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

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.

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)

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: AZD9668; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada
    • Research Site
  • Ontario
    • Kingston, Ontario, Canada
      • Research Site
• Denmark
  • Hellerup, Denmark
    • Research Site
  • Hvidovre, Denmark
    • Research Site
  • Odensec, Denmark
    • Research Site
• Netherlands
  • Breda, Netherlands
    • Research Site
  • Nieuwegein, Netherlands
    • Research Site
• Romania
  • Bucuresti, Romania
    • Research Site
• Ukraine
  • Kyiv, Ukraine
    • Research Site

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Professor Asger Dirksen, Gentofte Hospital, Department of Lung Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: January 20, 2010
• First Submitted That Met QC Criteria: January 21, 2010
• First Posted (Estimate): January 22, 2010

Study Record Updates

• Last Update Posted (Estimate): August 20, 2012
• Last Update Submitted That Met QC Criteria: August 14, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: lung; COPD; efficacy; Chronic; respiratory disease; placebo-controlled; FEV1; Computed Tomography; obstructive; pulmonary; MSCT; St Georges Respiratory Questionnaire
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D0520C00014