Trial Outcomes & Findings for Effect on Structural Changes in Airways, Measured by MSCT, of Twice Daily 60mg AZD9668 for 12 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT NCT01054170)

NCT ID: NCT01054170

Last Updated: 2012-08-20

Results Overview

AWT-Pi10 (mm) as a measure of structural changes in airways. End of treatment Least Squares Mean.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 52 participants
• Primary outcome timeframe: Measured after 12 weeks treatment (day 84)
• Results posted on: 2012-08-20

Participant Flow

First patient enrolled: 06 January 2010; Last patient completed: 17 November 2010; Twelve centres across 5 countries participated in this study: Canada (2), Denmark (3), The Netherlands (2), Romania (2) and Ukraine (3).

Tiotropium maintenance therapy and reliever medication were commenced at screening, except for patients on inhaled corticosteroids (ICS, ICS/LABA) who were required to stop these at enrolment and commence on tiotropium and reliever medication at the same time. These patients received tiotropium for a period of at least 3 weeks before screening.

Participant milestones

Measure	AZD9668 AZD9668 2x30mg bid	Placebo Placebo 2 tablets bid
Overall Study STARTED	25	27
Overall Study COMPLETED	21	21
Overall Study NOT COMPLETED	4	6

Reasons for withdrawal

Measure	AZD9668 AZD9668 2x30mg bid	Placebo Placebo 2 tablets bid
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	3	2
Overall Study Adverse Event	0	4

Baseline Characteristics

Effect on Structural Changes in Airways, Measured by MSCT, of Twice Daily 60mg AZD9668 for 12 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients

Baseline characteristics by cohort

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid	Total n=52 Participants Total of all reporting groups
Age Continuous	7.2 years STANDARD_DEVIATION 65 • n=5 Participants	7.7 years STANDARD_DEVIATION 66 • n=7 Participants	7.45 years STANDARD_DEVIATION 131 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	10 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

AWT-Pi10 (mm) as a measure of structural changes in airways. End of treatment Least Squares Mean.

Outcome measures

Measure	AZD9668 n=17 Participants AZD9668 2x30mg bid	Placebo n=19 Participants Placebo 2 tablets bid
AWT-Pi10 (Airway Wall Thickness of a Theoretical Airway With an Internal Perimeter of 10 mm)	3.84 mm Standard Error 0.021 • Interval 0.021 to	3.83 mm Standard Error 0.017 • Interval 0.017 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

5th Generation Wall Area Percentage as a measure of structural changes in airways. End of treatment Least Squares Mean.

Outcome measures

Measure	AZD9668 n=17 Participants AZD9668 2x30mg bid	Placebo n=19 Participants Placebo 2 tablets bid
5th Generation Wall Area Percentage	66.21 Percentage Area Standard Error 0.275 • Interval 0.275 to	65.94 Percentage Area Standard Error 0.234 • Interval 0.234 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

ATI Percentage as a measure of structural changes in airways. End of treatment Least Squares Mean.

Outcome measures

Measure	AZD9668 n=15 Participants AZD9668 2x30mg bid	Placebo n=13 Participants Placebo 2 tablets bid
Air Trapping Index (ATI) on Expiratory Scans	54.56 ATI Percentage Standard Error 1.706 • Interval 1.706 to	57.12 ATI Percentage Standard Error 1.599 • Interval 1.599 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Inspiratory Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668 2x30mg bid	Placebo n=23 Participants Placebo 2 tablets bid
Pre-bronchodilator Inspiratory Capacity (IC)	2.56 L Standard Error 0.154 • Interval 0.154 to	2.39 L Standard Error 0.153 • Interval 0.153 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Total Lung Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668 2x30mg bid	Placebo n=23 Participants Placebo 2 tablets bid
Pre-bronchodilator Total Lung Capacity (TLC)	7.03 L Standard Error 0.178 • Interval 0.178 to	6.92 L Standard Error 0.177 • Interval 0.177 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Functional Residual Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.

