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

• ClinicalTrials.gov Identifier: NCT01054170
• Recruitment Status: Completed
• First Posted: January 22, 2010
• Results First Posted: July 25, 2012
• Last Update Posted: August 20, 2012
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

The primary objective of the study is to evaluate structural changes effected by AD9668 in the airways of adults with Chronic Obstructive Pulmonary Disease (COPD) by Multi-Slice Computed Tomography (MSCT)

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: AZD9668; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 12-week, Phase II, Double-blind, Placebo-Controlled, Randomised, Parallel-Group, Multi-Centre Study to Assess the Effect of 60mg AZD9668 Administered Orally Twice Daily on Structural Changes in the Airways by Multi-Slice Computed Tomography in Patients With Chronic Obstructive Pulmonary Disease.
• Study Start Date: January 2010
• Actual Primary Completion Date: November 2010
• Actual Study Completion Date: November 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: AZD9668	Drug: AZD9668; 2 x 30 mg oral tablets twice daily (bid) for 12 weeks
Placebo Comparator: Placebo	Drug: Placebo; 2 x matched placebo to oral tablet twice daily (bid) for 12 weeks

Outcome Measures

Primary Outcome Measures :

1. AWT-Pi10 (Airway Wall Thickness of a Theoretical Airway With an Internal Perimeter of 10 mm) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
   AWT-Pi10 (mm) as a measure of structural changes in airways. End of treatment Least Squares Mean.

Secondary Outcome Measures :

1. 5th Generation Wall Area Percentage [ Time Frame: Measured after 12 weeks treatment (day 84) ]
   5th Generation Wall Area Percentage as a measure of structural changes in airways. End of treatment Least Squares Mean.
2. Air Trapping Index (ATI) on Expiratory Scans [ Time Frame: Measured after 12 weeks treatment (day 84) ]
   ATI Percentage as a measure of structural changes in airways. End of treatment Least Squares Mean.
3. Pre-bronchodilator Inspiratory Capacity (IC) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
   Inspiratory Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.
4. Pre-bronchodilator Total Lung Capacity (TLC) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
   Total Lung Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.
5. Pre-bronchodilator Functional Residual Capacity (FRC) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
   Functional Residual Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.
6. Pre-bronchodilator Residual Volume (RV) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
   Residual volume (L) as a measure of lung function. End of treatment Least Squares Mean.
7. Pre-bronchodilator Specific Airway Conductance (SGaw) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
   Specific Airway Conductance as a measure of lung function. End of treatment Least Squares Mean.
8. Pre-bronchodilator Diffusion Capacity of Carbon Monoxide (DLco) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
   Capacity of Carbon Monoxide as a measure of lung function. End of treatment Least Squares Mean.
9. Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
   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).
10. Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
    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).
11. Pre-bronchodilator Forced Vital Capacity (FVC) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
    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).
12. Post-bronchodilator Forced Vital Capacity (FVC) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
    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).
13. Pre-bronchodilator Slow Vital Capacity (SVC) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
    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).
14. Post-bronchodilator Slow Vital Capacity (SVC) [ Time Frame: Measured after 12 weeks treatment (day 84) ]
    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).
15. Peak Expiratory Flow (PEF) Morning (Daily Recordings) [ Time Frame: Average from measurements recorded daily by patient in last 6 weeks of treatment. ]
    Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning.
16. Peak Expiratory Flow (PEF) Evening (Daily Recordings) [ Time Frame: Average from measurements recorded daily by patient in last 6 weeks of treatment. ]
    Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each evening .
17. Forced Expiratory Volume in 1 Second (FEV1) Morning (Daily Recordings) [ Time Frame: Average from measurements recorded daily by patient in last 6 weeks of treatment. ]
    Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning.
18. Forced Expiratory Volume in 1 Second (FEV1) Evening (Daily Recordings) [ Time Frame: Average from measurements recorded daily by patient in last 6 weeks of treatment. ]
    Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each evening.
19. Breathlessness, Cough and Sputum Scale (BCSS) Total Score [ Time Frame: Average from measurements recorded daily by patient in last 6 weeks of treatment. ]
    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).
20. EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score [ Time Frame: Average from measurements recorded daily by patient in last 6 weeks of treatment. ]
    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).
21. St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Overall Score [ Time Frame: Measured after 12 weeks treatment (day 84) ]
    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)).
22. Percentage of Reliever Free Days in Last Six Weeks of Treatment [ Time Frame: Average from measurements recorded daily by patient in last 6 weeks of treatment. ]
    Percentage of reliever free days in last 6 weeks on treatment.
23. Exacerbations [ Time Frame: Exacerbations were recorded at all study visits (after 1, 4, 8, and 12 weeks of treatment and at follow up) ]
    Number of patients experiencing disease exacerbations on treatment.

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of COPD with symptoms over 1 year
• FEV1/FVC < 70% and FEV1 >= 40 and < =70 % of predicted post-bronchodilator
• Ex-smokers for at least 12 months

Exclusion Criteria:

• Past history or current evidence of clinically significant heart disease
• Current diagnosis of asthma
• Worsening of COPD requiring hospitalisation and/or treatment with antibiotics and/or an increase in inhaled steroid dose and/or oral steroids within 4 weeks of study visit 1b

Contacts and Locations

Locations

Canada, Ontario

Research Site

Kingston, Ontario, Canada

Canada

Research Site

Quebec, Canada

Denmark

Research Site

Hellerup, Denmark

Research Site

Hvidovre, Denmark

Research Site

Odensec, Denmark

Netherlands

Research Site

Breda, Netherlands

Research Site

Nieuwegein, Netherlands

Romania

Research Site

Bucuresti, Romania

Ukraine

Research Site

Kyiv, Ukraine

Sponsors and Collaborators

AstraZeneca

Investigators

• Principal Investigator: Professor Asger Dirksen; Gentofte Hospital, Department of Lung Medicine

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nordenmark LH, Taylor R, Jorup C. Feasibility of Computed Tomography in a Multicenter COPD Trial: A Study of the Effect of AZD9668 on Structural Airway Changes. Adv Ther. 2015 Jun;32(6):548-66. doi: 10.1007/s12325-015-0215-3. Epub 2015 Jun 5.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01054170
• Other Study ID Numbers: D0520C00014
• First Posted: January 22, 2010
• Results First Posted: July 25, 2012
• Last Update Posted: August 20, 2012
• Last Verified: August 2012

Keywords provided by AstraZeneca:

Chronic; obstructive; pulmonary; lung; respiratory disease; efficacy; placebo-controlled; COPD; FEV1; St Georges Respiratory Questionnaire; Computed Tomography; MSCT

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases