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Authors Bateman ED, O'Brien C, Rugman P, Luke S, Ivanov S, Uddin M
Received 26 July 2017
Accepted for publication 13 December 2017
Published 4 May 2018 Volume 2018:12 Pages 1093—1106
DOI https://doi.org/10.2147/DDDT.S147389
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 2
Editor who approved publication: Professor Manfred Ogris
Objectives: To evaluate the efficacy and safety of AZD1981, a potent, specific
antagonist of the CRTh2 receptor, as add-on therapy to inhaled corticosteroids
(ICS) and long-acting β2-agonists (LABA), in patients with persistent asthma with an allergic
component.
Patients and
methods: In this placebo-controlled,
parallel-group Phase IIb study, patients with persistent atopic asthma on ICS
and LABA were randomized to receive 12 weeks of treatment with placebo or
AZD1981 (80 mg daily, 200 mg daily, and 10 mg, 40 mg, 100 mg, or 400 mg twice
daily [BID]). The primary end point was the mean change from baseline in
predose, prebronchodilator forced expiratory volume in 1 second (FEV1) averaged over weeks 2, 4, 8, and 12 in the AZD1981-treatment group vs
the placebo group. Secondary end points included other measures of lung
function, symptoms, and asthma control, as well as standard measures of safety.
Results: In total, 1,140 patients (99.7%) received study treatment. There
were improvements in the primary end point across all treatment groups over 12
weeks of treatment. However, the improvement for the highest AZD1981 dose (400
mg BID) vs placebo was not statistically significant (0.02 L, P =0.58), preventing interpretation
of statistical testing for the lower doses. AZD1981 was well tolerated, and the
incidence of adverse events was comparable across placebo and treatment groups.
Conclusion: In patients with allergic asthma receiving ICS and LABA therapy, the
addition of AZD1981 at doses up to 400 mg BID failed to produce a clinically
relevant improvement in lung function or any other measured end point, but
appeared to have an acceptable safety profile. This clinical study is
registered with ClinicalTrials.gov (NCT01197794).
Keywords: allergic asthma, AZD1981, CRTh2 antagonist, efficacy, safety,
eosinophils