Two phase ii randomized trials on the CRTh2 antagonist AZD1981 in adults with asthma
(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 In study 1, patients with stable asthma (forced expiratory volume in 1 second [FEV1]: 65%−110%) were withdrawn from ICS (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 In study 1, patients with stable asthma (forced expiratory volume in 1 second [FEV1]: 65%−110%) were withdrawn from ICS (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.
(Less)
- author
- Kuna, Piotr ; Bjermer, Leif LU and Tornling, Göran
- organization
- publishing date
- 2016-08-31
- 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
- pmid:27621597
- 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
- 2024-06-14 18:56:28
@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 (<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}},
keywords = {{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}},
doi = {{10.2147/DDDT.S105142}},
volume = {{10}},
year = {{2016}},
}