Randomised clinical trial: the safety and tolerability of fluticasone propionate orally disintegrating tablets versus placebo for eosinophilic oesophagitis.

Abstract

BACKGROUND:

APT-1011, a fluticasone propionate orally disintegrating tablet formulation, is under investigation for the treatment of eosinophilic oesophagitis (EoE).

AIMS:

To evaluate the safety and tolerability of APT-1011 administered to patients with EoE and to assess the effect on clinical symptoms of EoE, endoscopic appearance and oesophageal eosinophilia.

METHODS:

A randomised, double-blind, placebo-controlled, multicentre, phase 1b/2a study was conducted at seven medical centres in the US to evaluate the safety and tolerability of APT-1011 over 8 weeks in adults and adolescents with EoE. Participants were randomised to placebo (n = 8), 1.5 mg APT-1011 BID (n = 8) or 3.0 mg APT-1011 QD (n = 8). Safety and tolerability were assessed as the primary outcome; histologic and endoscopic measures were assessed as exploratory outcomes.

RESULTS:

There were no deaths, serious treatment-emergent adverse events (TEAEs), severe TEAEs or discontinuations from the study related to a TEAE. In one participant randomised to 1.5 mg APT-1011 BID, a reduction in cortisol was observed, but without evidence of adrenal insufficiency. Compared with placebo, treatment with APT-1011 resulted in greater reductions in oesophageal eosinophil counts, EoE Endoscopic Reference Score, patient global assessment and symptom-based EoE activity index from baseline to end of treatment (Week 8).

CONCLUSIONS:

APT-1011 was safe and well tolerated in adolescents and adults with EoE. Exploratory efficacy outcomes demonstrated improvement in histologic and endoscopic findings as well evidence of symptom improvement. The results of this study support the continued development of APT-1011 for the treatment of EoE (NCT-01386112).

• Authors: Ikuo Hirano, Ekaterina Safroneeva, Marie C Roumet, Gail M Comer, Gina Eagle, Alain Schoepfer, Gary W Falk
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 51 Issue 8 Pg. 750-759 (04 2020) ISSN: 1365-2036 [Electronic] England
• PMID: 32149424 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 John Wiley & Sons Ltd.

Chemical References

• APT-1011
• Placebos
• Tablets
• Fluticasone

Topics

• Administration, Oral
• Adolescent
• Adult
• Child
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Compounding
• Eosinophilic Esophagitis (drug therapy)
• Female
• Fluticasone (administration & dosage, adverse effects)
• Humans
• Male
• Middle Aged
• Placebos
• Severity of Illness Index
• Tablets
• Treatment Outcome
• United States
• Young Adult