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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Summary for Change From Baseline of Mean Global Semi-quantitative Score Values for Neutrophils in Bronchial Biopsies
研究概览
简要总结
Distribution of neutrophils in bronchial mucosal tissue in asthma patients before and after 4 wk treatment with AZD 5069
详细描述
The purpose is to investigate the bronchial tissue neutrophil counts and distribution in asthma patients after 4 week oral treatment with AZD 5069
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients of Caucasian origin, aged between 18 to 65 years, inclusive, at the time informed consent is obtained.
- •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
- •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
- •Increased number of neutrophils in induced sputum samples at baseline, with a relative neutrophil count of ≥ 50% of total sputum cell count
- •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.
排除标准
- •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
- •History of severe asthma exacerbation requiring hospitalization within the last 12 months before screening.
- •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.
- •Moderate to severe airflow limitation (FEV1 <70% PN)
- •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.
研究组 & 干预措施
1
oral BD administration of 45 mg AZD5069
干预措施: AZD5069 (Drug)
结局指标
主要结局
Summary for Change From Baseline of Mean Global Semi-quantitative Score Values for Neutrophils in Bronchial Biopsies
时间窗: Baseline and Week 4
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.
Summary for Change From Baseline Neutrophils in Sputum
时间窗: Baseline, Day 8, Day 22 and Day29
Change from Baseline reflects the Day 8, Day22 and Day29 minus the baseline value.
Summary for Change From Baseline Neutrophil Cell Counts in Blood
时间窗: Baseline, Day 2, Day 8, Day 15, Day 22, Day29 and Day 34
Change from Baseline reflects the Day 2, Day 8, Day 15, Day 22, Day29 and Day 34 minus the baseline value
次要结局
- Summary for Change From Baseline for MMP-9 by Type of Sample(Baseline and Day 29)
- Summary for Change From Baseline for IL-8 by Type of Sample(Baseline and Day 29)
- Summary for Change From Baseline for GRO-alpha by Type of Sample(Baseline and Day 29)
- Summary Statistics for AUC0-4hrs on Day 29/ Visit T7 (PK Analysis Set)(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)(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)(At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7))
- Number of Adverse Events(Up to 40 days)
- Number of Participants With Adverse Events(Up to 40 days)
- Summary Statistics for Patient Diary Variables (Day Time)(Up to 44 days)
- Summary Statistics for Patient Diary Variables (Night Time)(Up to 44 days)