Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Melanoma

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Lipid Regulating Agents

Antineoplastic Agents

Bone Density Conservation Agents

Midazolam

Rosuvastatin Calcium

Dabrafenib

Calcium

Calcium, Dietary

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Enzyme Inhibitors

Protein Kinase Inhibitors

On Day 1 subjects will simultaneously receive single dose of Rosuvastatin 10 mg tablet and Midazolam 3 mg syrup administered orally in the morning.

Commercially available Rosuvastatin 10 mg tablets will be supplied. Single oral dose of Rosuvastatin 10 mg will be administered on Day 1, 8 and 22

Rosuvastatin10 mg tablet

Commercially available Midazolam syrup will be supplied.Single oral dose of Midazolam 3 mg syrup will be administered on Days 1, 8 and 22

Midazolam 3 mg syrup

Dabrafenib 75mg will be supplied in the form of capsules. Oral dose Dabrafenib 150 mg (2 x 75 mg) BID will be administered at 12 h apart on Days 8 through 22 and 150 mg (2 x 75 mg) OD on Day 23.

Dabrafenib 75 mg capsule

GSK Clinical Trials

This is an open-label, multi-center, fixed sequence study in subjects with BRAF V600 mutation positive tumors. Subjects will receive single oral doses of 10 milligram (mg) of rosuvastatin and 3 mg of midazolam in the morning of Day 1 (alone), Day 8 (with first dose of dabrafenib 150 mg), and Day 22 (during repeat dose dabrafenib 150 mg twice daily \[BID\]). Dabrafenib 150 mg BID will be administered from Day 8 to Day 23. Blood samples for PK analysis will be obtained over 32 hours post-dose on Day 1, Day 8, and Day 22. The last dose of dabrafenib will be taken in the morning of Day 23 and the last blood sample in the evening of Day 23. Subjects will be considered to have completed the study once the 32 hour PK sample has been collected on Day 23. Once they have completed the study, eligible subjects may have the option to enter study BRF114144, an open-label roll-over study of dabrafenib (no follow-up visit required) and continue receiving dabrafenib.

Effects of Dabrafenib on the Single Dose Pharmacokinetics (PK) of Rosuvastatin and Midazolam

An Open-label Phase 1 Study to Evaluate the Effects of Dabrafenib (GSK2118436) on the Single Dose Pharmacokinetics of an OATP1B1/1B3 Substrate and of a CYP3A4 Substrate in Subjects With BRAF V600 Mutation Positive Tumors

Blood samples will be collected for assessment of PK parameters including maximum observed concentration (Cmax), time to Cmax (tmax), and area under the concentration-time curve from pre-dose extrapolated to infinite time (AUC\[0-infinity\])

Blood samples will be collected for assessment of PK parameters including area under the concentration-time curve to time of last measurable concentration (AUC\[0-t\]), area under the concentration-time curve from time zero to a time point determined from the data (AUC (partial), terminal phase half-life (t1/2)

Blood samples will be collected for assessment of concentration of dabrafenib and its metabolites

AE is defined as Any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis)

Vital sign measurements will include systolic and diastolic blood pressure, respiratory rate, pulse rate and pulse oximetry Vital signs should be measured after sitting in a semi-supine position for at least 5 min.

Cardiac assessments include 12-lead Electrocardiogram (ECG)

Spots Global Cancer Trial Database for rosuvastatin10 mg tablet