Abstract
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 Cmax and AUC0–∞ 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 Cmax 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.
Key words
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Article info
Publication history
Published online: April 09, 2022
Accepted:
February 16,
2022
Identification
Copyright
© 2022 Published by Elsevier Inc.
