The Study Will Evaluate the Efficacy of AZD5423 in Patients With Mild Asthma Challenged With an Inhaled Allergen (Allergen)

A Double-blind, Double-dummy, Randomised, Placebo-controlled, 4-way, Crossover, Multi-centre Phase II Study With Budesonide as an Active Control to Evaluate the Efficacy and Safety of 2 Doses of Inhaled AZD5423 Over 7 Days in Patients With Mild Allergic Asthma Challenged With an Inhaled Allergen

The purpose of this study is to evaluate the efficacy of AZD5423 in patients with mild asthma challenged with an inhaled allergen.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: AZD5423; Drug: Placebo; Drug: Budesonide 200 microgram

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada
    • Research Site
  • Alberta
    • Calgary, Alberta, Canada
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada
      • Research Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-60 years of age
• Pre-bronchodilatory FEV1 ≥70% of predicted normal allergic asthmatic with a history of episodic wheeze
• Positive allergen induced early and late airway bronchoconstriction showing ≥ 20% fall in FEV1 for the early and ≥ 15% for the late response
• Positive skin prick test to common aeroallergens

Exclusion Criteria:

• Any clinically significant disease or disorder
• Any clinically relevant abnormal finding at screening examinations
• Smoker or ex-smoker who has stopped smoking < 12 months prior to study start
• Worsening of asthma or respiratory infection within 6 weeks from visit 1
• Allergen-specific immunotherapy within 6 months prior to visit 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 4; Placebo	Drug: Placebo; Solution for nebulisation once daily 7 days
Experimental: 1; AZD5423 75ug	Drug: AZD5423; Suspension for nebulisation once daily 7 days; Drug: Placebo; Solution for nebulisation once daily 7 days
Experimental: 2; AZD5423 300ug	Drug: AZD5423; Suspension for nebulisation once daily 7 days; Drug: Placebo; Solution for nebulisation once daily 7 days
Active Comparator: 3; Budesonide 200 microgram	Drug: Placebo; Solution for nebulisation once daily 7 days; Drug: Budesonide 200 microgram; Dry powder for inhalation twice daily 7 days; Other Names: Pulmicort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late Allergic Response (LAR) by Assessment of Minimum Percentage of FEV1 3-7 Hours Post Allergen Challenge Compared to Pre Allergen Challenge FEV1	LAR was assessed on Day 6 as minimum percentage of FEV1 over 3 to 7 hours based on the analysis of the minimum percentage of FEV1 remaining over 3 to 7 hours post allergen challenge (post AC) compared to pre allergen challenge (pre AC) FEV1	From Randomization to end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Allergic Response (EAR) by Assessment of Minimum Percentage of FEV1 0-3 h Post Allergen Challenge	Minimum Percentage of FEV1 over 0 to 3 hours post allergen challenge compared to pre allergen challenge FEV1	From Randomization to end of treatment
Area Under the Curve (AUC) for FEV1 Over 0-3 and 3-7 h Post Allergen Challenge	AUC was assessed as average percentage of FEV1 remaining 0 to 3 hours and 3 to 7 hours post allergen challenge compared to pre allergen challenge FEV1	From Randomization to end of treatment
Airway Hyperresponsiveness by Assessment of Methacholine PC20	The methacholine challenge was performed on Day 1 (pre dose), Day 5 ([post dose] pre AC), and Day 7 ([post dose] 24 hours post AC)	Day 1 (pre-dose)
Airway Hyperresponsiveness by Assessment of Methacholine PC20	The methacholine challenge was performed on Day 1 (pre dose), Day 5 ([post dose] pre AC), and Day 7 ([post dose] 24 hours post AC)	Day 5 ([post-dose] pre allergen challenge)
Airway Hyperresponsiveness by Assessment of Methacholine PC20	The methacholine challenge was performed on Day 1 (pre dose), Day 5 ([post dose] pre AC), and Day 7 ([post dose] 24 hours post AC)	Day 7 ([post-dose] 24 hours post allergen challenge)
Changes in Sputum Eosinophils Differentials (Percentage)	The change form baseline in percentage of sputum eosinophils was assessed on Day 5 (post dose) ,Day 6 ([post dose] 7 hours post allergen challenge) and Day 7 ([post dose] 24 hours post allergen challenge)	Day 5 (post dose)
Changes in Sputum Eosinophils Differentials (Percentage)	The change form baseline in percentage of sputum eosinophils was assessed on Day 5 (post dose) ,Day 6 ([post dose] 7 hours post allergen challenge) and Day 7 ([post dose] 24 hours post allergen challenge)	Day 6 ([post dose] 7 hours post allergen challenge)
Changes in Sputum Eosinophils Differentials (Percentage)	The change form baseline in percentage of sputum eosinophils was assessed on Day 5 (post dose) ,Day 6 ([post dose] 7 hours post allergen challenge) and Day 7 ([post dose] 24 hours post allergen challenge)	Day 7 ([post dose] 24 hours post allergen challenge)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Christer Hultquist, AstraZeneca R&D, Mölndal, Sweden

Publications and helpful links

General Publications

• Gauvreau GM, Boulet LP, Leigh R, Cockcroft DW, Killian KJ, Davis BE, Deschesnes F, Watson RM, Swystun V, Mardh CK, Wessman P, Jorup C, Aurivillius M, O'Byrne PM. A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses. Am J Respir Crit Care Med. 2015 Jan 15;191(2):161-7. doi: 10.1164/rccm.201404-0623OC.

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: October 15, 2010
• First Submitted That Met QC Criteria: October 20, 2010
• First Posted (Estimate): October 21, 2010

Study Record Updates

• Last Update Posted (Estimate): April 2, 2015
• Last Update Submitted That Met QC Criteria: March 31, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Asthma; Allergen Challenge; Inhaled selective glucocorticoid receptor agonist (iSEGRA)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: D2340C00005