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

Ikuo Hirano; Ekaterina Safroneeva; Marie C. Roumet; Gail M. Comer; Gina Eagle; Alain Schoepfer; Gary W. Falk

doi:10.1111/apt.15670

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

Ikuo Hirano^*, Ekaterina Safroneeva, Marie C. Roumet, Gail M. Comer, Gina Eagle, Alain Schoepfer, Gary W. Falk

^*Corresponding author for this work

Medicine, Gastroenterology Division

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

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).

Original language	English (US)
Pages (from-to)	750-759
Number of pages	10
Journal	Alimentary Pharmacology and Therapeutics
Volume	51
Issue number	8
DOIs	https://doi.org/10.1111/apt.15670
State	Published - Apr 1 2020

Funding

This study was funded by Adare Pharmaceuticals, Inc. The study sponsor had a role in the study design, collection, analysis and interpretation of the data, as well as in the writing of the report. Medical writing and editorial support were provided by Hospicom (Cold Spring, NY, USA) and was funded by Adare Pharmaceuticals, Inc. (Lawrenceville, NJ, USA). Declaration of personal interests: IH has received research funding from Adare, Allakos, Meritage, Celgene/Receptos, Regeneron, Shire/Takeda; and consulting fees from Adare, Allakos, Arena, AstraZeneca, Biorasi, Celgene/Receptos, Eli Lilly, EsoCap, Gossamer Bio, Regeneron, Shire/Takeda. GMC is a consultant for Adare. ES has served as a consultant for Adare, Aptalis, Novartis, Receptos and Regeneron. MCR has no conflicts of interest to report. AS has served as consultant for AbbVie, Adare, Falk Pharma GmbH, MSD, Receptos, Regeneron, Novartis, Pfizer, Takeda and Vifor, and has received research funding from Adare, Falk Pharma GmbH, Receptos and Regeneron. GWF has received research support from Allakos, Receptos/Celgene and Regeneron, and has received research support and has served as a consultant for Adare and Shire/Takeda. GE has served as a consultant for and is currently employed by Adare. Medical writing and editorial support were provided by Hospicom (Cold Spring, NY, USA) and was funded by Adare Pharmaceuticals, Inc. (Lawrenceville, NJ, USA). Declaration of personal interests : IH has received research funding from Adare, Allakos, Meritage, Celgene/Receptos, Regeneron, Shire/Takeda; and consulting fees from Adare, Allakos, Arena, AstraZeneca, Biorasi, Celgene/Receptos, Eli Lilly, EsoCap, Gossamer Bio, Regeneron, Shire/Takeda. GMC is a consultant for Adare. ES has served as a consultant for Adare, Aptalis, Novartis, Receptos and Regeneron. MCR has no conflicts of interest to report. AS has served as consultant for AbbVie, Adare, Falk Pharma GmbH, MSD, Receptos, Regeneron, Novartis, Pfizer, Takeda and Vifor, and has received research funding from Adare, Falk Pharma GmbH, Receptos and Regeneron. GWF has received research support from Allakos, Receptos/Celgene and Regeneron, and has received research support and has served as a consultant for Adare and Shire/Takeda. GE has served as a consultant for and is currently employed by Adare.

ASJC Scopus subject areas

Hepatology
Gastroenterology
Pharmacology (medical)

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title = "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).",

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Randomised clinical trial: the safety and tolerability of fluticasone propionate orally disintegrating tablets versus placebo for eosinophilic oesophagitis. / Hirano, Ikuo; Safroneeva, Ekaterina; Roumet, Marie C. et al.
In: Alimentary Pharmacology and Therapeutics, Vol. 51, No. 8, 01.04.2020, p. 750-759.

Research output: Contribution to journal › Article › peer-review

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T2 - the safety and tolerability of fluticasone propionate orally disintegrating tablets versus placebo for eosinophilic oesophagitis

AU - Hirano, Ikuo

AU - Safroneeva, Ekaterina

AU - Roumet, Marie C.

AU - Comer, Gail M.

AU - Eagle, Gina

AU - Schoepfer, Alain

AU - Falk, Gary W.

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N2 - 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).

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

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