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Efficacy of AZD3199 in Chronic Obstructive Pulmonary Disease (COPD) Patients (GLAD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00929708
Recruitment Status : Completed
First Posted : June 29, 2009
Results First Posted : January 17, 2014
Last Update Posted : February 17, 2014
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition COPD
Interventions Drug: AZD3199
Drug: formoterol
Drug: Placebo
Enrollment 329

Recruitment Details The study has been performed at 53 centres in Bulgaria, Canada, Japan, Poland and Russian Federation. The recruitment period was between 16 June 2009 and 8 January 2010.
Pre-assignment Details  
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening) 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening) 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening) 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening) 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Period Title: Overall Study
Started 65 69 65 67 63
Completed 61 66 62 61 57
Not Completed 4 3 3 6 6
Reason Not Completed
Protocol Violation             2             1             1             1             1
Withdrawal by Subject             2             0             0             2             1
Adverse Event             0             0             0             0             3
Physician Decision             0             2             2             2             1
Lost to Follow-up             0             0             0             1             0
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo Total
Hide Arm/Group Description 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening) 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening) 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening) 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening) 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening) Total of all reporting groups
Overall Number of Baseline Participants 65 69 65 67 63 329
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 65 participants 69 participants 65 participants 67 participants 63 participants 329 participants
62.4
(45 to 81)
63.8
(40 to 82)
65.3
(41 to 92)
64.1
(47 to 77)
64.8
(46 to 84)
63.85
(62.4 to 65.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 69 participants 65 participants 67 participants 63 participants 329 participants
Female
18
  27.7%
16
  23.2%
20
  30.8%
16
  23.9%
12
  19.0%
82
  24.9%
Male
47
  72.3%
53
  76.8%
45
  69.2%
51
  76.1%
51
  81.0%
247
  75.1%
1.Primary Outcome
Title FEV1, E0−4; the Average Value at Visit 5 From Before to 4 Hours After Morning Dose (Peak Effect)
Hide Description change from baseline
Time Frame 0,5 min, 15 min, 60 min, 2 h, 4 h
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description:
2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)
2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Number of Participants Analyzed 61 66 63 62 57
Mean (Standard Deviation)
Unit of Measure: Litre
0.21  (0.33) 0.17  (0.31) 0.14  (0.27) 0.16  (0.22) 0.03  (0.25)
2.Primary Outcome
Title FEV1, E24−26; the Average Value at Visit 5 Between 24 and 26 Hours Following the Morning Dose (Trough Effect)
Hide Description change from baseline
Time Frame 24h, 26h
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description:
2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)
2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Number of Participants Analyzed 61 66 62 62 57
Mean (Standard Deviation)
Unit of Measure: Litre
0.11  (0.31) 0.12  (0.28) 0.11  (0.25) 0.03  (0.23) 0.01  (0.24)
3.Secondary Outcome
Title Cmax; the Highest Plasma Concentration of AZD3199 Measured
Hide Description PK is only measured for AZD3199
Time Frame 0,15 min, 1, 4 and 24 hours post dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
AZD3199 plasma data were available for 178 of the 199 randomized patients, but data from 2 patients in AZD3199 200 mcg group were excluded from analysis because most of the values were below LOQ.
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description:
2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)
2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Number of Participants Analyzed 53 64 59 0 0
Geometric Mean (Full Range)
Unit of Measure: nmol/L
1.14
(0.03 to 3.6)
1.88
(0.05 to 9.8)
4.01
(0.12 to 18.2)
4.Secondary Outcome
Title AUC0-24; Area Under the Plasma Concentration Curve From Zero to 24 Hours After Dose
Hide Description PK is only measured for AZD3199
Time Frame 0,15 min, 1, 4 and 24 hours post dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
AZD3199 plasma data were available for 178 of the 199 randomized patients, but data from 2 patients in AZD3199 200 mcg group were excluded from analysis because most of the values were below LOQ.
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description:
2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)
2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Number of Participants Analyzed 53 64 59 0 0
Geometric Mean (Full Range)
Unit of Measure: nmol*h/L
4.83
(0.4 to 20.8)
8.69
(0.7 to 54.1)
14.82
(1.4 to 76.3)
5.Secondary Outcome
Title FEV1 Post Salbutamol Inhalation
Hide Description Mean value of FEV1 pre and post salbutamol at visit 2 and visit 5
Time Frame Baseline (visit 2) and 26 h after the last morning dose (visit 5).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description:
2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)
2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Number of Participants Analyzed 61 62 61 61 54
Mean (Standard Deviation)
Unit of Measure: Litre
0.060  (0.306) 0.073  (0.358) 0.077  (0.238) 0.048  (0.260) 0.018  (0.215)
6.Secondary Outcome
Title Total Number of Reliever Medication Inhalations Per 24h
Hide Description Change from run-in
Time Frame During day (from rising from bed until going to bed) and night (from going to bed until rising from bed) at visit 1 to visit 5 (24h), up to 4 weeks.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description:
2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)
2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Number of Participants Analyzed 64 66 64 63 60
Mean (Standard Deviation)
Unit of Measure: Number of reliver inh.
