Trial Outcomes & Findings for Distribution of Neutrophils in Bronchial Mucosal Tissue in Asthma Patients Before and After 4 Weeks Treatment With AZD 5069 (NCT NCT01890148)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

13 participants

Primary outcome timeframe

Baseline and Week 4

Results posted on

2016-02-25

Participant Flow

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.

Participant milestones

Participant milestones
Measure	AZD5069 AZD5069 45mg oral twice daily (BID)
Overall Study STARTED	5
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD5069 AZD5069 45mg oral twice daily (BID)
Overall Study Adverse Event	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD5069 n=5 Participants AZD5069 45mg oral twice daily (BID)
Age, Continuous	46.8 Years STANDARD_DEVIATION 10.3 • n=93 Participants
Sex: Female, Male Female	1 Participants n=93 Participants
Sex: Female, Male Male	4 Participants n=93 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: PD analysis set

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.

Outcome measures

Outcome measures
Measure	AZD5069 n=4 Participants AZD5069 45mg oral twice daily (BID)
Summary for Change From Baseline of Mean Global Semi-quantitative Score Values for Neutrophils in Bronchial Biopsies	-1.21 Units on a scale Standard Deviation 0.54

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 22 and Day29

Population: PD analysis set

Change from Baseline reflects the Day 8, Day22 and Day29 minus the baseline value.

Outcome measures

Outcome measures
Measure	AZD5069 n=4 Participants AZD5069 45mg oral twice daily (BID)
Summary for Change From Baseline Neutrophils in Sputum Day 8	-4.294 10^9 cells/L Standard Deviation 3.062
Summary for Change From Baseline Neutrophils in Sputum Day 22	-6.670 10^9 cells/L Standard Deviation 3.751
Summary for Change From Baseline Neutrophils in Sputum Day 29	-3.849 10^9 cells/L Standard Deviation 1.861

PRIMARY outcome

Timeframe: Baseline, Day 2, Day 8, Day 15, Day 22, Day29 and Day 34

Population: PD Analysis

Change from Baseline reflects the Day 2, Day 8, Day 15, Day 22, Day29 and Day 34 minus the baseline value

Outcome measures

Outcome measures
Measure	AZD5069 n=4 Participants AZD5069 45mg oral twice daily (BID)
Summary for Change From Baseline Neutrophil Cell Counts in Blood Day 2	-2.517 10^9 cells/L Standard Deviation 0.420
Summary for Change From Baseline Neutrophil Cell Counts in Blood Day 8	-1.494 10^9 cells/L Standard Deviation 0.559
Summary for Change From Baseline Neutrophil Cell Counts in Blood Day 15	-1.985 10^9 cells/L Standard Deviation 0.425
Summary for Change From Baseline Neutrophil Cell Counts in Blood Day 22	-1.658 10^9 cells/L Standard Deviation 0.237
Summary for Change From Baseline Neutrophil Cell Counts in Blood Day 29	-1.178 10^9 cells/L Standard Deviation 1.375
Summary for Change From Baseline Neutrophil Cell Counts in Blood Day 34	-0.306 10^9 cells/L Standard Deviation 0.200

SECONDARY outcome

Timeframe: Baseline and Day 29

Population: PD analysis set

Change from baseline reflects the Day 29 value minus the baseline value.

Outcome measures

Outcome measures
Measure	AZD5069 n=4 Participants AZD5069 45mg oral twice daily (BID)
Summary for Change From Baseline for IL-8 by Type of Sample IL-8 in Serum	46.88 pg/ml Standard Deviation 34.13
Summary for Change From Baseline for IL-8 by Type of Sample IL-8 in Sputum	5780.75 pg/ml Standard Deviation 3763.83

SECONDARY outcome

Timeframe: Baseline and Day 29

Population: PD analysis set

Change from baseline reflects the Day 29 value minus the baseline value.

Outcome measures

Outcome measures
Measure	AZD5069 n=4 Participants AZD5069 45mg oral twice daily (BID)
Summary for Change From Baseline for GRO-alpha by Type of Sample GRO-alpha in Serum	179.75 pg/ml Standard Deviation 98.20
Summary for Change From Baseline for GRO-alpha by Type of Sample GRO-alpha in Sputum	7352.50 pg/ml Standard Deviation 22373.99

SECONDARY outcome

Timeframe: Baseline and Day 29

Population: PD analysis

Change from baseline reflects the Day 29 value minus the baseline value.

