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This is an open-label, randomized, single-dose, 2-treatment, 2-period, 2-way crossover study with incomplete wash-out in subjects with solid tumors to determine the relative bioavailability of test formulation with lower dimethyl sulfoxide (DMSO) content as compared with standard reference formulation trametinib.
Approximately 18 subjects will be randomized to receive either a single dose of Treatment A (standard target DMSO content [theoretical 11.3%] formulation of GSK1120212B) or a single dose of Treatment B (lower DMSO Content [approximately 9.5%] formulation of GSK1120212B) followed by a 7 day incomplete wash-out period, then a single dose of the other treatment.
Administration of the dose under fasted conditions in Periods 1 and 2 will be only on Day 1 followed by 7 days of serial blood sampling for PK analysis of plasma trametinib. Safety assessments, including assessment of AEs, clinical laboratory (hematology and clinical chemistry) and vital signs, will be made throughout the study.
After a subject completes the study, he or she may be eligible to enter study MEK114375, an open-label rollover study of trametinib (no wash-out period or follow-up visit required) and continue receiving trametinib. For those subjects who wish to discontinue or complete the current study and choose not enter the rollover study, a follow-up visit should be performed within 21 days after receiving the last dose of study treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A: GSK1120212B (Standard DMSO content) | Experimental | Subjects will receive Treatment A in Period 1 or 2 as single oral dose on Day 1 of Period 1 or 2 in fasting condition with water. |
|
| Treatment B: GSK1120212B (Lower DMSO content) | Experimental | Subjects will receive Treatment B in Period 1 or 2 as single oral dose on Day 1 of Period 1 or 2 in fasting condition with water. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK1120212B (Standard DMSO content) | Drug | Each tablet contains GSK1120212B equivalent to 2 mg of GSK1120212 as drug substance. The coated tablets have a standard DMSO content of theoretical 11.3%. |
| Measure | Description | Time Frame |
|---|---|---|
| Corrected Cmax of GSK1120212B | Pharmacokinetic data will include corrected maximum plasma concentration (Cmax) of GSK1120212B. Comparison of Cmax will enable to determine the relative bioavailability of the test formulation with lower DMSO content (Treatment B) and the standard reference formulation (Treatment A). Period 2 PK parameters will be corrected for residual concentrations from Period 1 (based on individual estimates of t1/2) to remove the carry-over effect. | Period 1 and 2: Day 1 pre-dose within 15 minutes (mins) of planned study treatment administration (serves as the 168-hour [hr] sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs ( |
| Corrected AUC(0-t) and AUC(0-inf) of GSK1120212B | Pharmacokinetic data will include corrected area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) and AUC from zero to infinity (AUC(0-inf)) of GSK1120212B. Period 2 PK parameters will be corrected for residual concentrations from Period 1 (based on individual estimates of t1/2) to remove the carry-over effect. | Period 1 and 2: Day 1 pre-dose within 15 mins of planned study treatment administration (serves as the 168-hr sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (Day 3), 72 hrs ( |
| Corrected tmax of GSK1120212B | Pharmacokinetic data will include corrected time of occurrence of Cmax (tmax) of GSK1120212B. Period 2 PK parameters will be corrected for residual concentrations from Period 1 (based on individual estimates of t1/2) to remove the carry-over effect. | Period 1 and 2: Day 1 pre-dose within 15 mins of planned study treatment administration (serves as the 168-hr sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (Day 3), 72 hrs ( |
| Measure | Description | Time Frame |
|---|---|---|
| Uncorrected Cmax of GSK1120212B | Pharmacokinetic data will include uncorrected Cmax of GSK1120212B. | For Period 1 and 2 on Day 1: pre-dose within 15 mins of planned study treatment administration (serves as the 168-hr sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (Day 3), 72 |
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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 | Goodyear | Arizona | 85338 | United States | ||
| GSK Investigational Site |
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| Label | URL |
|---|---|
| Results for study 114656 can be found on the GSK Clinical Study Register. | View source |
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| GSK1120212B (Lower DMSO content) | Drug | Each tablet contains GSK1120212B equivalent to 2 mg of GSK1120212 as drug substance. The coated tablets have a lower DMSO content approximately 9.5%. |
|
| Uncorrected AUC(0-t), AUC(0-inf) and AUC(0-24) of GSK1120212B | Pharmacokinetic data will include uncorrected AUC(0-t), AUC(0-inf) and AUC from zero to 24 hrs AUC(0-24) of GSK1120212B. | For Period 1 and 2 on Day 1: pre-dose within 15 mins of planned study treatment administration (serves as the 168-hr sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (Day 3), 72 |
| Pre-dose concentration (C0) of GSK1120212B | Pharmacokinetic data will include uncorrected C0 of GSK1120212B in Period 2 | Period 2: Day 1 pre-dose within 15 minutes (mins) of planned study treatment administration (serves as the 168-hour [hr] sample for Period 1. |
| Elimination half life (t½) of GSK1120212B | Pharmacokinetic data will include t1/2 of GSK1120212B. | Period 1 and 2: Day 1 pre-dose within 15 mins of planned study treatment administration (serves as the 168-hr sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (Day 3), 72 hrs ( |
| Safety of GSK1120212B as assessed by changes in vital signs measurements | Safety data will include measurements of vital signs (blood pressure, pulse rate and temperature) at Baseline and end of the study. | Through Day 36. |
| Safety of GSK1120212B as assessed by changes in clinical laboratory tests | Safety data will include assessments of clinical laboratory tests (hematology, clinical chemistry, coagulation and at Baseline and end of the study. | Through Day 36. |
| Safety of GSK1120212B as assessed by number of subjects with adverse events (AE)s | Safety data will include recording of number of subjects with AEs. | Through Day 36 |
| Scottsdale |
| Arizona |
| 85259 |
| United States |
| GSK Investigational Site | Sarasota | Florida | 34232 | United States |
| GSK Investigational Site | Nashville | Tennessee | 37203 | United States |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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