A phase 2a study of toreforant, a histamine H4 receptor antagonist, in eosinophilic asthma.

Abstract

BACKGROUND:

Data from preclinical and clinical studies support the evaluation of histamine 4 receptor antagonists in the treatment of asthma. Toreforant is a selective histamine 4 receptor antagonist that could be effective in patients with eosinophilic asthma.

OBJECTIVE:

To evaluate the efficacy and safety of toreforant in patients with eosinophilic, persistent asthma that was inadequately controlled despite current treatment.

METHODS:

In this phase 2a, multicenter, randomized, double-blinded, parallel-group, placebo-controlled, proof-of-concept study, 162 eligible patients were randomized (1:1) to placebo or 30 mg of toreforant once daily through week 24 and followed for 4 weeks. The primary end point was change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at week 16. Secondary end points included change from baseline at week 16 in postbronchodilator percent-predicted forced expiratory volume in 1 second, Asthma Control Questionnaire scores, weekly averages of Daytime and Nighttime Asthma Diary Symptom Scores, and weekly average of number of puffs in a day that rescue medication was used.

RESULTS:

There was no significant difference between groups in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at week 16 (difference in least-square means -0.19%; 95% confidence interval -3.01 to 2.64; P = .90). Similarly, there were no significant differences between groups at week 16 in changes from baseline in the secondary end points (P ≥ .30). Toreforant was generally well tolerated. No deaths or serious adverse events were reported at any time point.

CONCLUSION:

Toreforant, at the dose tested, failed to provide therapeutic benefit in this population of patients with uncontrolled, eosinophilic, persistent asthma.

TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01823016.

• Authors: Alexa P Kollmeier, Elliot S Barnathan, Christopher O'Brien, Bin Chen, Yichuan Karen Xia, Bei Zhou, Matthew J Loza, Philip E Silkoff, Michelle Ge, Robin L Thurmond
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 121 Issue 5 Pg. 568-574 (11 2018) ISSN: 1534-4436 [Electronic] United States
• PMID: 30102965 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 American College of Allergy, Asthma 8 Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Bronchodilator Agents
• Histamine Antagonists
• Receptors, Histamine H4

Topics

• Asthma (drug therapy)
• Bronchodilator Agents (therapeutic use)
• Double-Blind Method
• Female
• Forced Expiratory Volume
• Histamine Antagonists (adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Proof of Concept Study
• Pulmonary Eosinophilia (drug therapy)
• Receptors, Histamine H4 (antagonists & inhibitors)
• Treatment Outcome
• United States