Outcome measures

Outcome measures
Measure	AZD5069 n=4 Participants AZD5069 45mg oral twice daily (BID)
Summary for Change From Baseline for MMP-9 by Type of Sample MMP-9 in Serum	-157.75 ng/ml Standard Deviation 289.76
Summary for Change From Baseline for MMP-9 by Type of Sample MMP-9 in Sputum	-80.75 ng/ml Standard Deviation 178.55

SECONDARY outcome

Timeframe: At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7)

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.

Outcome measures

Outcome measures
Measure	AZD5069 n=3 Participants AZD5069 45mg oral twice daily (BID)
Summary Statistics for AUC0-4hrs on Day 29/ Visit T7 (PK Analysis Set)	8571.72 h*nmol/L Standard Error 2421.99

SECONDARY outcome

Timeframe: At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7)

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.

Outcome measures

Outcome measures
Measure	AZD5069 n=4 Participants AZD5069 45mg oral twice daily (BID)
Summary Statistics for Cmin on Day 29/ Visit T7 (PK Analysis Set)	466.92 nmol/L Standard Error 272.3

SECONDARY outcome

Timeframe: At 0, 0.5, 1, 1.5, 2, 2.5, 3, 4 hours post dose on Day 29 (Visit T7)

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.

Outcome measures

Outcome measures
Measure	AZD5069 n=3 Participants AZD5069 45mg oral twice daily (BID)
Summary Statistics for Cmax on Day 29/ Visit T7 (PK Analysis Set)	3565.76 nmol/L Standard Error 762.84

SECONDARY outcome

Timeframe: Up to 40 days

Summary of number of adverse events (safety set)

Outcome measures

Outcome measures
Measure	AZD5069 n=5 Participants AZD5069 45mg oral twice daily (BID)
Number of Adverse Events Total number of SAEs	0 adverse events
Number of Adverse Events Total number of unique AEs	10 adverse events
Number of Adverse Events Total number of AEs	11 adverse events

SECONDARY outcome

Timeframe: Up to 40 days

Summary of number of participants with adverse events (safety set)

Outcome measures

Outcome measures
Measure	AZD5069 n=5 Participants AZD5069 45mg oral twice daily (BID)
Number of Participants With Adverse Events Total number of subjects with at least one AE	4 Participants
Number of Participants With Adverse Events Number of subjects withdrawn from study due to AE	1 Participants

SECONDARY outcome

Timeframe: Up to 44 days

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.

Outcome measures

Outcome measures
Measure	AZD5069 n=197 Observation AZD5069 45mg oral twice daily (BID)
Summary Statistics for Patient Diary Variables (Day Time) Obs. with No asthma symptoms (Screening; n=55)	6 Observations
Summary Statistics for Patient Diary Variables (Day Time) Obs. with No asthma symptoms (Period1; n=71)	7 Observations
Summary Statistics for Patient Diary Variables (Day Time) Obs. with No asthma symptoms (Period2; n=71)	7 Observations

SECONDARY outcome

Timeframe: Up to 44 days

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.

Outcome measures

Outcome measures
Measure	AZD5069 n=191 observations AZD5069 45mg oral twice daily (BID)
Summary Statistics for Patient Diary Variables (Night Time) Obs. with No asthma symptoms (Screening; n=52)	9 Observations
Summary Statistics for Patient Diary Variables (Night Time) Obs. with No asthma symptoms (Period1; n=69)	2 Observations
Summary Statistics for Patient Diary Variables (Night Time) Obs. with No asthma symptoms (Period2; n=70)	10 Observations

Adverse Events

AZD5069

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	AZD5069 n=5 participants at risk AZD5069 45mg oral twice daily (BID)
Respiratory, thoracic and mediastinal disorders Cough	20.0% 1/5 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnoea	20.0% 1/5 • Number of events 1
Respiratory, thoracic and mediastinal disorders Obstructive airways	20.0% 1/5 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	40.0% 2/5
Gastrointestinal disorders Toothache	20.0% 1/5
Investigations Neutropil count decreased	20.0% 1/5
Nervous system disorders Syncope	20.0% 1/5
Vascular disorders Hypertension	20.0% 1/5
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	20.0% 1/5 • Number of events 1

Additional Information

Larsson, Bengt

AstraZeneca

Phone: +46 (0) 317064277

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60