The Tolerability and Effects of AZD8848 in Allergic Asthma Subjects Challenged With Inhaled Allergen

Phase 2

Completed

• Conditions: Allergic Asthma
• Interventions: Drug: AZD8848; Drug: Placebo

• Registration Number: NCT00999466
• Lead Sponsor: AstraZeneca

Brief Summary

AZD8848 is a new drug that is being tested for the treatment of asthma and allergic rhinitis (hayfever). This study will be in two parts and will include 59 asthmatic patients in total. The first part will investigate the tolerability and safety of AZD8848 while the second part will investigate both the therapeutic effect of AZD8848 and how well patients tolerate the drug.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-10
• Study First Submitted: 2009-10-20
• Study First Submitted QC: 2009-10-20
• Study First Posted: 2009-10-21
• Primary Completion: 2011-02
• Study Completion: 2011-12
• Results First Submitted: 2015-08-31
• Results First Submitted QC: 2015-12-17
• Status Verified: 2016-01
• Results First Posted: 2016-01-26
• Last Update Submitted: 2016-01-28
• Last Update Posted: 2016-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• FEV1 > 70 % of predicted normal pre-bronchodilator
• Documented history of asthma
• Presence of allergic sensitivity

Exclusion Criteria

• Clinically relevant disease and/or abnormality (past or present), which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results of the study, or the patient's ability to participate in the study.
• Symptomatic allergic rhinitis
• Any clinical relevant abnormal findings in physical examination or assessment which may put the patient at risk because of participation in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	AZD8848	AZD8848 (30 μg PILOT part and 60 μg MAIN part)
2	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
FEV1, Late Asthmatic Response (LAR) - 1 Week After Last Dose	1 week after last dose	FEV1, Late Asthmatic Response (LAR), is derived as the ratio of FEV1 AUC 4-10h (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement.
FEV1, Late Asthmatic Response (LAR) - 4 Weeks After Last Dose	4 weeks after last dose	FEV1, Late Asthmatic Response (LAR), is derived as the ratio of FEV1 AUC 4-10h (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement.
FEV1, Late Asthmatic Response (LAR) - Pre-treatment	Pre-treatment (Baseline measurement)	Forced Expiratory Volume in 1 second (FEV1), Late Asthmatic Response (LAR), is derived as the ratio of FEV1 Area Under Curve 4-10 hour post allergen challenge (AUC 4-10h) (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement.

Secondary Outcome Measures

Name	Time	Method
Sputum Cellularity and Cytokines, TNFα - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, IL-8 - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
PC20 Methacholine Challenge - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge	PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1
PC20 Methacholine Challenge - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge	PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1
PC20 Methacholine Challenge - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge	PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1
Sputum Cellularity and Cytokines, TNFα - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
FEV1, Early Asthmatic Response (EAR) - Pre-treatment	Pre-treatment (Baseline measurement)	FEV1, Early Asthmatic Response (EAR), is derived as the ratio of FEV1 Area Under Curve 0-2 hour post allergen challenge (AUC 0-2h) (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement.
PC20 Methacholine Challenge - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge	PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1
Sputum Cellularity and Cytokines, TNFα - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Eosinophils - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, Neutrophils - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, Neutrophils - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, TNFα - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, IL-1β - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, IL-1β - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, IL-5 - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, IL-6 - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, IL-6 - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, IL-6 - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
FEV1, Early Asthmatic Response (EAR) - 1 Week After Last Dose	1 week after last dose	FEV1, Early Asthmatic Response (EAR), is derived as the ratio of FEV1 AUC 0-2h (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement.
FEV1, Early Asthmatic Response (EAR) - 4 Weeks After Last Dose	4 weeks after last dose	FEV1, Early Asthmatic Response (EAR), is derived as the ratio of FEV1 AUC 0-2h (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement.
Sputum Cellularity and Cytokines, IL-5 - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, IL-5 - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, IL-6 - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, IL-10 - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, IL-10 - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, IL-10 - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, IL-13 - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
PC20 Methacholine Challenge - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge	PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1
PC20 Methacholine Challenge - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge	PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1
Sputum Cellularity and Cytokines, Tumour Necrosis Factor Alpha (TNFα) - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, TNFα - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Interleukin-1β (IL-1β) - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, IL-1β - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, IL-1β - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, IL-1β - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Interleukin-5 (IL-5) - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, IL-5 - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, IL-5 - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, IL-6 - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Interleukin-8 (IL-8) - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, IL-8 - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Interleukin-6 (IL-6) - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, IL-8 - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, IL-8 - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, IL-10 - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, Interleukin-13 (IL-13) - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, IL-13 - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Eosinophils - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Macrophages - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, Epithelial Cells - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, IL-8 - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Total Cells/g - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, Total Cells/g - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, Total Cells/g - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Total Cells/g - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Total Cells/g - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Eosinophils - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Neutrophils - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Macrophages - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, Macrophages - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Macrophages - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Macrophages - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Lymphocytes - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, Epithelial Cells - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, Epithelial Cells - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Epithelial Cells - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Interleukin-10 (IL-10) - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, IL-10 - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, IL-13 - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Total Cells/g - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Eosinophils - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, Eosinophils - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Eosinophils - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Neutrophils - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Neutrophils - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Macrophages - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Lymphocytes - Pre-treatment, Post Allergen Challenge	Pre-treatment, post allergen challenge
Sputum Cellularity and Cytokines, Lymphocytes - 4 Weeks After Last Dose, Pre Allergen Challenge	4 weeks after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Epithelial Cells - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, IL-13 - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, IL-13 - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Neutrophils - Pre-treatment, Pre Allergen Challenge	Pre-treatment, pre allergen challenge
Sputum Cellularity and Cytokines, Lymphocytes - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge
Sputum Cellularity and Cytokines, Lymphocytes - 1 Week After Last Dose, Post Allergen Challenge	1 week after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Lymphocytes - 4 Weeks After Last Dose, Post Allergen Challenge	4 weeks after last dose, post allergen challenge
Sputum Cellularity and Cytokines, Epithelial Cells - 1 Week After Last Dose, Pre Allergen Challenge	1 week after last dose, pre allergen challenge

Trial Locations

Locations (1)

Research Site; 🇬🇧 Manchester, United Kingdom