Outcome measures

Measure	AZD9668 n=23 Participants AZD9668 2x30mg bid	Placebo n=23 Participants Placebo 2 tablets bid
Pre-bronchodilator Functional Residual Capacity (FRC)	4.41 L Standard Error 0.165 • Interval 0.165 to	4.21 L Standard Error 0.158 • Interval 0.158 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Residual volume (L) as a measure of lung function. End of treatment Least Squares Mean.

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668 2x30mg bid	Placebo n=23 Participants Placebo 2 tablets bid
Pre-bronchodilator Residual Volume (RV)	3.64 L Standard Error 0.161 • Interval 0.161 to	3.73 L Standard Error 0.161 • Interval 0.161 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Specific Airway Conductance as a measure of lung function. End of treatment Least Squares Mean.

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668 2x30mg bid	Placebo n=23 Participants Placebo 2 tablets bid
Pre-bronchodilator Specific Airway Conductance (SGaw)	0.52 1/[s*kPa] Standard Error 0.034 • Interval 0.034 to	0.48 1/[s*kPa] Standard Error 0.034 • Interval 0.034 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Capacity of Carbon Monoxide as a measure of lung function. End of treatment Least Squares Mean.

Outcome measures

Measure	AZD9668 n=23 Participants AZD9668 2x30mg bid	Placebo n=23 Participants Placebo 2 tablets bid
Pre-bronchodilator Diffusion Capacity of Carbon Monoxide (DLco)	5.49 mmol/kPa*min Standard Error 0.204 • Interval 0.204 to	5.67 mmol/kPa*min Standard Error 0.209 • Interval 0.209 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid
Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	1.51 L Standard Error 0.048 • Interval 0.048 to	1.49 L Standard Error 0.050 • Interval 0.05 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

Outcome measures

Measure	AZD9668 n=21 Participants AZD9668 2x30mg bid	Placebo n=23 Participants Placebo 2 tablets bid
Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	1.60 L Standard Error 0.050 • Interval 0.05 to	1.58 L Standard Error 0.050 • Interval 0.05 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Forced Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid
Pre-bronchodilator Forced Vital Capacity (FVC)	3.25 L Standard Error 0.084 • Interval 0.084 to	3.14 L Standard Error 0.083 • Interval 0.083 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Forced Vital Capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

Outcome measures

Measure	AZD9668 n=21 Participants AZD9668 2x30mg bid	Placebo n=23 Participants Placebo 2 tablets bid
Post-bronchodilator Forced Vital Capacity (FVC)	3.34 L Standard Error 0.083 • Interval 0.083 to	3.34 L Standard Error 0.080 • Interval 0.08 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Slow Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid
Pre-bronchodilator Slow Vital Capacity (SVC)	3.42 L Standard Error 0.069 • Interval 0.069 to	3.38 L Standard Error 0.068 • Interval 0.068 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Slow Vital capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

Outcome measures

Measure	AZD9668 n=21 Participants AZD9668 2x30mg bid	Placebo n=23 Participants Placebo 2 tablets bid
Post-bronchodilator Slow Vital Capacity (SVC)	3.56 L Standard Error 0.063 • Interval 0.063 to	3.44 L Standard Error 0.061 • Interval 0.061 to

SECONDARY outcome

Timeframe: Average from measurements recorded daily by patient in last 6 weeks of treatment.

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning.

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid
Peak Expiratory Flow (PEF) Morning (Daily Recordings)	255.82 L/min Standard Error 9.956 • Interval 9.956 to	244.16 L/min Standard Error 9.871 • Interval 9.871 to

SECONDARY outcome

Timeframe: Average from measurements recorded daily by patient in last 6 weeks of treatment.

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each evening .

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid
Peak Expiratory Flow (PEF) Evening (Daily Recordings)	264.15 L/min Standard Error 10.02 • Interval 10.02 to	254.31 L/min Standard Error 9.966 • Interval 9.966 to

SECONDARY outcome

Timeframe: Average from measurements recorded daily by patient in last 6 weeks of treatment.

