Relative bioavailability of pediatric oral solution and tablet formulations of trametinib in adult patients with solid tumors. Issue 4 (27th October 2014)

• Record Type: Journal Article
• Authors: Cox, Donna S.; Allred, Alicia; Zhou, YanYan; Infante, Jeffrey R.; Gordon, Michael S.; Bendell, Johanna; Jones, Suzanne; Burris, Howard; Orford, Keith
• Is Part Of: Clinical pharmacology in drug development. Volume 4:Issue 4(2015:Jul./Aug.)
• Page Start: 287
• Page End: 294
• Publication Date: 2014-10-27
• Subjects: Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.152
• Languages: English
• ISSNs: 2160-7648

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="cpdd152-sec-0001" sec-type="section"> <p>Trametinib (Mekinist®) is a selective inhibitor of mitogen‐activated protein kinase kinase (MEK) approved in the United States as a single agent and in combination with dabrafenib (Tafinlar®) for treatment of patients with unresectable or metastatic melanoma with a positive BRAF V600E/V600K mutation for which a pediatric oral solution formulation is being developed. This open‐label, two‐period, two‐treatment, randomized, crossover study assessed the relative bioavailability of the trametinib pediatric oral solution compared to the tablet formulation after a single‐dose administration to adult patients with solid tumors. Primary pharmacokinetic endpoints derived from standard non‐compartmental methods were AUC<sub>0–inf</sub>, AUC<sub>0–t</sub>, and C<sub>max</sub>. As expected, C<sub>max</sub> was higher and T<sub>max</sub> earlier for the pediatric oral solution compared to the tablet formulation. Administration of the trametinib pediatric oral solution resulted in a 12%, 10%, 18%, and 71% higher AUC<sub>0–inf</sub>, AUC<sub>0–last</sub>, AUC<sub>0–24</sub>, and C<sub>max</sub>, respectively, as compared to the tablet formulation. Safety results were aligned with the known safety profile of trametinib. No serious or non‐serious adverse events resulted in study drug withdrawal. Palatability of the pediatric oral solution was evaluated and found to be acceptable to most adult patients, but may differ in the pediatric population.</p> </sec> </abstract>