Efficacy and Safety of Twice Daily 60mg AZD9668 in COPD for 12 Weeks in Patients on Background Budesonide/Formoterol

A 12-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Multinational, Phase IIb Study to Evaluate the Efficacy and Safety of 60mg AZD9668 Administered Orally Twice Daily to Subjects With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Budesonide/Formoterol

The primary objective is to evaluate the efficacy of AZD9668 compared with placebo in symptomatic COPD patients by assessing the effects on lung function and symptoms of COPD

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 615
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Lovech, Bulgaria
    • Research Site
  • Pleven, Bulgaria
    • Research Site
  • Plovdiv, Bulgaria
    • Research Site
  • Russe, Bulgaria
    • Research Site
  • Sofia, Bulgaria
    • Research Site
  • Stara Zagora, Bulgaria
    • Research Site
  • Troyan, Bulgaria
    • Research Site
  • Varna, Bulgaria
    • Research Site
• Czech Republic
  • Jihlava, Czech Republic
    • Research Site
  • Jindrichuv Hradec, Czech Republic
    • Research Site
  • Kladno, Czech Republic
    • Research Site
  • Krnov, Czech Republic
    • Research Site
  • Novy Jicin, Czech Republic
    • Research Site
  • Pardubice, Czech Republic
    • Research Site
  • Praha 10, Czech Republic
    • Research Site
  • Praha 5, Czech Republic
    • Research Site
  • Rokycany, Czech Republic
    • Research Site
  • Trebic, Czech Republic
    • Research Site
• Hungary
  • Balassagyarmat, Hungary
    • Research Site
  • Budapest, Hungary
    • Research Site
  • Debrecen, Hungary
    • Research Site
  • Deszk, Hungary
    • Research Site
  • Gyor, Hungary
    • Research Site
  • Nyiregyhaza, Hungary
    • Research Site
  • Pecs, Hungary
    • Research Site
  • Szazhalombatta, Hungary
    • Research Site
  • Szombathely, Hungary
    • Research Site
  • Torokbalint, Hungary
    • Research Site
  • Vasarosnameny, Hungary
    • Research Site
• Poland
  • Bialystok, Poland
    • Research Site
  • Gdynia, Poland
    • Research Site
  • Gorzow Wlkp, Poland
    • Research Site
  • Grodzisk Mazowiecki, Poland
    • Research Site
  • Jelenia Gora, Poland
    • Research Site
  • Katowice, Poland
    • Research Site
  • Kielce, Poland
    • Research Site
  • Krakow, Poland
    • Research Site
  • Lodz, Poland
    • Research Site
  • Lublin, Poland
    • Research Site
  • Pila, Poland
    • Research Site
  • Skierniewice, Poland
    • Research Site
  • Szczecin, Poland
    • Research Site
  • Tarnow, Poland
    • Research Site
  • Warszawa, Poland
    • Research Site
  • Wroclaw, Poland
    • Research Site
• Romania
  • Bucharest, Romania
    • Research Site
  • Bucuresti, Romania
    • Research Site
  • Constanta, Romania
    • Research Site
  • Iasi, Romania
    • Research Site
  • Hunedoara
    • Deva, Hunedoara, Romania
      • Research Site
• Slovakia
  • Bardejov, Slovakia
    • Research Site
  • Bojnice, Slovakia
    • Research Site
  • Bratislava, Slovakia
    • Research Site
  • Dunajska Streda, Slovakia
    • Research Site
  • Humenne, Slovakia
    • Research Site
  • Kosice, Slovakia
    • Research Site
  • Liptovsky Hradok, Slovakia
    • Research Site
  • Nove Mesto Nad Vahom, Slovakia
    • Research Site
  • Nove Zamky, Slovakia
    • Research Site
  • Poprad, Slovakia
    • Research Site
  • Povazska Bystrica, Slovakia
    • Research Site
  • Presov, Slovakia
    • Research Site
  • Revuca, Slovakia
    • Research Site
  • Spisska Nova Ves, Slovakia
    • Research Site
  • Trnava, Slovakia
    • Research Site
  • Trstena, Slovakia
    • Research Site
  • Zilina, Slovakia
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 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 >= 30 and < 80 % of predicted post-bronchodilator
• Symptomatic COPD for a total of 7 days in the two weeks prior to randomisation
• At least 1 COPD exacerbation from 4 weeks to 12 months before the screening visit

Exclusion Criteria:

