Relative bioavailability of fedratinib through various alternative oral administration methods in healthy adults

Abstract

AbstractFedratinib is an oral Janus kinase 2-selective inhibitor for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis; however, some patients have difficulty with oral dosing. This randomized, phase 1, open-label, 2-part crossover study evaluated the relative bioavailability, safety, tolerability, taste, and palatability of fedratinib resulting from various alternative oral administration methods in healthy adults. Participants could receive fedratinib 400 mg orally as intact capsules along with a nutritional supplement; as contents of capsules dispersed in a nutritional supplement, delivered via nasogastric tube; or as a divided dose of 200 mg orally twice daily as intact capsules with a nutritional supplement. Fifty-eight participants received treatment. Total exposure to fedratinib was similar after oral administration of intact capsules or when dispersed in a nutritional supplement (area under the plasma concentration–time curve from time 0 to the time of the last quantifiable concentration geometric mean ratio [AUC0–t GMR] [90% CI], 1.007 [0.929–1.092]). Total exposure to fedratinib was slightly reduced following nasogastric administration (AUC0–t GMR 0.850 [0.802–0.901]) and as a divided dose (AUC0–t GMR 0.836 [0.789–0.886]). No new safety signals were identified for fedratinib, and most participants found the taste and palatability acceptable when dispersed in a nutritional supplement. Overall, results suggest no clinically meaningful differences in total exposure to fedratinib between the tested oral administration methods. These findings may facilitate administration of fedratinib to patients who are intolerant of swallowing the capsule dosage form. (ClinicalTrials.gov: NCT05051553).