Trial Outcomes & Findings for Efficacy of AZD3199 in Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT NCT00929708)

Results Overview

change from baseline

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

329 participants

Primary outcome timeframe

0,5 min, 15 min, 60 min, 2 h, 4 h

Results posted on

2014-02-17

Participant Flow

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.

Participant milestones

Participant milestones
Measure	AZD3199 200 Mcg od 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Study STARTED	65	69	65	67	63
Overall Study COMPLETED	61	66	62	61	57
Overall Study NOT COMPLETED	4	3	3	6	6

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD3199 200 Mcg od 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Study Protocol Violation	2	1	1	1	1
Overall Study Withdrawal by Subject	2	0	0	2	1
Overall Study Adverse Event	0	0	0	0	3
Overall Study Physician Decision	0	2	2	2	1
Overall Study Lost to Follow-up	0	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD3199 200 Mcg od n=65 Participants 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=69 Participants 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=65 Participants 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid n=67 Participants 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo n=63 Participants 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)	Total n=329 Participants Total of all reporting groups
Age, Continuous	62.4 Years n=5 Participants	63.8 Years n=7 Participants	65.3 Years n=5 Participants	64.1 Years n=4 Participants	64.8 Years n=21 Participants	63.85 Years n=10 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants	16 Participants n=4 Participants	12 Participants n=21 Participants	82 Participants n=10 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	53 Participants n=7 Participants	45 Participants n=5 Participants	51 Participants n=4 Participants	51 Participants n=21 Participants	247 Participants n=10 Participants

PRIMARY outcome

Timeframe: 0,5 min, 15 min, 60 min, 2 h, 4 h

change from baseline

Outcome measures

Outcome measures
Measure	AZD3199 200 Mcg od n=61 Participants 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=66 Participants 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=63 Participants 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid n=62 Participants 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo n=57 Participants 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
FEV1, E0-4; the Average Value at Visit 5 From Before to 4 Hours After Morning Dose (Peak Effect)	0.21 Litre Standard Deviation 0.33	0.17 Litre Standard Deviation 0.31	0.14 Litre Standard Deviation 0.27	0.16 Litre Standard Deviation 0.22	0.03 Litre Standard Deviation 0.25

PRIMARY outcome

Timeframe: 24h, 26h

change from baseline

Outcome measures

Outcome measures
Measure	AZD3199 200 Mcg od n=61 Participants 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=66 Participants 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=62 Participants 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid n=62 Participants 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo n=57 Participants 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
FEV1, E24-26; the Average Value at Visit 5 Between 24 and 26 Hours Following the Morning Dose (Trough Effect)	0.11 Litre Standard Deviation 0.31	0.12 Litre Standard Deviation 0.28	0.11 Litre Standard Deviation 0.25	0.03 Litre Standard Deviation 0.23	0.01 Litre Standard Deviation 0.24

SECONDARY outcome

Timeframe: 0,15 min, 1, 4 and 24 hours post dose

Population: 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.

PK is only measured for AZD3199

Outcome measures

Outcome measures
Measure	AZD3199 200 Mcg od n=53 Participants 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=64 Participants 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=59 Participants 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Cmax; the Highest Plasma Concentration of AZD3199 Measured	1.14 nmol/L Interval 0.03 to 3.6	1.88 nmol/L Interval 0.05 to 9.8	4.01 nmol/L Interval 0.12 to 18.2	—	—

SECONDARY outcome

Timeframe: 0,15 min, 1, 4 and 24 hours post dose

Population: 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.

PK is only measured for AZD3199

Outcome measures

Outcome measures
Measure	AZD3199 200 Mcg od n=53 Participants 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=64 Participants 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=59 Participants 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
AUC0-24; Area Under the Plasma Concentration Curve From Zero to 24 Hours After Dose	4.83 nmol*h/L Interval 0.4 to 20.8	8.69 nmol*h/L Interval 0.7 to 54.1	14.82 nmol*h/L Interval 1.4 to 76.3	—	—

SECONDARY outcome

Timeframe: Baseline (visit 2) and 26 h after the last morning dose (visit 5).

Mean value of FEV1 pre and post salbutamol at visit 2 and visit 5

Outcome measures

Outcome measures
Measure	AZD3199 200 Mcg od n=61 Participants 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=62 Participants 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=61 Participants 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid n=61 Participants 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo n=54 Participants 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
FEV1 Post Salbutamol Inhalation	0.060 Litre Standard Deviation 0.306	0.073 Litre Standard Deviation 0.358	0.077 Litre Standard Deviation 0.238	0.048 Litre Standard Deviation 0.260	0.018 Litre Standard Deviation 0.215

SECONDARY outcome

Timeframe: 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.

Change from run-in

Outcome measures

Outcome measures
Measure	AZD3199 200 Mcg od n=64 Participants 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=66 Participants 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=64 Participants 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid n=63 Participants 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo n=60 Participants 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Total Number of Reliever Medication Inhalations Per 24h	-0.96 Number of reliver inh. Standard Deviation 1.85	-1.23 Number of reliver inh. Standard Deviation 1.96	-1.15 Number of reliver inh. Standard Deviation 1.55	-0.66 Number of reliver inh. Standard Deviation 1.40	-0.23 Number of reliver inh. Standard Deviation 1.58

SECONDARY outcome

Timeframe: Daily, during run-in and treatment

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.

