Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
GSK2118436 is an orally administered, potent and selective small molecule BRAF inhibitor that is currently being developed for the treatment of BRAF mutation-positive tumors. This is an open-label, non-randomized study designed to determine the absolute bioavailability of an oral dose of 150 mg of GSK2118436 co-administered with an intravenous 50 microgram dose of [14C]GSK2118436 in subjects with BRAF mutant solid tumors. Pharmacokinetic samples will be obtained up to 72 hours post-dose. Safety assessments will be performed throughout the study. After completing all assessments, eligible subjects may transition to BRF114144, an open-label, rollover study of GSK2118436 to continue treatment.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study Medication | Experimental | GSK2118436 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2118436 | Drug | Two capsules each containing 75 mg GSK2118436, followed by a single IV dose of 50 ug (no more than 7.4 kBq or 200 nCi) [14C]GSK2118436, starting 1.75 hours after the oral dose |
| Measure | Description | Time Frame |
|---|---|---|
| The percent of absolute bioavailability (F) of GSK2118436 following single-dose oral HPMC capsule and a concomitant IV microdose | Up to 72 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum plasma concentration (Cmax) of plasma GSK2118436 and [14C]GSK2118436 | Up to 72 hours | |
| Time to Cmax (Tmax) of plasma GSK2118436 and [14C]GSK2118436 | Up to 72 hours | |
Not provided
Inclusion Criteria:
ANC >/=1.2 x 109/L Hemoglobin >/=9 g/dL Platelets >/=100 x 109/L Serum bilirubin </=1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </= 2.5 x ULN; <5 x ULN if liver metastases are present Serum creatinine </= ULN or calculated creatinine clearance >/= 60 mL/min Prothrombin time / INR and partial thromboplastin time </=1.3 x ULN Left ventricular ejection fraction >/= institutional lower limit of normal by ECHO
Exclusion Criteria:
Symptomatic Treated (surgery, radiation therapy), but not clinically and radiographically stable for a period of at least one month prior to study entry, or Asymptomatic and untreated but > 1 cm in the longest dimension Exception: Subjects with small (≤ 1 cm in the longest dimension), asymptomatic brain metastases that do not need immediate local therapy can be enrolled. Subjects on a stable dose of corticosteroids for more than one month, or those who have been off corticosteroids for at least 2 weeks can be enrolled. Subjects must also be off of enzyme-inducing anticonvulsants for more than 4 weeks;
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Tacoma | Washington | 98418 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23846776 | Background | Denton CL, Minthorn E, Carson SW, Young GC, Richards-Peterson LE, Botbyl J, Han C, Morrison RA, Blackman SC, Ouellet D. Concomitant oral and intravenous pharmacokinetics of dabrafenib, a BRAF inhibitor, in patients with BRAF V600 mutation-positive solid tumors. J Clin Pharmacol. 2013 Sep;53(9):955-61. doi: 10.1002/jcph.127. Epub 2013 Jul 12. |
| Label | URL |
|---|---|
| Results for study 113479 can be found on the GSK Clinical Study Register. | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Area under the plasma-concentration time curve (AUC) of plasma GSK2118436 and [14C]GSK2118436 |
| Up to 72 hours |
| Terminal half-life (t1/2) of plasma GSK2118436 and [14C]GSK2118436 | Up to 72 hours |
| Oral clearance (CL/F) of GSK2118436 | Up to 72 hours |
| Clearance (CL) of [14C]GSK2118436 | Up to 72 hours |
| Volume of distribution (Vd) of [14C]GSK2118436 | Up to 72 hours |
| Number of subjects with adverse events as a measure of safety and tolerability | From date of dosing until transition to rollover protocol BRF114144 (approximately 4 days) or study follow up visit if subject does not transition to BRF114144 (approximately 11 - 14 days) |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C561627 | dabrafenib |
Not provided
Not provided
Not provided