Trial Outcomes & Findings for Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis (NCT NCT01255592)

NCT ID: NCT01255592

Last Updated: 2015-10-08

Results Overview

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 83 participants
• Primary outcome timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
• Results posted on: 2015-10-08

Participant Flow

This multicenter study was conducted in Europe between 27 December 2010 and 13 February 2012.

Participant milestones

Measure	AZD5069 AZD5069 80 mg bd	Placebo Placebo for AZD5069, bd
Overall Study STARTED	26	26
Overall Study COMPLETED	20	25
Overall Study NOT COMPLETED	6	1

Reasons for withdrawal

Measure	AZD5069 AZD5069 80 mg bd	Placebo Placebo for AZD5069, bd
Overall Study Adverse Event	5	0
Overall Study Withdrawal by Subject	1	0
Overall Study Other	0	1

Baseline Characteristics

Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis

Baseline characteristics by cohort

Measure	AZD5069 n=26 Participants AZD5069 80 mg bd	Placebo n=26 Participants Placebo bd	Total n=52 Participants Total of all reporting groups
Age, Continuous	66 years STANDARD_DEVIATION 6.6 • n=5 Participants	65 years STANDARD_DEVIATION 8.8 • n=7 Participants	65 years STANDARD_DEVIATION 7.7 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	12 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	14 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized White	26 participants n=5 Participants	26 participants n=7 Participants	52 participants n=5 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=19 Participants AZD5069 80 mg bd	Placebo n=24 Participants Placebo bd
Ratio of Absolute Neutrophil Cell Count in Sputum at End of Treatment Compared to Baseline	0.31 ratio 90% Confidence Interval 165.925 • Interval 0.2 to 0.5	1.00 ratio 90% Confidence Interval 213.281 • Interval 0.66 to 1.51

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=19 Participants AZD5069 80 mg bd	Placebo n=24 Participants Placebo bd
Ratio of the Percentage Neutrophil Cell Count in Sputum at End of Treatment Compared to Baseline	0.66 ratio 90% Confidence Interval 29.746 • Interval 0.54 to 0.8	1.02 ratio 90% Confidence Interval 56.883 • Interval 0.86 to 1.22

SECONDARY outcome

Timeframe: Baseline and end of treatment (Day 28)

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Patients collected all sputum produced during a 24-hour period at baseline and Day 28.

Outcome measures

Measure	AZD5069 n=20 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Change From Baseline in Weight of 24-hour Sputum Collection	3.51 grams Standard Error 2.455	-3.26 grams Standard Error 2.195

SECONDARY outcome

Timeframe: Baseline to end of treatment (Day 28)

Population: The efficacy analysis set included all patients who were randomized (defined as having a randomization code recorded on the demography case report form), received at least one dose of study medication, and contributed sufficient data for at least one efficacy endpoint.

Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. SVC is the measure of the change in volume of gas in the lungs from complete inspiration to complete expiration.

Outcome measures

Measure	AZD5069 n=23 Participants AZD5069 80 mg bd	Placebo n=26 Participants Placebo bd
Change From Baseline in Slow Vital Capacity (SVC)	0.05 liters Standard Error 0.067	-0.05 liters Standard Error 0.063

SECONDARY outcome

Timeframe: Baseline to end of treatment (Day 28)

Population: The efficacy analysis set included all patients who were randomized (defined as having a randomization code recorded on the demography case report form), received at least one dose of study medication, and contributed sufficient data for at least one efficacy endpoint.

Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FVC is the maximum volume of air which can be exhaled or inspired during a forced maneuver.

Outcome measures

Measure	AZD5069 n=24 Participants AZD5069 80 mg bd	Placebo n=26 Participants Placebo bd
Change From Baseline in Forced Vital Capacity (FVC)	0.07 liters Standard Error 0.056	0.06 liters Standard Error 0.054

SECONDARY outcome

Timeframe: Baseline to end of treatment (Day 28)

Population: The efficacy analysis set included all patients who were randomized (defined as having a randomization code recorded on the demography case report form), received at least one dose of study medication, and contributed sufficient data for at least one efficacy endpoint.

Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 is the volume expired in the first second of maximal expiration after a full inspiration.

