Distribution of Neutrophils in Bronchial Mucosal Tissue in Asthma Patients Before and After 4 Weeks Treatment With AZD 5069

An Explorative Investigation to Study the Relationship and Distribution of Neutrophils in Bronchial Mucosal Tissue, Induced Sputum and Blood After Administration of 45 mg BD AZD 5069 for 4 Weeks to Patients With Moderate Persistent Neutrophilic Asthma

Distribution of neutrophils in bronchial mucosal tissue in asthma patients before and after 4 wk treatment with AZD 5069

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: AZD5069

Detailed Description

The purpose is to investigate the bronchial tissue neutrophil counts and distribution in asthma patients after 4 week oral treatment with AZD 5069

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Grosshansdorf, Germany
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients of Caucasian origin, aged between 18 to 65 years, inclusive, at the time informed consent is obtained.
2. Physician based (according to GINA 2011) diagnosis of asthma for at least 6 months prior to the date informed consent is obtained and confirmed by 1 of the detailed respiratory criteria stated in the CSP
3. Morning prebronchodilator (ie, after abstinence from short-acting and long-acting ß-agonist treatment for ≥ 6 and ≥ 12 hours, respectively) FEV1 of ≥70% of predicted normal (PN) for age, sex and height at enrolment
4. Increased number of neutrophils in induced sputum samples at baseline, with a relative neutrophil count of ≥ 50% of total sputum cell count
5. Physician prescribed daily use of medium or high dose ICS (≥ fluticasone 250 μg to ≤ 1.000 µg or the equivalent daily, as defined in GINA 2011; see CSP Appendix E) plus LABA.

Exclusion Criteria:

1. History of clinically relevant allergies or idiosyncrasies to AZD5069 or other investigational CXCR2 antagonists, or any inactive ingredient(s) of the IMP, or tool-substances (eg, salbutamol, local anaesthetics) used for the purpose of this study
2. History of severe asthma exacerbation requiring hospitalization within the last 12 months before screening.
3. Asthma exacerbation requiring a treatment course of systemic (ie, oral or parenteral) corticosteroids within the 3 months before screening or ≥ 3 courses within the last 12 months before screening.
4. Moderate to severe airflow limitation (FEV1 <70% PN)

5. Any chronic lower respiratory disease other than asthma (see CSP for details) that, as judged by the Investigator or Medical Monitor, would interfere with the evaluation of the IMP or interpretation of patient safety or study results.

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Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; oral BD administration of 45 mg AZD5069	Drug: AZD5069; oral BD administration of 45 mg AZD5069

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary for Change From Baseline of Mean Global Semi-quantitative Score Values for Neutrophils in Bronchial Biopsies	Change from baseline reflects the Week 4 value minus the baseline value. Baseline value is Day-14 measurement. For semi-quantitative scores, 1= few number of Neutrophils, 2= moderate number of Neutrophils, 3= abundant of Neutrophils. For this end point the reduction in mean of semi-quantitative (arbitrary) scores indicates better result, i.e. lower numbers of Neutrophils. The scores given for the biopsies taken at screening and end of treatment is the mean global semi-quantitative scores for the three compartments intraepithelial, subepithelial and submucosal.	Baseline and Week 4
Summary for Change From Baseline Neutrophils in Sputum	Change from Baseline reflects the Day 8, Day22 and Day29 minus the baseline value.	Baseline, Day 8, Day 22 and Day29
Summary for Change From Baseline Neutrophil Cell Counts in Blood	Change from Baseline reflects the Day 2, Day 8, Day 15, Day 22, Day29 and Day 34 minus the baseline value	Baseline, Day 2, Day 8, Day 15, Day 22, Day29 and Day 34

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary for Change From Baseline for IL-8 by Type of Sample	Change from baseline reflects the Day 29 value minus the baseline value.	Baseline and Day 29
Summary for Change From Baseline for GRO-alpha by Type of Sample	Change from baseline reflects the Day 29 value minus the baseline value.	Baseline and Day 29
Summary for Change From Baseline for MMP-9 by Type of Sample	Change from baseline reflects the Day 29 value minus the baseline value.	Baseline and Day 29
Summary Statistics for AUC0-4hrs on Day 29/ Visit T7 (PK Analysis Set)	Summary statistics including geometric mean and standard error for AUC0-4hrs on Day 29/ Visit T7 (PK analysis set). Plasma concentration data beyond 0.5 hrs post dose at Day 29 were missing for one patient. For this patient only Cmin value was reported and the AUC0-4hrs and Cmax values were not reported.	At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7)
Summary Statistics for Cmin on Day 29/ Visit T7 (PK Analysis Set)	Summary statistics including geometric mean and standard error for Cmin on Day 29/ Visit T7 (PK analysis set). Plasma concentration data beyond 0.5 hrs post dose at Day 29 were missing for one patient. For this patient only Cmin value was reported and the AUC0-4hrs and Cmax values were not reported.	At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7)
Summary Statistics for Cmax on Day 29/ Visit T7 (PK Analysis Set)	Summary statistics including geometric mean and standard error for Cmax on Day 29/ Visit T7 (PK analysis set). Plasma concentration data beyond 0.5 hrs post dose at Day 29 were missing for one patient. For this patient only Cmin value was reported and the AUC0-4hrs and Cmax values were not reported.	At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7)
Number of Adverse Events	Summary of number of adverse events (safety set)	Up to 40 days
Number of Participants With Adverse Events	Summary of number of participants with adverse events (safety set)	Up to 40 days
Summary Statistics for Patient Diary Variables (Day Time)	Summary statistics for patient diary variable, observations with no asthma symptoms (day time), by period (safety set). The screening period was Day -14 to -1. Period 1 was the first half of treatment period, Day 1 to daytime record Day 15. Period 2 was the second half of treatment period, night-time record Day 15 to night-time record Day 29+1. One participant left the study on day 2, due to adverse event.	Up to 44 days
Summary Statistics for Patient Diary Variables (Night Time)	Summary statistics for patient diary variable, observations with no asthma symptoms (night time), by period (safety set). The screening period was Day -14 to -1. Period 1 was the first half of treatment period, Day 1 to daytime record Day 15. Period 2 was the second half of treatment period, night-time record Day 15 to night-time record Day 29+1. One participant left the study on day 2, due to adverse event.	Up to 44 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Kai Richter, MSD, AstraZeneca Sweden; Principal Investigator: Klaus F Rabe, MD, Lung Clinic Grosshansdorf Germany

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: June 17, 2013
• First Submitted That Met QC Criteria: June 27, 2013
• First Posted (Estimate): July 1, 2013

Study Record Updates

• Last Update Posted (Estimate): February 25, 2016
• Last Update Submitted That Met QC Criteria: January 28, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: D3551C00003