Clinical trial NCT01890148: Distribution of Neutrophils in Bronchial Mucosal Tissue in Asthma Patients Before and After 4 Weeks Treatment With AZD 5069
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-07-01
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

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

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

Eligibility criteria: 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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Primary outcomes:
measure: Summary for Change From Baseline of Mean Global Semi-quantitative Score Values for Neutrophils in Bronchial Biopsies
timeFrame: Baseline and Week 4
measure: Summary for Change From Baseline Neutrophils in Sputum
timeFrame: Baseline, Day 8, Day 22 and Day29
measure: Summary for Change From Baseline Neutrophil Cell Counts in Blood
timeFrame: Baseline, Day 2, Day 8, Day 15, Day 22, Day29 and Day 34
Secondary outcomes:
measure: Summary for Change From Baseline for IL-8 by Type of Sample
timeFrame: Baseline and Day 29
measure: Summary for Change From Baseline for GRO-alpha by Type of Sample
timeFrame: Baseline and Day 29
measure: Summary for Change From Baseline for MMP-9 by Type of Sample
timeFrame: Baseline and Day 29
measure: Summary Statistics for AUC0-4hrs on Day 29/ Visit T7 (PK Analysis Set)
timeFrame: At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7)
measure: Summary Statistics for Cmin on Day 29/ Visit T7 (PK Analysis Set)
timeFrame: At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7)
measure: Summary Statistics for Cmax on Day 29/ Visit T7 (PK Analysis Set)
timeFrame: At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7)
measure: Number of Adverse Events
timeFrame: Up to 40 days
measure: Number of Participants With Adverse Events
timeFrame: Up to 40 days
measure: Summary Statistics for Patient Diary Variables (Day Time)
timeFrame: Up to 44 days
measure: Summary Statistics for Patient Diary Variables (Night Time)
timeFrame: Up to 44 days
Other outcomes:
Locations:
city: Grosshansdorf
country: Germany
facility: Research Site
Study officials:
affiliation: Astrazeneca Sweden
name: Kai Richter, MSD
role: STUDY_DIRECTOR
affiliation: Lung Clinic Grosshansdorf Germany
name: Klaus F Rabe, MD
role: PRINCIPAL_INVESTIGATOR
References: