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Two phase ii randomized trials on the CRTh2 antagonist AZD1981 in adults with asthma

Kuna, Piotr; Bjermer, Leif LU and Tornling, Göran (2016) In Drug Design, Development and Therapy 10. p.2759-2770
Abstract

Background: Chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cell (CRTh2) receptor antagonists is being investigated for asthma. Objectives: 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. Patients and 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 In study 1, patients with stable asthma (forced expiratory volume in 1 second [FEV1]: 65%−110%) were withdrawn from ICS (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... (More)

Background: Chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cell (CRTh2) receptor antagonists is being investigated for asthma. Objectives: 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. Patients and 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 In study 1, patients with stable asthma (forced expiratory volume in 1 second [FEV1]: 65%−110%) were withdrawn from ICS (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. Conclusion: Further research may be warranted in atopic patients to fully evaluate the clinical efficacy of AZD1981.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
CRTh2 receptor, Efficacy, Phase II, Prostaglandin D, Respiratory, Th2 cells
in
Drug Design, Development and Therapy
volume
10
pages
12 pages
publisher
Dove Medical Press Ltd.
external identifiers
  • scopus:84985916151
  • wos:000382213500001
ISSN
1177-8881
DOI
10.2147/DDDT.S105142
language
English
LU publication?
yes
id
e2b35016-ba9c-47e8-b427-8f3e3c05899e
date added to LUP
2016-11-30 09:37:12
date last changed
2017-08-06 05:14:15
@article{e2b35016-ba9c-47e8-b427-8f3e3c05899e,
  abstract     = {<p>Background: Chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cell (CRTh2) receptor antagonists is being investigated for asthma. Objectives: 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. Patients and 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 [FEV<sub>1</sub>]: 65%−110%) were withdrawn from ICS (&lt;400 μg/d) and randomized to AZD1981 1,000 mg twice daily (bid) or placebo. In study 2, patients with uncontrolled asthma (FEV<sub>1</sub>: 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, FEV<sub>1</sub> 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 FEV<sub>1</sub> were observed in the majority of atopic patients treated with AZD1981. AZD1981 was well tolerated across treatment groups. Conclusion: Further research may be warranted in atopic patients to fully evaluate the clinical efficacy of AZD1981.</p>},
  author       = {Kuna, Piotr and Bjermer, Leif and Tornling, Göran},
  issn         = {1177-8881},
  keyword      = {CRTh2 receptor,Efficacy,Phase II,Prostaglandin D,Respiratory,Th2 cells},
  language     = {eng},
  month        = {08},
  pages        = {2759--2770},
  publisher    = {Dove Medical Press Ltd.},
  series       = {Drug Design, Development and Therapy},
  title        = {Two phase ii randomized trials on the CRTh2 antagonist AZD1981 in adults with asthma},
  url          = {http://dx.doi.org/10.2147/DDDT.S105142},
  volume       = {10},
  year         = {2016},
}