A Dose Range Finding Study to Evaluate the Efficacy and Safety of AZD9668 Administered Orally at Three Dose Levels to Patients With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Tiotropium

A 12-week, Randomised, Double-blind, Placebo-controlled, Parallel Group, Multinational, Phase IIb Dose Range Finding Study to Evaluate the Efficacy and Safety of AZD9668 Administered Orally at 3 Dose Levels to Patients With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Tiotropium

The primary objective is to evaluate the dose-response relationship and efficacy of AZD9668 at 3 dose levels compared with placebo in symptomatic COPD patients by assessing effects on lung function and symptoms of COPD.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 838
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia
      • Research Site
    • Glebe, New South Wales, Australia
      • Research Site
    • Kogarah, New South Wales, Australia
      • Research Site
  • Queensland
    • Carina Heights, Queensland, Australia
      • Research Site
  • South Australia
    • Adelaide, South Australia, Australia
      • Research Site
    • Daw Park, South Australia, Australia
      • Research Site
  • Victoria
    • Parkville, Victoria, Australia
      • Research Site
  • Western Australia
    • Nedlands, Western Australia, Australia
      • Research Site
• Canada
  • Quebec, Canada
    • Research Site
  • Alberta
    • Edmonton, Alberta, Canada
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Research Site
  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada
      • Research Site
  • Nova Scotia
    • Antigonish, Nova Scotia, Canada
      • Research Site
  • Ontario
    • Grimsby, Ontario, Canada
      • Research Site
    • Hamilton, Ontario, Canada
      • Research Site
    • Kingston, Ontario, Canada
      • Research Site
    • Mississauga, Ontario, Canada
      • Research Site
    • Toronto, Ontario, Canada
      • Research Site
  • Quebec
    • La Malbaie, Quebec, Canada
      • Research Site
    • Mirabel, Quebec, Canada
      • Research Site
    • Saint-leonard, Quebec, Canada
      • Research Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • Research Site
• Germany
  • Berlin, Germany
    • Research Site
  • Fulda, Germany
    • Research Site
  • Hannover, Germany
    • Research Site
  • Leipzig, Germany
    • Research Site
  • Marburg, Germany
    • Research Site
• Japan
  • Bunkyo, Japan
    • Research Site
  • Fukuoka, Japan
    • Research Site
  • Hiroshima, Japan
    • Research Site
  • Kagoshima, Japan
    • Research Site
  • Kochi, Japan
    • Research Site
  • Aichi
    • Seto, Aichi, Japan
      • Research Site
  • Chiba
    • Noda, Chiba, Japan
      • Research Site
  • Ehime
    • Touon, Ehime, Japan
      • Research Site
  • Fukuoka
    • Yukuhashi, Fukuoka, Japan
      • Research Site
  • Fukushima
    • Nihonmatsu, Fukushima, Japan
      • Research Site
  • Hokkaido
    • Asahikawa, Hokkaido, Japan
      • Research Site
    • Sapporo, Hokkaido, Japan
      • Research Site
  • Hyogo
    • Himeji, Hyogo, Japan
      • Research Site
  • Kanagawa
    • Kawasaki, Kanagawa, Japan
      • Research Site
    • Yokohama, Kanagawa, Japan
      • Research Site
  • Kyoto
    • Ukyo-ku, Kyoto, Kyoto, Japan
      • Research Site
  • Nagano
    • Matsumoto, Nagano, Japan
      • Research Site
  • Oita
    • Saeki, Oita, Japan
      • Research Site
  • Osaka
    • Kishiwada, Osaka, Japan
      • Research Site
    • Kita-ku, Sakai, Osaka, Japan
      • Research Site
  • Shimane
    • Matsue, Shimane, Japan
      • Research Site
  • Tokyo
    • Chuo, Tokyo, Japan
      • Research Site
    • Nakano-ku, Tokyo, Japan
      • Research Site
  • Wakayama
    • Tanabe, Wakayama, Japan
      • Research Site
• Korea, Republic of
  • Anyang, Korea, Republic of
    • Research Site
  • Bucheon, Korea, Republic of
    • Research Site
  • Daegu, Korea, Republic of
    • Research Site
  • Seoul, Korea, Republic of
    • Research Site
  • Gyeonggi-do
    • Uijeongbu, Gyeonggi-do, Korea, Republic of
      • Research Site
  • Kangwon-do
    • Wonju, Kangwon-do, Korea, Republic of
      • Research Site
• Philippines
  • Iloilo City, Philippines
    • Research Site
  • Lipa City, Batangas, Philippines
    • Research Site
  • Quezon City, Philippines
    • Research Site
• Poland
  • Bydgoszcz, Poland
    • Research Site
  • Checiny, Poland
    • Research Site
  • Krakow, Poland
    • Research Site
  • Ostrow Wielkopolski, Poland
    • Research Site
  • Poznan, Poland
    • Research Site
  • Proszowice, Poland
    • Research Site
  • Tczew, Poland
    • Research Site
  • Wroclaw, Poland
    • Research Site
  • Zawadzkie, Poland
    • Research Site
• Russian Federation
  • Russia
    • Barnaul, Russia, Russian Federation
      • Research Site
    • Ekaterinburg, Russia, Russian Federation
      • Research Site
    • Kazan, Russia, Russian Federation
      • Research Site
    • Moscow, Russia, Russian Federation
      • Research Site
    • Novosibirsk, Russia, Russian Federation
      • Research Site
    • St.petersburg, Russia, Russian Federation
      • Research Site
• Slovakia
  • Bardejov, Slovakia
    • Research Site
  • Bojnice, Slovakia
    • Research Site
  • Bratislava, Slovakia
    • Research Site
  • Kosice, Slovakia
    • Research Site
  • Nove Mesto Nad Vahom, Slovakia
    • Research Site
  • Nove Zamky, Slovakia
    • Research Site
  • Poprad, Slovakia
    • Research Site
  • Presov, Slovakia
    • Research Site
  • Trnava, Slovakia
    • Research Site
  • Zilina, Slovakia
    • Research Site
  • Zvolen, Slovakia
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan
    • Research Site
  • Keelung, Taiwan
    • Research Site
  • Taichung, Taiwan
    • Research Site
  • Taipei, Taiwan
    • Research Site
  • Tao-yuan, Taiwan
    • Research Site
• Ukraine
  • Dnipropetrovsk, Ukraine
    • Research Site
  • Ivano-frankivsk, Ukraine
    • Research Site
  • Kharkiv, Ukraine
    • Research Site
  • Kyiv, Ukraine
    • Research Site
  • Lugansk, Ukraine
    • Research Site
• United States
  • California
    • Fullerton, California, United States
      • Research Site
  • Indiana
    • Valparaiso, Indiana, United States
      • Research Site
  • Iowa
    • Council Bluffs, Iowa, United States
      • Research Site
  • North Carolina
    • Hickory, North Carolina, United States
      • Research Site
  • Pennsylvania
    • Jefferson Hills, Pennsylvania, United States
      • Research Site
  • South Carolina
    • Gaffney, South Carolina, United States
      • Research Site
    • Greenville, South Carolina, United States
      • Research Site
    • Spartanburg, South Carolina, United States
      • Research Site
  • Texas
    • Boerne, Texas, United States
      • 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
• Smokers or ex-smokers
• Males or post-menopausal females between 40 and 80 years old
• Able to use electronic devices

