NCT01072175 · OUTCOME

Part B: AUC [0-tau] of Dabrafenib (DAB) and Its Metabolite in Combination With Trametinib

Investigate Safety, Pharmacokinetics and Pharmacodynamics of GSK2118436 & GSK1120212 · Source last updated 2019-07-05

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure: GEOMETRIC_MEAN
Unit: ng*hr/mL
Interval / dispersion: 95% Confidence Interval
Time frame: Day 15 and Day 21

What was measured

Area under the concentration-time curve from time zero (predose) until the last time of quantifiable concentration (AUC \[0-tau\]) was assessed. Blood samples for PK analysis of dabrafenib and its the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration.

Analysis population: PK Population. Only those participants who were available at the indicated time point were analyzed.

Groups in this outcome

Part B: Dabrafenib 75 mg + Trametinib 1 mg

Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors received dabrafenib 75 mg gelatin capsules BID and trametinib 1 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available pharmacokinetic (PK), safety, and other data from the first 4 evaluable participants, and additional participants were enrolled based on dose-limiting toxicities (DLTs) occurring during the first 3 weeks of treatment.

Part B: Dabrafenib 150 mg + Trametinib 1 mg

Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors and participants who had salivary ductal cancer received dabrafenib 150 mg gelatin capsules BID and trametinib 1 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available PK, safety, and other data from the first 4 evaluable participants and additional participants were enrolled based on DLTs occurring during the first 3 weeks of treatment.

Part B: Dabrafenib 150 mg + Trametinib 1.5 mg

Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors received dabrafenib 150 mg gelatin capsules BID and trametinib 1.5 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available PK, safety, and other data from the first 4 evaluable participants, and additional participants were enrolled based on DLTs occurring during the first 3 weeks of treatment.

Part B: Dabrafenib 150 mg + Trametinib 2 mg

Melanoma BRAF-positive participants who received prior treatment with BRAF inhibitors and participants who had colorectal cancer and BRAFi naïve melanoma received dabrafenib 150 mg gelatin capsules BID and trametinib 2 mg tablets QD as continuous daily dosing. Dose escalation did not proceed beyond these doses of dabrafenib and trametinib.

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.