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning.

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid
Forced Expiratory Volume in 1 Second (FEV1) Morning (Daily Recordings)	1.49 L Standard Error 0.065 • Interval 0.065 to	1.29 L Standard Error 0.066 • Interval 0.066 to

SECONDARY outcome

Timeframe: Average from measurements recorded daily by patient in last 6 weeks of treatment.

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each evening.

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid
Forced Expiratory Volume in 1 Second (FEV1) Evening (Daily Recordings)	1.51 L Standard Error 0.062 • Interval 0.062 to	1.30 L Standard Error 0.064 • Interval 0.064 to

SECONDARY outcome

Timeframe: Average from measurements recorded daily by patient in last 6 weeks of treatment.

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Breathlessness, Cough and Sputum Scale, patient reported questionnaire as a measure of respiratory symptoms (reported on a 0 (best health status) to 12 (worst possible status) scale).

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid
Breathlessness, Cough and Sputum Scale (BCSS) Total Score	2.33 Total Score Standard Error 0.319 • Interval 0.319 to	3.36 Total Score Standard Error 0.301 • Interval 0.301 to

SECONDARY outcome

Timeframe: Average from measurements recorded daily by patient in last 6 weeks of treatment.

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

EXAcerbations of Chronic pulmonary disease Tool, patient questionnaire as a measure of respiratory symptoms (reported as units on a 0 (best health status) to 100 (worst possible status) scale).

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=26 Participants Placebo 2 tablets bid
EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score	28.48 Total Score Standard Error 2.065 • Interval 2.065 to	33.26 Total Score Standard Error 2.013 • Interval 2.013 to

SECONDARY outcome

Timeframe: Measured after 12 weeks treatment (day 84)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease, as a measure of Quality of Life (reported on a % scale from 0 (best health status) to 100(worst possible status)).

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=23 Participants Placebo 2 tablets bid
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Overall Score	35.64 Scores on a scale Standard Error 2.364 • Interval 2.364 to	39.61 Scores on a scale Standard Error 2.389 • Interval 2.389 to

SECONDARY outcome

Timeframe: Average from measurements recorded daily by patient in last 6 weeks of treatment.

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Percentage of reliever free days in last 6 weeks on treatment.

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid
Percentage of Reliever Free Days in Last Six Weeks of Treatment	34.23 percentage of days Standard Error 6.394 • Interval 6.394 to	26.43 percentage of days Standard Error 6.001 • Interval 6.001 to

SECONDARY outcome

Timeframe: Exacerbations were recorded at all study visits (after 1, 4, 8, and 12 weeks of treatment and at follow up)

Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Number of patients experiencing disease exacerbations on treatment.

Outcome measures

Measure	AZD9668 n=25 Participants AZD9668 2x30mg bid	Placebo n=27 Participants Placebo 2 tablets bid
Exacerbations	0 Participants	5 Participants

Adverse Events

AZD9668

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZD9668 n=25 participants at risk AZD9668 2x30mg bid	Placebo n=27 participants at risk Placebo 2 tablets bid
Injury, poisoning and procedural complications POST PROCEDURAL COMPLICATION	0.00% 0/25	3.7% 1/27

Other adverse events

Measure	AZD9668 n=25 participants at risk AZD9668 2x30mg bid	Placebo n=27 participants at risk Placebo 2 tablets bid
Gastrointestinal disorders DRY MOUTH	0.00% 0/25	7.4% 2/27
General disorders ASTHENIA	0.00% 0/25	7.4% 2/27
Infections and infestations NASOPHARYNGITIS	20.0% 5/25	7.4% 2/27
Nervous system disorders DIZZINESS	8.0% 2/25	0.00% 0/27
Respiratory, thoracic and mediastinal disorders COUGH	0.00% 0/25	11.1% 3/27
Respiratory, thoracic and mediastinal disorders BRONCHIAL WALL THICKENING	4.0% 1/25	7.4% 2/27
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.00% 0/25	7.4% 2/27

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