-0.96  (1.85) -1.23  (1.96) -1.15  (1.55) -0.66  (1.40) -0.23  (1.58)
7.Secondary Outcome
Title Total AstraZeneca COPD Symptoms Scores (Included Breathlessness, Chest Tightness, Cough and Night-time Awakenings)
Hide Description Score on a scale 5-point Likert-type scale, ranging from 0 (none) to 4 (severe) for each symptom, total score is the sum of each symptom ranged from 0 to 16. Change from run-in.
Time Frame Daily, during run-in and treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description:
2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)
2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Number of Participants Analyzed 64 66 64 63 60
Mean (Standard Deviation)
Unit of Measure: total score
-0.96  (1.34) -0.91  (1.65) -1.21  (1.53) -0.56  (1.83) -0.43  (1.61)
8.Secondary Outcome
Title Overall Mean CCQ (Clinical COPD Questionnaire)
Hide Description Change from baseline to treatment in score. The total scores vary between 0 (never/not limited at all) to 6 (almost all the time/totally limited). The data below represent the average of week 1,2,4 minus week 0.
Time Frame Mean over week 0, mean over week 1, mean over week 2, and mean over week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description:
2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)
2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Number of Participants Analyzed 64 69 64 66 61
Mean (Standard Deviation)
Unit of Measure: score on scale
-0.39  (0.49) -0.29  (0.65) -0.39  (0.54) -0.35  (0.65) -0.10  (0.70)
9.Secondary Outcome
Title Total Score SGRQ-C (St George’s Respiratory Questionnaire for COPD)
Hide Description The total score is calculated using all questions including their weights and scores range from 0 (perfect health) to 100 (worst possible state)
Time Frame At baseline (visit 2) and after 4 weeks of treatment (visit 5).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description:
2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)
2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)
2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Number of Participants Analyzed 59 66 61 58 53
Mean (Standard Deviation)
Unit of Measure: Score
-5.10  (13.67) -8.17  (12.18) -5.01  (10.69) -5.16  (10.88) -2.35  (12.98)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Hide Arm/Group Description 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening) 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening) 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening) 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening) 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
All-Cause Mortality
AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/65 (1.54%)   4/69 (5.80%)   0/65 (0.00%)   3/67 (4.48%)   2/63 (3.17%) 
Eye disorders           
Macular degeneration *  0/65 (0.00%)  0/69 (0.00%)  0/65 (0.00%)  1/67 (1.49%)  0/63 (0.00%) 
Gastrointestinal disorders           
Colitis ishaemic *  0/65 (0.00%)  0/69 (0.00%)  0/65 (0.00%)  1/67 (1.49%)  0/63 (0.00%) 
Infections and infestations           
Pneumonia bacterial *  0/65 (0.00%)  0/69 (0.00%)  0/65 (0.00%)  1/67 (1.49%)  0/63 (0.00%) 
Injury, poisoning and procedural complications           
Clavicle fracture *  0/65 (0.00%)  1/69 (1.45%)  0/65 (0.00%)  0/67 (0.00%)  0/63 (0.00%) 
Head injury *  0/65 (0.00%)  1/69 (1.45%)  0/65 (0.00%)  0/67 (0.00%)  0/63 (0.00%) 
Rib fracture *  0/65 (0.00%)  1/69 (1.45%)  0/65 (0.00%)  0/67 (0.00%)  0/63 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Chroniv obstructive pulmonary disease *  1/65 (1.54%)  0/69 (0.00%)  0/65 (0.00%)  0/67 (0.00%)  0/63 (0.00%) 
Pleural effusion *  0/65 (0.00%)  1/69 (1.45%)  0/65 (0.00%)  0/67 (0.00%)  0/63 (0.00%) 
Vascular disorders           
Hypertensive crisis *  0/65 (0.00%)  0/69 (0.00%)  0/65 (0.00%)  0/67 (0.00%)  1/63 (1.59%) 
Circulatory collapse *  0/65 (0.00%)  0/69 (0.00%)  0/65 (0.00%)  0/67 (0.00%)  1/63 (1.59%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZD3199 200 Mcg od AZD3199 400 Mcg od AZD3199 800 Mcg od Formoterol 9 Mcg Bid Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/65 (1.54%)   8/69 (11.59%)   7/65 (10.77%)   4/67 (5.97%)   3/63 (4.76%) 
Infections and infestations           
Nasopharyngitis *  1/65 (1.54%)  4/69 (5.80%)  3/65 (4.62%)  2/67 (2.99%)  3/63 (4.76%) 
Respiratory, thoracic and mediastinal disorders           
Cough *  0/65 (0.00%)  4/69 (5.80%)  4/65 (6.15%)  2/67 (2.99%)  0/63 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
An Investigator agrees to provide a copy of the publication to AZ for review at least 60 days in advance of submission for publication. Investigators in multicenter (MC) studies agree to postpone MC publications until the earlier of the date of the first AZ-authorized MC publication or a period up to 18 months from study completion at all sites. AZ has the right to request delays: up to 60 days for confidential information, and an additional 90 days to protect intellectual property.
Results Point of Contact
Name/Title: Carin Jorup, MSD
Organization: AstraZeneca
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00929708     History of Changes
Other Study ID Numbers: D0570C00003
First Submitted: June 26, 2009
First Posted: June 29, 2009
Results First Submitted: December 20, 2012
Results First Posted: January 17, 2014
Last Update Posted: February 17, 2014