Trial Outcomes & Findings for 14729-D9831C00002- 1 Month Biopsy Study (NCT NCT00766415)

NCT ID: NCT00766415

Last Updated: 2014-02-28

Results Overview

Composite endpoint subscores: histological grade, immunohistochemistry grade, leucocyte counts. Each subscore measured on scale 1 (normal) to 5 (worst outcome). Composite score summed across the subscores, ranging from 3 (normal) to 15 (worst outcome). Change from baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 52 participants
• Primary outcome timeframe: Before and after 1 month treatment
• Results posted on: 2014-02-28

Participant Flow

84 patients enrolled, 52 were randomised, 1 patient discontinued before treatment start and 51 patients completed the study. First patient entered the study on 17 November 2008 and the last patient finished the study on 10 June 2009.

Participant milestones

Measure	AZD1981 AZD1981 1000 mg, twice daily	Placebo Placebo, twice daily
Overall Study STARTED	25	27
Overall Study COMPLETED	25	26
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	AZD1981 AZD1981 1000 mg, twice daily	Placebo Placebo, twice daily
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

14729-D9831C00002- 1 Month Biopsy Study

Baseline characteristics by cohort

Measure	AZD1981 n=25 Participants AZD1981 1000 mg, twice daily	Placebo n=26 Participants Placebo, twice daily	Total n=51 Participants Total of all reporting groups
Age, Continuous	61 Years n=5 Participants	61.1 Years n=7 Participants	61 Years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	22 Participants n=7 Participants	38 Participants n=5 Participants

PRIMARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Composite endpoint subscores: histological grade, immunohistochemistry grade, leucocyte counts. Each subscore measured on scale 1 (normal) to 5 (worst outcome). Composite score summed across the subscores, ranging from 3 (normal) to 15 (worst outcome). Change from baseline.

Outcome measures

Measure	AZD1981 n=24 Participants AZD1981 1000 mg, twice daily	Placebo n=26 Participants Placebo, twice daily
Aggregated Pathology Score	7.88 Score on a scale 95% Confidence Interval 7.43 • Interval 7.43 to 8.34	8.15 Score on a scale 95% Confidence Interval 7.68 • Interval 7.68 to 8.63

PRIMARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Bronchoalveolar Lavage (BAL): Eosinophil count (% of total) from baseline

Outcome measures

Measure	AZD1981 n=21 Participants AZD1981 1000 mg, twice daily	Placebo n=22 Participants Placebo, twice daily
Bronchoalveolar Lavage (BAL): Eosinophil Count (%)	-1.58 percentage 95% Confidence Interval -2.22 • Interval -2.22 to -0.94	-1.45 percentage 95% Confidence Interval -2.13 • Interval -2.13 to -0.78

PRIMARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Bronchoalveolar Lavage (BAL): Neutrophil count (% of total) from baseline

Outcome measures

Measure	AZD1981 n=21 Participants AZD1981 1000 mg, twice daily	Placebo n=22 Participants Placebo, twice daily
Bronchoalveolar Lavage (BAL): Neutrophil Count (%)	-2.24 percentage 95% Confidence Interval -12.94 • Interval -12.94 to 8.46	-5.67 percentage 95% Confidence Interval -16.75 • Interval -16.75 to 5.42

PRIMARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Bronchoalveolar Lavage (BAL): Macrophages count (% of total) from baseline

Outcome measures

Measure	AZD1981 n=21 Participants AZD1981 1000 mg, twice daily	Placebo n=22 Participants Placebo, twice daily
Bronchoalveolar Lavage (BAL): Macrophages Count (%)	9.84 percentage 95% Confidence Interval -1.51 • Interval -1.51 to 21.2	10.68 percentage 95% Confidence Interval -1.24 • Interval -1.24 to 22.6

PRIMARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Bronchoalveolar Lavage (BAL): Lymphocytes count (% of total) from baseline

Outcome measures

Measure	AZD1981 n=21 Participants AZD1981 1000 mg, twice daily	Placebo n=22 Participants Placebo, twice daily
Bronchoalveolar Lavage (BAL): Lymphocytes Count (%)	-1.47 percentage 95% Confidence Interval -3.04 • Interval -3.04 to 0.11	-0.37 percentage 95% Confidence Interval -2.02 • Interval -2.02 to 1.28

PRIMARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Bronchoalveolar Lavage (BAL): Epithelial cells count (% of total) from baseline

Outcome measures

Measure	AZD1981 n=21 Participants AZD1981 1000 mg, twice daily	Placebo n=22 Participants Placebo, twice daily
Bronchoalveolar Lavage (BAL): Epithelial Cells Count (%)	-4.18 percentage 95% Confidence Interval -11.80 • Interval -11.8 to 3.45	-2.98 percentage 95% Confidence Interval -10.98 • Interval -10.98 to 5.01

PRIMARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Bronchoalveolar Lavage (BAL): Total cells count from baseline

Outcome measures

Measure	AZD1981 n=23 Participants AZD1981 1000 mg, twice daily	Placebo n=24 Participants Placebo, twice daily
Bronchoalveolar Lavage (BAL): Total Cells Count	0.02 10^6/g 95% Confidence Interval -0.10 • Interval -0.1 to 0.15	0.04 10^6/g 95% Confidence Interval -0.10 • Interval -0.1 to 0.17

PRIMARY outcome

Timeframe: Before and after 3 week treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Induced sputum Eosinophil count (% of total) from baseline

Outcome measures

Measure	AZD1981 n=14 Participants AZD1981 1000 mg, twice daily	Placebo n=17 Participants Placebo, twice daily
Induced Sputum: Eosinophil Count (%)	-2.14 percentage 95% Confidence Interval -3.30 • Interval -3.3 to -0.98	-0.81 percentage 95% Confidence Interval -1.92 • Interval -1.92 to 0.3

PRIMARY outcome

Timeframe: Before and after 3 week treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Induced sputum Neutrophils count (% of total) from baseline

Outcome measures

Measure	AZD1981 n=14 Participants AZD1981 1000 mg, twice daily	Placebo n=17 Participants Placebo, twice daily
Induced Sputum: Neutrophils Count (%)	0.70 percentage 95% Confidence Interval -12.79 • Interval -12.79 to 14.19	3.73 percentage 95% Confidence Interval -8.84 • Interval -8.84 to 16.3

PRIMARY outcome

Timeframe: Before and after 3 week treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Induced sputum Macrophages count (% of total) from baseline

Outcome measures

Measure	AZD1981 n=14 Participants AZD1981 1000 mg, twice daily	Placebo n=17 Participants Placebo, twice daily
Induced Sputum: Macrophages Count (%)	1.31 percentage 95% Confidence Interval -11.95 • Interval -11.95 to 14.57	-7.79 percentage 95% Confidence Interval -20.27 • Interval -20.27 to 4.69

PRIMARY outcome

Timeframe: Before and after 3 week treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Induced sputum Lymphocytes count (% of total) from baseline

Outcome measures

Measure	AZD1981 n=14 Participants AZD1981 1000 mg, twice daily	Placebo n=17 Participants Placebo, twice daily
Induced Sputum: Lymphocytes Count (%)	-0.01 percentage 95% Confidence Interval -0.21 • Interval -0.21 to 0.18	0.02 percentage 95% Confidence Interval -0.17 • Interval -0.17 to 0.2

PRIMARY outcome

Timeframe: Before and after 3 week treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Induced sputum Epithelial cells count (% of total) from baseline

Outcome measures

Measure	AZD1981 n=14 Participants AZD1981 1000 mg, twice daily	Placebo n=17 Participants Placebo, twice daily
Induced Sputum: Epithelial Cells Count (%)	-0.50 percentage 95% Confidence Interval -6.01 • Interval -6.01 to 5.01	4.11 percentage 95% Confidence Interval -1.04 • Interval -1.04 to 9.27

PRIMARY outcome

Timeframe: Before and after 3 week treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Induced sputum Total cells count from baseline

Outcome measures

Measure	AZD1981 n=19 Participants AZD1981 1000 mg, twice daily	Placebo n=17 Participants Placebo, twice daily
Induced Sputum: Total Cells Count	-1.07 10^6/g 95% Confidence Interval -3.21 • Interval -3.21 to 1.08	-1.69 10^6/g 95% Confidence Interval -4.07 • Interval -4.07 to 0.69

SECONDARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in Forced Expiratory Volume in 1 second (FEV1) from baseline to end of treatment

Outcome measures

Measure	AZD1981 n=25 Participants AZD1981 1000 mg, twice daily	Placebo n=26 Participants Placebo, twice daily
Forced Expiratory Volume in 1 Second (FEV1)	-4.77 percentage change 95% Confidence Interval -15.94 • Interval -15.94 to 6.4	6.16 percentage change 95% Confidence Interval -5.66 • Interval -5.66 to 17.97

SECONDARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Change in total CCQ score from baseline to last measurement on treatment. scored on a scale of 0 - 6. 0 =(low symptoms)-6 =(high symptoms)

Outcome measures

Measure	AZD1981 n=25 Participants AZD1981 1000 mg, twice daily	Placebo n=24 Participants Placebo, twice daily
Clinical Chronic Obstructive Pulmonary Disease (COPD) The Clinical COPD Questionnaire (CCQ)	-0.38 Scores on a scale 95% Confidence Interval -0.69 • Interval -0.69 to -0.06	-0.34 Scores on a scale 95% Confidence Interval -0.68 • Interval -0.68 to 0.0

SECONDARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean change in Peak Expiratory Flow (PEF) morning from baseline to the average of the treatment period

Outcome measures

Measure	AZD1981 n=25 Participants AZD1981 1000 mg, twice daily	Placebo n=24 Participants Placebo, twice daily
Peak Expiratory Flow (PEF) Morning	2.57 L/min 95% Confidence Interval -9.55 • Interval -9.55 to 14.69	-4.14 L/min 95% Confidence Interval -16.96 • Interval -16.96 to 8.69

SECONDARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean change in Peak Expiratory Flow (PEF) evening from baseline to the average of the treatment period

Outcome measures

Measure	AZD1981 n=25 Participants AZD1981 1000 mg, twice daily	Placebo n=21 Participants Placebo, twice daily
Peak Expiratory Flow (PEF) Evening	1.31 L/min 95% Confidence Interval -13.03 • Interval -13.03 to 15.65	1.46 L/min 95% Confidence Interval -14.27 • Interval -14.27 to 17.19

SECONDARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean change in COPD symptom night-time awakening score from baseline to the average of the treatment period. 0=(no symptom)-4=(no sleep)

Outcome measures

Measure	AZD1981 n=25 Participants AZD1981 1000 mg, twice daily	Placebo n=24 Participants Placebo, twice daily
Chronic Obstructive Pulmonary Disease (COPD) Symptom Night-time Awakenings Score	-0.23 Score on a scale 95% Confidence Interval -0.47 • Interval -0.47 to 0.01	-0.24 Score on a scale 95% Confidence Interval -0.49 • Interval -0.49 to 0.02

SECONDARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean change in COPD symptom breathing score from baseline to the average of the treatment period. 0= (none) - 4 =(severe).

Outcome measures

Measure	AZD1981 n=25 Participants AZD1981 1000 mg, twice daily	Placebo n=21 Participants Placebo, twice daily
Chronic Obstructive Pulmonary Disease (COPD) Symptom Breathing Score	-0.25 Score on a scale 95% Confidence Interval -0.47 • Interval -0.47 to -0.03	-0.21 Score on a scale 95% Confidence Interval -0.45 • Interval -0.45 to 0.04

SECONDARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean change in COPD symptom cough score from baseline to the average of the treatment period. 0= (none) - 4= (almost constant)

Outcome measures

Measure	AZD1981 n=25 Participants AZD1981 1000 mg, twice daily	Placebo n=21 Participants Placebo, twice daily
Chronic Obstructive Pulmonary Disease (COPD) Symptom Cough Score	-0.39 Score on a scale 95% Confidence Interval -0.63 • Interval -0.63 to -0.16	-0.35 Score on a scale 95% Confidence Interval -0.61 • Interval -0.61 to -0.09

SECONDARY outcome

Timeframe: Before and after 1 month treatment

Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.

Mean change in COPD symptom sputum score from baseline to the average of the treatment period. 0= (none) - 4= (severe).

Outcome measures

Measure	AZD1981 n=25 Participants AZD1981 1000 mg, twice daily	Placebo n=21 Participants Placebo, twice daily
Chronic Obstructive Pulmonary Disease (COPD) Symptom Sputum Score	-0.32 Score on a scale 95% Confidence Interval -0.52 • Interval -0.52 to -0.12	-0.38 Score on a scale 95% Confidence Interval -0.60 • Interval -0.6 to -0.16

SECONDARY outcome

Timeframe: 1 month

Number of participants with an Adverse Event

Outcome measures

Measure	AZD1981 n=25 Participants AZD1981 1000 mg, twice daily	Placebo n=26 Participants Placebo, twice daily
Adverse Event (AE)	17 Participants	14 Participants

Adverse Events

AZD1981

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZD1981 n=25 participants at risk AZD1981 1000 mg, twice daily	Placebo n=26 participants at risk Placebo, twice daily
Respiratory, thoracic and mediastinal disorders Hypoxia After Bronchoscopy	4.0% 1/25 1 participant discontinued immediately following randomization, did not start treatment and have not been included in any of the efficacy or safety calculations.	0.00% 0/26 1 participant discontinued immediately following randomization, did not start treatment and have not been included in any of the efficacy or safety calculations.

Other adverse events

Measure	AZD1981 n=25 participants at risk AZD1981 1000 mg, twice daily	Placebo n=26 participants at risk Placebo, twice daily
Infections and infestations Nasopharyngitis	12.0% 3/25 1 participant discontinued immediately following randomization, did not start treatment and have not been included in any of the efficacy or safety calculations.	7.7% 2/26 1 participant discontinued immediately following randomization, did not start treatment and have not been included in any of the efficacy or safety calculations.
Nervous system disorders Headache	4.0% 1/25 1 participant discontinued immediately following randomization, did not start treatment and have not been included in any of the efficacy or safety calculations.	11.5% 3/26 1 participant discontinued immediately following randomization, did not start treatment and have not been included in any of the efficacy or safety calculations.
Musculoskeletal and connective tissue disorders Back Pain	4.0% 1/25 1 participant discontinued immediately following randomization, did not start treatment and have not been included in any of the efficacy or safety calculations.	7.7% 2/26 1 participant discontinued immediately following randomization, did not start treatment and have not been included in any of the efficacy or safety calculations.

Additional Information

Alison Holt

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

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

Restriction type: LTE60