• Past history or current evidence of clinically significant heart disease
• Current diagnosis of asthma
• Patients who require long term oxygen therapy
• Worsening of COPD requiring treatment with antibiotics, 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
Experimental: 1	Drug: AZD9668; 2 x 30 mg oral tablets bd for 12 weeks
Placebo Comparator: 2	Drug: Placebo; 2 x matched placebo to oral tablet bd for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Pre-bronchodilator FEV1 (L)	Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.	Day 1
End-value Pre-bronchodilator FEV1 (L)	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)	up to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-bronchodilator FEV1 (L) - Baseline	Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic.	Day 1
Post-bronchodilator FEV1 (L) - End-value	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)	up to week 12
Pre-bronchodilator FVC (L) - Baseline	Forced vital capacity (FVC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.	Day 1
Pre-bronchodilator FVC (L) - End-value	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)	up to week 12
Post-bronchodilator FVC (L) - Baseline	Forced vital capacity (FVC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic.	Day 1
Post-bronchodilator FVC (L) - End-value	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)	up to week 12
Baseline Pre-bronchodilator FEV6 (L)	Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.	Day 1
End-value Pre-bronchodilator FEV6 (L)	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)	up to week 12
Baseline Post-bronchodilator FEV6 (L)	Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured post after bronchodilator (salbutamol) use in the clinic.	Day 1
End-value Post-bronchodilator FEV6 (L)	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)	up to week 12
Baseline Pre-bronchodilator FEF25-75% (L/Sec)	Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.	Day 1
End-value Pre-bronchodilator FEF25-75% (L/Sec)	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)	up to week 12
Baseline Post-bronchodilator FEF25-75% (L/Sec)	Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic.	Day 1
End-value Post-bronchodilator FEF25-75% (L/Sec)	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)	up to week 12
Pre-bronchodilator IC (L) - Baseline	Inspiratory capacity (IC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.	Day 1
Pre-bronchodilator IC (L) - End-value	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)	up to week 12
Post-bronchodilator IC (L) - Baseline	Inspiratory capacity (IC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic.	Day 1
Post-bronchodilator IC (L) - End-value	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)	up to week 12
PEF - Baseline Measured by Patient at Home (L/Min) in the Morning	Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning. Baseline is the mean of last 10 days of data before start of treatment.	Baseline
PEF - End-value Measured by Patient at Home (L/Min) in the Morning	Peak expiratory flow (PEF)	Last 6 weeks on treatment
FEV1 - Baseline Measured by Patient at Home (L) in the Morning	Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning. Baseline is the mean of last 10 days of data before start of treatment.	Baseline
FEV1 - End-value Measured by Patient at Home (L) in the Morning	Forced Expiratory Volume in 1 second (L)	Last 6 weeks on treatment
EXACT - Baseline 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). Baseline is the mean of last 10 days of data before start of treatment.	Baseline
EXACT - End-value 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).	Last 6 weeks on treatment
BCSS - Baseline 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). Baseline is the mean of last 10 days of data before start of treatment.	Baseline
BCSS - End-value 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).	Last 6 weeks on treatment
Sputum Colour - Baseline	Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status).	Baseline
Sputum Colour - End Value	Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status). End of treatment week 12	End of treatment week 12
Use of Reliever Medication	Daily average of number of inhalations of reliever medication	Last 6 weeks on treatment
Incremental Shuttle Walk Test - Baseline	Endurance time (s)	Day 1
Incremental Shuttle Walk Test - End Value		Week 12 - visit 6
Endurance Shuttle Walk Test - Baseline	Endurance time (s)	Day 1
Endurance Shuttle Walk Test - End Value	Assessed at vist 6 -( last on treatment clinic visit)	Week 12 - visit 6
St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline	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)).	Day 1
St George's Respiratory Questionnaire (COPD) - End-value 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)).Questionaire assessed on vist 6 -( last on treatment clinic visit)	Measured Day 1 and 12 weeks
Exacerbations - Clinic Defined	Number of patients having a clinic defined disease exacerbation.	Duration of the the treatment period - 12 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Piotr Kuna, Professor, Samodzielny Publiczny ZOZ Uniwersytecki Szpital Kliniczny

Publications and helpful links

General Publications

• Leidy NK, Murray LT, Monz BU, Nelsen L, Goldman M, Jones PW, Dansie EJ, Sethi S. Measuring respiratory symptoms of COPD: performance of the EXACT- Respiratory Symptoms Tool (E-RS) in three clinical trials. Respir Res. 2014 Oct 7;15(1):124. doi: 10.1186/s12931-014-0124-z.
• Leidy NK, Murray LT, Jones P, Sethi S. Performance of the EXAcerbations of chronic pulmonary disease tool patient-reported outcome measure in three clinical trials of chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2014 Mar;11(3):316-25. doi: 10.1513/AnnalsATS.201309-305OC.
• Kuna P, Jenkins M, O'Brien CD, Fahy WA. AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in patients with COPD. Respir Med. 2012 Apr;106(4):531-9. doi: 10.1016/j.rmed.2011.10.020. Epub 2011 Dec 23.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: December 1, 2009
• First Submitted That Met QC Criteria: December 1, 2009
• First Posted (Estimate): December 2, 2009

Study Record Updates

• Last Update Posted (Estimate): August 3, 2012
• Last Update Submitted That Met QC Criteria: June 19, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: lung; COPD; efficacy; Chronic; respiratory disease; placebo-controlled; FEV1; obstructive; pulmonary; St Georges Respiratory Questionnaire
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D0520C00020