Outcome measures

Measure	AZD5069 n=24 Participants AZD5069 80 mg bd	Placebo n=26 Participants Placebo bd
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)	-0.01 liters Standard Error 0.044	-0.01 liters Standard Error 0.043

SECONDARY outcome

Timeframe: Baseline to end of treatment (Day 28)

Population: The efficacy analysis set included all patients who were randomized (defined as having a randomization code recorded on the demography case report form), received at least one dose of study medication, and contributed sufficient data for at least one efficacy endpoint.

Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEF25-75 is flow rate during the middle half of forced vital capacity (25%-75% of the total volume (FVC) exhaled).

Outcome measures

Measure	AZD5069 n=24 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75)	-0.04 liters/second Standard Error 0.063	-0.07 liters/second Standard Error 0.062

SECONDARY outcome

Timeframe: Baseline to end of treatment (Day 28)

Population: The efficacy analysis set included all patients who were randomized (defined as having a randomization code recorded on the demography case report form), received at least one dose of study medication, and contributed sufficient data for at least one efficacy endpoint.

TDI measures changes in dyspnea severity from the baseline as established by the Baseline Dyspnea Index (BDI). TDI is an interviewer-administered rating of severity of dyspnea that assesses Change in Functional Impairment, Change in Magnitude of Task, and Change in Magnitude of Effort domains on a 7-point scale ranging from -3 (major deterioration) to +3 (major improvement). Total score ranges from -9 to +9. The lower the score, the more deterioration in severity of dyspnea.

Outcome measures

Measure	AZD5069 n=25 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Transition Dyspnea Index (TDI) at End of Treatment (Day 28)	-1 units on a scale Standard Error 0.5	-0 units on a scale Standard Error 0.5

SECONDARY outcome

Timeframe: Baseline and Last 7 days on treatment

Population: The efficacy analysis set included all patients who were randomized (defined as having a randomization code recorded on the demography case report form), received at least one dose of study medication, and contributed sufficient data for at least one efficacy endpoint.

The Bronkotest diary card is a paper based diary card that was filled out by patients daily, recording values from morning and evening peak expiratory flow (PEF) measurements and answering 8 questions on signs and symptoms. Summary statistics for baseline (mean of the last 7 days prior to first dose) and change (mean of the last 7 days on treatment - baseline) only contain patients included in the analysis. For symptom scores a decrease is an improvement, for PEF an increase is an improvement.

Outcome measures

Measure	AZD5069 n=26 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Change From Baseline for the Morning PEF and Evening PEF of the Bronkotest Diary Card Morning PEF	-5.3 L/min Standard Error 5.41	-5.9 L/min Standard Error 5.53
Change From Baseline for the Morning PEF and Evening PEF of the Bronkotest Diary Card Evening PEF	-7.3 L/min Standard Error 4.95	-10.6 L/min Standard Error 5.06

SECONDARY outcome

Timeframe: Baseline and Last 7 days on treatment

Population: The efficacy analysis set included all patients who were randomized (defined as having a randomization code recorded on the demography case report form), received at least one dose of study medication, and contributed sufficient data for at least one efficacy endpoint.

The Bronkotest diary card is a paper based diary card that was filled out by patients daily, recording values from morning and evening peak expiratory flow (PEF) measurements and answering 8 questions on signs and symptoms. Symptom scores were recorded for night-time symptoms, breathing, sputum colour, sputum amount, sputum type, wellbeing, number of puffs of inhalers, and cough, generally scored on a scale from 0 (no symptoms) to 4 (worst symptoms). Summary statistics for baseline (mean of the last 7 days prior to first dose) and change (mean of the last 7 days on treatment - baseline) only contain patients included in the analysis. For symptom scores a decrease is an improvement, for PEF an increase is an improvement.

