Fluticasone tablets safe for eosinophilic esophagitis
The tablet formulation of fluticasone was safe and well tolerated in adolescents and adults with eosinophilic esophagitis.
“Exploratory efficacy outcomes demonstrated improvement in histologic and endoscopic findings as well evidence of symptom improvement,” Ikuo Hirano, MD, from the department of Gastroenterology and Hepatology at Feinberg School of Medicine, Northwestern University, and colleagues wrote. “The results of this study support the continued development of APT-1011 for the treatment of EoE.”
Researchers conducted a randomized, double-blind, multicenter, phase 1b/2a study at seven medical centers in the United States to assess safety and tolerability of APT-1011, an orally disintegrating tablet formulation of fluticasone, over 8 weeks in adults and adolescents with EoE. They assigned patients to placebo (n = 8), 1.5 mg fluticasone tablets twice a day (n = 8) or 3 mg fluticasone tablets one a day (n = 8). Safety and tolerability served as the primary outcomes. Exploratory outcomes included histologic and endoscopic measures.
Investigators noted no deaths, serious or severe treatment-emergent adverse events or discontinuations due to treatment-emergent adverse events. Eighteen patients reported a total of 41 treatment-emergent adverse events; including12 patients in the fluticasone tablets group who reported 26 treatment-emergent adverse events and six patients in the placebo group who reported 15 treatment-emergent adverse events. Researchers saw a decrease in cortisol in one patient who received 1.5 mg fluticasone tablets twice a day; however, there was no evidence of adrenal insufficiency. They also saw greater reductions in esophageal eosinophil counts, Endoscopic Reference Score, patient global assessment and symptom-based EoE activity index from baseline to end of treatment in those treated with fluticasone tablets compared with placebo.
“This safety profile is particularly relevant as the dose of fluticasone studied is higher than those currently used in clinical practice for EoE with swallowed asthma formulations of fluticasone (440-880 g twice a day),” the researchers wrote. “Measurable systemic side effects of oral fluticasone propionate therapy are not expected because the absolute systemic bioavailability of orally administered fluticasone propionate is negligible (<1%) compared with inhaled fluticasone propionate (16.6%).” – by Monica Jaramillo
Disclosure: This study was funded by Adare Pharmaceuticals Inc. Hirano reports research funding from Adare, Allakos, Meritage, Celgene/Receptos, Regeneron and Shire/Takeda; and consulting fees from Adare, Allakos, Arena, AstraZeneca, Biorasi, Celgene/Receptos, Eli Lilly, EsoCap, Gossamer Bio, Regeneron and Shire/Takeda.