Outcome measures

Outcome measures
Measure	AZD3199 200 Mcg od n=64 Participants 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=66 Participants 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=64 Participants 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid n=63 Participants 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo n=60 Participants 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Total AstraZeneca COPD Symptoms Scores (Included Breathlessness, Chest Tightness, Cough and Night-time Awakenings)	-0.96 total score Standard Deviation 1.34	-0.91 total score Standard Deviation 1.65	-1.21 total score Standard Deviation 1.53	-0.56 total score Standard Deviation 1.83	-0.43 total score Standard Deviation 1.61

SECONDARY outcome

Timeframe: Mean over week 0, mean over week 1, mean over week 2, and mean over week 4

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.

Outcome measures

Outcome measures
Measure	AZD3199 200 Mcg od n=64 Participants 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=69 Participants 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=64 Participants 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid n=66 Participants 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo n=61 Participants 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Overall Mean CCQ (Clinical COPD Questionnaire)	-0.39 score on scale Standard Deviation 0.49	-0.29 score on scale Standard Deviation 0.65	-0.39 score on scale Standard Deviation 0.54	-0.35 score on scale Standard Deviation 0.65	-0.10 score on scale Standard Deviation 0.70

SECONDARY outcome

Timeframe: At baseline (visit 2) and after 4 weeks of treatment (visit 5).

The total score is calculated using all questions including their weights and scores range from 0 (perfect health) to 100 (worst possible state)

Outcome measures

Outcome measures
Measure	AZD3199 200 Mcg od n=59 Participants 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=66 Participants 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=61 Participants 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid n=58 Participants 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo n=53 Participants 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Total Score SGRQ-C (St George's Respiratory Questionnaire for COPD)	-5.10 Score Standard Deviation 13.67	-8.17 Score Standard Deviation 12.18	-5.01 Score Standard Deviation 10.69	-5.16 Score Standard Deviation 10.88	-2.35 Score Standard Deviation 12.98

Adverse Events

AZD3199 200 Mcg od

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

AZD3199 400 Mcg od

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

AZD3199 800 Mcg od

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Formoterol 9 Mcg Bid

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AZD3199 200 Mcg od n=65 participants at risk 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=69 participants at risk 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=65 participants at risk 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid n=67 participants at risk 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo n=63 participants at risk 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Respiratory, thoracic and mediastinal disorders Chroniv obstructive pulmonary disease	1.5% 1/65	0.00% 0/69	0.00% 0/65	0.00% 0/67	0.00% 0/63
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/65	1.4% 1/69	0.00% 0/65	0.00% 0/67	0.00% 0/63
Gastrointestinal disorders Colitis ishaemic	0.00% 0/65	0.00% 0/69	0.00% 0/65	1.5% 1/67	0.00% 0/63
Injury, poisoning and procedural complications Head injury	0.00% 0/65	1.4% 1/69	0.00% 0/65	0.00% 0/67	0.00% 0/63
Vascular disorders Hypertensive crisis	0.00% 0/65	0.00% 0/69	0.00% 0/65	0.00% 0/67	1.6% 1/63
Eye disorders Macular degeneration	0.00% 0/65	0.00% 0/69	0.00% 0/65	1.5% 1/67	0.00% 0/63
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/65	1.4% 1/69	0.00% 0/65	0.00% 0/67	0.00% 0/63
Infections and infestations Pneumonia bacterial	0.00% 0/65	0.00% 0/69	0.00% 0/65	1.5% 1/67	0.00% 0/63
Injury, poisoning and procedural complications Rib fracture	0.00% 0/65	1.4% 1/69	0.00% 0/65	0.00% 0/67	0.00% 0/63
Vascular disorders Circulatory collapse	0.00% 0/65	0.00% 0/69	0.00% 0/65	0.00% 0/67	1.6% 1/63

Other adverse events

Other adverse events
Measure	AZD3199 200 Mcg od n=65 participants at risk 2 x AZD3199 Turbuhaler 100 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 400 Mcg od n=69 participants at risk 2 x AZD3199 Turbuhaler 200 mcg (morning) + 2 x placebo Turbuhaler (evening)	AZD3199 800 Mcg od n=65 participants at risk 2 x AZD3199 Turbuhaler 400 mcg (morning) + 2 x placebo Turbuhaler (evening)	Formoterol 9 Mcg Bid n=67 participants at risk 2 x Oxis Turbuhaler 4.5 mcg (morning) + 2 x Oxis Turbuhaler 4.5 mcg (evening)	Placebo n=63 participants at risk 2 x placebo Turbuhaler (morning) + 2 x placebo Turbuhaler (evening)
Infections and infestations Nasopharyngitis	1.5% 1/65	5.8% 4/69	4.6% 3/65	3.0% 2/67	4.8% 3/63
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/65	5.8% 4/69	6.2% 4/65	3.0% 2/67	0.00% 0/63

Additional Information

Carin Jorup, MSD

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
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Restriction type: OTHER