Outcome measures

Measure	AZD5069 n=26 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Change From Baseline for the Symptom Scores of the Bronkotest Diary Card Night time symptom score	0.4 units on a scale Standard Error 0.12	0.1 units on a scale Standard Error 0.12
Change From Baseline for the Symptom Scores of the Bronkotest Diary Card Describe your breathing	0.1 units on a scale Standard Error 0.10	-0.1 units on a scale Standard Error 0.10
Change From Baseline for the Symptom Scores of the Bronkotest Diary Card How often do you cough?	0.1 units on a scale Standard Error 0.09	0.0 units on a scale Standard Error 0.09
Change From Baseline for the Symptom Scores of the Bronkotest Diary Card What color is your sputum?	-0.7 units on a scale Standard Error 0.18	-0.3 units on a scale Standard Error 0.18
Change From Baseline for the Symptom Scores of the Bronkotest Diary Card The amount of sputum you produced	0.1 units on a scale Standard Error 0.08	0.0 units on a scale Standard Error 0.09
Change From Baseline for the Symptom Scores of the Bronkotest Diary Card Type of sputum	-0.3 units on a scale Standard Error 0.09	-0.1 units on a scale Standard Error 0.09
Change From Baseline for the Symptom Scores of the Bronkotest Diary Card How do you feel?	0.2 units on a scale Standard Error 0.10	-0.0 units on a scale Standard Error 0.10
Change From Baseline for the Symptom Scores of the Bronkotest Diary Card Number of puffs of inhalers	0.1 units on a scale Standard Error 0.30	0.2 units on a scale Standard Error 0.30

SECONDARY outcome

Timeframe: Baseline and end of treatment (Day 28)

Population: The efficacy analysis set included all patients who were randomized (defined as having a randomization code recorded on the demography case report form), received at least one dose of study medication, and contributed sufficient data for at least one efficacy endpoint.

SGRQ-C total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). The SGRQ-C contains 3 domains:

Symptom (distress due to respiratory symptoms), Activity (disturbance of physical activity) and Impact (overall impact on daily life and well being). All three domains with scale from 0 (best health status) to 100 (worst possible status).

Outcome measures

Measure	AZD5069 n=25 Participants AZD5069 80 mg bd	Placebo n=26 Participants Placebo bd
Change From Baseline Total and Domain Scores in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total score	-1.75 units on a scale Standard Error 2.402	-0.09 units on a scale Standard Error 2.355
Change From Baseline Total and Domain Scores in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Symptom domain	-3.16 units on a scale Standard Error 2.356	1.72 units on a scale Standard Error 2.309
Change From Baseline Total and Domain Scores in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Activity domain	-0.46 units on a scale Standard Error 3.216	0.85 units on a scale Standard Error 3.153
Change From Baseline Total and Domain Scores in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Impact domain	-1.83 units on a scale Standard Error 2.742	-1.45 units on a scale Standard Error 2.689

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=22 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Ratio of Interleukin-1 Beta (IL-1β) in Sputum at End of Treatment Compared to Baseline	0.63 ratio Interval 0.44 to 0.9	0.91 ratio Interval 0.65 to 1.28

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=22 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Ratio of Interleukin-6 (IL-6) in Sputum at End of Treatment Compared to Baseline	3.68 ratio Interval 2.79 to 4.84	0.82 ratio Interval 0.64 to 1.07

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=22 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) in Sputum at End of Treatment Compared to Baseline	0.99 ratio Interval 0.79 to 1.24	1.07 ratio Interval 0.87 to 1.32

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=22 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) in Sputum at End of Treatment Compared to Baseline	0.91 ratio Interval 0.77 to 1.09	0.92 ratio Interval 0.78 to 1.08

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=22 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Ratio of Tumor Necrosis Factor Alpha (TNF-α) in Sputum at End of Treatment Compared to Baseline	1.29 ratio Interval 0.93 to 1.8	0.91 ratio Interval 0.67 to 1.23

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=22 Participants AZD5069 80 mg bd	Placebo n=25 Participants Placebo bd
Ratio of Growth-related Oncogene-α (GRO-α) in Sputum at End of Treatment Compared to Baseline	2.77 ratio Interval 2.08 to 3.67	0.85 ratio Interval 0.65 to 1.11

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=22 Participants AZD5069 80 mg bd	Placebo n=26 Participants Placebo bd
Ratio of Interleukin-8 (IL-8) in Sputum at End of Treatment Compared to Baseline	0.81 ratio Interval 0.62 to 1.07	0.80 ratio Interval 0.62 to 1.02

