A Phase I, Open-label, Randomized, Crossover Study of the Relative Bioavailability of Capsule and Granule Formulations of Selumetinib.

Purpose: Selumetinib (ARRY-142886) is an oral, potent, and highly selective allosteric mitogen-activated protein kinase kinase 1/2 inhibitor approved for the treatment of pediatric patients (≥2 years of age) with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. This Phase I crossover study (NCT03649165) evaluated the pharmacokinetic properties and palatability of a new granule formulation of selumetinib.

Methods: Healthy volunteers were randomized to 1 of 2 sequences; selumetinib granule (25 mg) followed by selumetinib capsules (50 mg [2 × 25 mg]) and vice versa. The primary end point was the pharmacokinetic properties of the 2 formulations. Secondary end points included safety and tolerability of single selumetinib doses and palatability of the granule formulation.

Findings: Of the 24 enrolled volunteers (mean age, 33.2 years; range 23-44 years), all were male and 20 (83%) were Black/African American. Under fasted conditions for the granule versus capsule, geometric mean ratios for the dose-normalized C and AUC were 0.654 (90% CI, 0.581-0.736) and 0.865 (90% CI, 0.811-0.922), respectively. Absorption of selumetinib was similar between granule and capsule formulation, with a median time to C of 1.73 hours and 1.14 hours, respectively. Adverse event incidence was low (n = 6 in both groups), and most events were mild. Palatability was acceptable, with volunteers indicating that they would take the granule formulation again.

Implications: These findings support further research into the selumetinib granule formulation, with the aim of producing an alternative formulation for younger children or patients unable to swallow capsules.

Clinicaltrials: gov identifier: NCT03649165.