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Distribution of neutrophils in bronchial mucosal tissue in asthma patients before and after 4 wk treatment with AZD 5069
The purpose is to investigate the bronchial tissue neutrophil counts and distribution in asthma patients after 4 week oral treatment with AZD 5069
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | oral BD administration of 45 mg AZD5069 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD5069 | Drug | oral BD administration of 45 mg AZD5069 |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Kai Richter, MSD | Astrazeneca Sweden | Study Director |
| Klaus F Rabe, MD | Lung Clinic Grosshansdorf Germany | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Großhansdorf | Germany |
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Thirteen patients were screened; 8 patients were screening failures, 5 patients were enrolled in the study and received treatment with AZD5069.
First patient enrolled: 11 March 2014. Last patient completed: 18 August 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | AZD5069 | AZD5069 45mg oral twice daily (BID) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | AZD5069 | AZD5069 45mg oral twice daily (BID) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | PD analysis set | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Week 4 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AZD5069 | AZD5069 45mg oral twice daily (BID) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Larsson, Bengt | AstraZeneca | +46 (0) 317064277 | ClinicalTrialTransparency@astrazeneca.com |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C000597960 | N-(2-(2,3-difluoro-6-benzylthio)-6-(3,4-dihydroxybutan-2-yloxy)pyrimidin-4-yl)azetidine-1-sulfonamide |
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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 |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
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| Primary | Summary for Change From Baseline Neutrophils in Sputum | Change from Baseline reflects the Day 8, Day22 and Day29 minus the baseline value. | PD analysis set | Posted | Mean | Standard Deviation | 10^9 cells/L | Baseline, Day 8, Day 22 and Day29 |
|
|
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| Primary | 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 | PD Analysis | Posted | Mean | Standard Deviation | 10^9 cells/L | Baseline, Day 2, Day 8, Day 15, Day 22, Day29 and Day 34 |
|
|
|
| Secondary | Summary for Change From Baseline for IL-8 by Type of Sample | Change from baseline reflects the Day 29 value minus the baseline value. | PD analysis set | Posted | Mean | Standard Deviation | pg/ml | Baseline and Day 29 |
|
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|
| Secondary | Summary for Change From Baseline for GRO-alpha by Type of Sample | Change from baseline reflects the Day 29 value minus the baseline value. | PD analysis set | Posted | Mean | Standard Deviation | pg/ml | Baseline and Day 29 |
|
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| Secondary | Summary for Change From Baseline for MMP-9 by Type of Sample | Change from baseline reflects the Day 29 value minus the baseline value. | PD analysis | Posted | Mean | Standard Deviation | ng/ml | Baseline and Day 29 |
|
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| Secondary | 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. | Posted | Geometric Mean | Standard Error | h*nmol/L | At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7) |
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| Secondary | 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. | Posted | Geometric Mean | Standard Error | nmol/L | At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7) |
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| Secondary | 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. | Posted | Geometric Mean | Standard Error | nmol/L | At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7) |
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| Secondary | Number of Adverse Events | Summary of number of adverse events (safety set) | Posted | Number | adverse events | Up to 40 days |
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| Secondary | Number of Participants With Adverse Events | Summary of number of participants with adverse events (safety set) | Posted | Number | Participants | Up to 40 days |
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|
| Secondary | 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. | Posted | Number | Observations | Up to 44 days | Observation | Participants |
|
|
|
| Secondary | 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. | Posted | Number | Observations | Up to 44 days | observations | Participants |
|
|
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| 0 |
| 5 |
| 4 |
| 5 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Obstructive airways | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Neutropil count decreased | Investigations | MedDRA 17.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 17.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| Day 22 |
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| Day 29 |
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| Day 34 |
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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