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=4 Participants AZD5069 80 mg bd	Placebo n=5 Participants Placebo bd
Ratio of Neutrophil Elastase Activity in Sputum at End of Treatment Compared to Baseline	0.34 ratio Interval 0.09 to 1.28	1.95 ratio Interval 0.59 to 6.39

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=24 Participants AZD5069 80 mg bd	Placebo n=24 Participants Placebo bd
Ratio of Serum Amyloid A (SAA) in Serum at End of Treatment Compared to Baseline	1.18 ratio Interval 0.82 to 1.72	0.89 ratio Interval 0.61 to 1.29

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=24 Participants AZD5069 80 mg bd	Placebo n=24 Participants Placebo bd
Ratio of C-reactive Protein (CRP) in Serum at End of Treatment Compared to Baseline	1.28 ratio Interval 0.94 to 1.76	0.83 ratio Interval 0.61 to 1.14

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=24 Participants AZD5069 80 mg bd	Placebo n=24 Participants Placebo bd
Ratio of Tumor Necrosis Factor Alpha (TNF-α) in Serum at End of Treatment Compared to Baseline	1.02 ratio Interval 0.97 to 1.06	0.97 ratio Interval 0.92 to 1.02

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=16 Participants AZD5069 80 mg bd	Placebo n=24 Participants Placebo bd
Ratio of Growth-related Oncogene-α (GRO-α) in Serum at End of Treatment Compared to Baseline	5.45 ratio Interval 4.42 to 6.73	0.99 ratio Interval 0.84 to 1.18

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=24 Participants AZD5069 80 mg bd	Placebo n=24 Participants Placebo bd
Ratio of Interleukin-6 (IL-6) in Serum at End of Treatment Compared to Baseline	1.13 ratio Interval 0.96 to 1.34	0.97 ratio Interval 0.82 to 1.15

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=24 Participants AZD5069 80 mg bd	Placebo n=24 Participants Placebo bd
Ratio of Interleukin-1 Beta (IL-1β) in Serum at End of Treatment Compared to Baseline	1.45 ratio Interval 1.25 to 1.67	0.93 ratio Interval 0.8 to 1.07

SECONDARY outcome

Timeframe: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Population: The PD analysis set comprised all patients who received at least 1 dose of study medication and for whom PD samples (absolute and percentage neutrophil cell count in sputum, sputum collection weight, inflammatory markers in sputum and serum) were available (assumed not to be affected by factors such as protocol violations).

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Outcome measures

Measure	AZD5069 n=24 Participants AZD5069 80 mg bd	Placebo n=24 Participants Placebo bd
Ratio of Interleukin-8 (IL-8) in Serum at End of Treatment Compared to Baseline	5.90 ratio Interval 4.74 to 7.34	0.97 ratio Interval 0.78 to 1.21

Adverse Events

AZD5069

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZD5069 n=26 participants at risk 80 mg bd	Placebo n=26 participants at risk Placebo for AZD5069 bd
Infections and infestations Infective Exacerbation Of Bronchiectasis	3.8% 1/26	0.00% 0/26

Other adverse events

Measure	AZD5069 n=26 participants at risk 80 mg bd	Placebo n=26 participants at risk Placebo for AZD5069 bd
Gastrointestinal disorders Diarrhoea	11.5% 3/26	0.00% 0/26
Gastrointestinal disorders Dyspepsia	7.7% 2/26	7.7% 2/26
Gastrointestinal disorders Vomiting	7.7% 2/26	0.00% 0/26
General disorders Non-Cardiac Chest Pain	7.7% 2/26	7.7% 2/26
Infections and infestations Nasopharyngitis	11.5% 3/26	19.2% 5/26
Infections and infestations Infective Exacerbation Of Bronchiectasis	3.8% 1/26	7.7% 2/26
Musculoskeletal and connective tissue disorders Back Pain	3.8% 1/26	7.7% 2/26
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	7.7% 2/26	3.8% 1/26
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/26	7.7% 2/26
Nervous system disorders Headache	19.2% 5/26	11.5% 3/26
Nervous system disorders Somnolence	0.00% 0/26	7.7% 2/26
Respiratory, thoracic and mediastinal disorders Cough	23.1% 6/26	3.8% 1/26
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	15.4% 4/26	3.8% 1/26
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/26	11.5% 3/26

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60