Two Phase II randomized trials on the CRTh2 antagonist AZD1981 in adults with asthma.
BACKGROUND
Chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cell (CRTh2) receptor antagonists is being investigated for asthma.


OBJECTIVE
The aim of this study was to assess the effects of the CRTh2 receptor antagonist, AZD1981 (with/without inhaled corticosteroids [ICSs]), on lung function and asthma control.


METHODS
Adults aged 18-60 years were enrolled in two randomized, placebo-controlled, parallel-group trials (protocol number: D9830C00003 [study 1, n=209] and protocol number: D9830C00004 [study 2, n=510]). In study 1, patients with stable asthma (forced expiratory volume in 1 second [FEV1]: 65%-110%) were withdrawn from ICS (<400 µg/d) and randomized to AZD1981 1,000 mg twice daily (bid) or placebo. In study 2, patients with uncontrolled asthma (FEV1: 40%-85%) despite ICS therapy (≥500 µg/d) were randomized to 50 mg, 400 mg, or 1,000 mg bid AZD1981 or placebo. The primary efficacy variable for both trials was the change in morning peak expiratory flow after 4 weeks of treatment. Secondary variables included Asthma Control Questionnaire (ACQ-5) scores, FEV1 assessments, safety, and tolerability. In study 2, efficacy was also assessed according to atopic status.


RESULTS
Following 4 weeks of treatment, there was a nonsignificant increase in morning peak expiratory flow on AZD1981 1,000 mg bid (9.5 L/min vs placebo, P=0.086 [study 1] and 12 L/min vs placebo, P=0.16 [study 2]). In study 2, all doses of AZD1981 provided significant improvements in ACQ-5 scores (0.26-0.3 units vs placebo, P=0.010-0.022); however, there was no dose-response relationship. Improved ACQ-5 scores and FEV1 were observed in the majority of atopic patients treated with AZD1981. AZD1981 was well tolerated across treatment groups.


CONCLUSIONS
Further research may be warranted in atopic patients to fully evaluate the clinical efficacy of AZD1981.
Department of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Łódz, Łódz, Poland.
Piotr
P
Kuna
Department of Respiratory Medicine and Allergology, Skane University Hospital, Lund University.
Leif
L
Bjermer
AstraZeneca Research and Development, Molndal; Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institute and Karolinska University Hospital, Solna, Sweden.
Göran
G
Tornling
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D055815:Young Adult
D000085:Acetates; D007211:Indoles; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C569518:AZD1981; C036293:prostaglandin D2 receptor
CRTh2 receptor; Phase II; Th2 cells; efficacy; prostaglandin D2; respiratory