 22; Parts 2A and 2B: Day 1; Part 2C: Days 1 to 7. Pre dose and post-dose at 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after each scheduled dosing session. |
| Measure of relative bioavailability-AUC | Relative bioavailability of SRT2104 will be assessed by evaluating area under the curve (AUC). | Part 1: Days 1, 8, 15 and 22; Parts 2A and 2B: Day 1; Part 2C: Days 1 to 7. Pre dose and post-dose at 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after each scheduled dosing session. |
| Measure of relative bioavailability-Cmax | Relative bioavailability of SRT2104 will be assessed by measuring maximum observed plasma concentration (Cmax). | Part 1: Days 1, 8, 15 and 22; Parts 2A and 2B: Day 1; Part 2C: Days 1 to 7. Pre dose and post-dose at 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after each scheduled dosing session. |
| Measure of relative bioavailability-Tmax | Relative bioavailability of SRT2104 will be assessed by measuring the time to reach maximum observed plasma concentration (Tmax). | Part 1: Days 1, 8, 15 and 22; Parts 2A and 2B: Day 1; Part 2C: Days 1 to 7. Pre dose and post-dose at 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after each scheduled dosing session. |
| Safety of SRT2104 as assessed by number of subjects with adverse events (AE)s | Safety parameter will include recording number of AEs, throughout the study. | Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. |
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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 | Baltimore | Maryland | 21225 | United States |
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| Label | URL |
|---|---|
| Results for study 117041 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 |
|---|---|---|---|
| 117041 | Annotated Case Report Form | 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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| Part 2B: SRT2104 single alternative dose | Experimental | An alternative dose (other than 500 mg, but not to exceed 2000 mg) of SRT2104 (formulation selected from Part 1) will be administered as a single oral dose. |
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| Part 2C: SRT2104 500 mg daily for 7 days | Experimental | 500 mg SRT2104 (formulation selected from Part 1) will be administered daily for 7 days. |
|
| Tab SRT2104 slow release | Drug | New 250 mg SRT2104 mesylate salt slow release tablet |
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| Tab SRT2104 intermediate release | Drug | New 250 mg SRT2104 mesylate salt intermediate release tablet |
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| Tab SRT2104 fast release | Drug | New 250 mg SRT2104 mesylate salt fast release tablet |
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| Selected formulations of SRT2104 from Part 1 | Drug | SRT2104 500 mg of selected formulation(s) from Part 1 in single-dose or daily for 7 days |
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| Selected formulations of SRT2104 from Part 1 single alternative dose | Drug | SRT2104 single alternative dose (other than 500 mg, but not to exceed 2000 mg) of selected formulation(s) from Part 1 |
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| Safety of SRT2104 as assessed by intensity of AEs | Safety parameter will include recording of intensity of AEs, throughout the study. | Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. |
| Safety of SRT2104 as assessed by type of AEs | Safety parameter will include recording of type of AEs, throughout the study. | Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. |
| Safety of SRT2104 as assessed by change from Baseline in heart rate | Safety will be assessed by recording heart rate at Baseline and at end of the study. | Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. |
| Safety of SRT2104 as assessed by change from Baseline in blood pressure | Safety will be assessed by recording blood pressure at Baseline and at end of the study. | Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. |
| Safety of SRT2104 as assessed by change from Baseline in temperature | Safety will be assessed by recording temperature at Baseline and at end of the study. | Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. |
| Safety of SRT2104 as assessed by change from Baseline in ECG readings | Safety will be assessed by recording the electrocardiogram (ECG) readings at Baseline and at end of the study. | Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. |
| Safety of SRT2104 as assessed by change from Baseline in clinical laboratory parameters | Clinical laboratory parameters will include hematology, clinical chemistry and electrolytes, serology, coagulation and urinalysis. Safety will be assessed by evaluating the clinical laboratory parameter readings at Baseline and at end of the study. | Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. |
For additional information about this study please refer to the GSK Clinical Study Register |
| 117041 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117041 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117041 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117041 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117041 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117041 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ID | Term |
|---|---|
| D011565 | Psoriasis |
| ID | Term |
|---|---|
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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