Exclusion Criteria:

• Past history or current evidence of clinically significant heart disease
• Current diagnosis of asthma
• Patients who require long term oxygen therapy
• Treatment with antibiotics within 4 weeks of study visit 1b

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; AZD9668 active treatment	Drug: AZD9668; 2 x 30 mg oral tablets twice daily (bid) for 12 weeks; Drug: AZD9668; 2 x 10 mg oral tablets twice daily (bid) for 12 weeks; Drug: AZD9668; 2 x 2.5 mg oral tablets twice daily (bid) for 12 weeks
Active Comparator: 2; AZD9668 active treatment	Drug: AZD9668; 2 x 30 mg oral tablets twice daily (bid) for 12 weeks; Drug: AZD9668; 2 x 10 mg oral tablets twice daily (bid) for 12 weeks; Drug: AZD9668; 2 x 2.5 mg oral tablets twice daily (bid) for 12 weeks
Active Comparator: 3; AZD9668 active treatment	Drug: AZD9668; 2 x 30 mg oral tablets twice daily (bid) for 12 weeks; Drug: AZD9668; 2 x 10 mg oral tablets twice daily (bid) for 12 weeks; Drug: AZD9668; 2 x 2.5 mg oral tablets twice daily (bid) for 12 weeks
Placebo Comparator: 4; AZD9668 placebo treatment	Drug: AZD9668 Placebo; 2 x Matched placebo to oral tablet twice daily (bid) 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 (L) 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)	Measured at clinic visits: 1, 4, 8 and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 - End-value Measured by Patient at Home (L) in the Morning	Forced Expiratory Volume in 1 second (L)	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
Use of Reliever Medication	Daily average of number of inhalations of reliever medication	Last 6 weeks on treatment
Post-bronchodilator FEV1 (L) - Baseline	Forced Expiratory Volume in 1 second (L) 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)	Measured at clinic visits: 1, 4, 8 and 12 weeks
Pre-bronchodilator FVC (L) - Baseline	Forced Vital Capacity (L) 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)	Measured at clinic visits: 1, 4, 8 and 12 weeks
Post-bronchodilator FVC (L) - Baseline	Forced Vital Capacity (L) 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)	Measured at clinic visits: 1, 4, 8 and 12 weeks
Pre-bronchodilator IC (L) - Baseline	Inspiratory Capacity (L) 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)	Measured at clinic visits: 1, 4, 8 and 12 weeks
Post-bronchodilator IC (L) - Baseline	Inspiratory Capacity (L) 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)	Measured at clinic visits: 1, 4, 8 and 12 weeks
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 (L/min)	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
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.	Measured daily in the evening for 12 weeks
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	Measured daily in the evening for 12 weeks
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	Measured at clinic visits:1, 4, 8 and 12 weeks
Six-minute Walk Test - Distance Walked at Baseline (m)		Day 1
Six-minute Walk Test - End-value Distance Walked (m)	distance walked on vist 6 - last on treatment clinic visit	Measured Day 1 and 12 weeks
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: Claus Volgemeier, Dr., Director der Klinik fur Innere Medizin mit Schwerpunkt Pneumologie-Universitatsklinikum GieBen und Marburg, D-35043 Marburg, Germany

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.
• Vogelmeier C, Aquino TO, O'Brien CD, Perrett J, Gunawardena KA. A randomised, placebo-controlled, dose-finding study of AZD9668, an oral inhibitor of neutrophil elastase, in patients with chronic obstructive pulmonary disease treated with tiotropium. COPD. 2012 Apr;9(2):111-20. doi: 10.3109/15412555.2011.641803.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: July 21, 2009
• First Submitted That Met QC Criteria: July 30, 2009
• First Posted (Estimate): July 31, 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: COPD; Efficacy; Pharmacokinetics; Placebo-controlled; Lung; Pulmonary; Chronic; Respiratory disease; Safety and tolerability; Obstructive
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D0520C00012