Trial Outcomes & Findings for Efficacy and Safety Study of Two Fixed-dose Combinations of Aclidinium Bromide With Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo (NCT NCT01049360)
NCT ID: NCT01049360
Last Updated: 2017-02-28
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
128 participants
Primary outcome timeframe
0 to 12 hours post-dose on Day 14
Results posted on
2017-02-28
Participant Flow
The study was conducted in a total of 20 study centers in the United States. The first patient was screened in December 2009 and the last patient visit was in August 2010.
Participant milestones
| Measure |
Sequence 1
Aclidiunium/Formoterol 400/6 - Aclidiunium/Formoterol 400/12 - Aclidinium - Formoterol
|
Sequence 2
Aclidinium/Formoterol 400/12 - Aclidinium - Formoterol - Placebo
|
Sequence 3
Aclidinium - Formoterol - Placebo - Aclidinium/Formoterol 400/6
|
Sequence 4
Formoterol - Placebo - Aclidinium/Formoterol 400/6 - Aclidinium/Formoterol 400/12
|
Sequence 5
Placebo - Aclidinium/Formoterol 400/6 - Aclidinium/Formoterol 400/12 - Aclidinium
|
Sequence 6
Aclidinium/Formoterol 400/6 - Aclidinium - Placebo - Aclidinium/Formoterol 400/12
|
Sequence 7
Aclidinium/Formoterol 400/12 - Formoterol - Aclidinium/Formoterol 400/6 - Aclidinium
|
Sequence 8
Aclidinium - Placebo - Aclidinium/Formoterol 400/12 - Formoterol
|
Sequence 9
Formoterol - Aclidinium/Formoterol 400/6 - Aclidinium - Placebo
|
Sequence 10
Placebo - Aclidinium/Formoterol 400/12 - Formoterol - Aclidinium/Formoterol 400/6
|
Sequence 11
Aclidinium/Formoterol 400/6 - Formoterol - Aclidinium/Formoterol 400/12 - Placebo
|
Sequence 12
Aclidinium/Formoterol 400/12 - Placebo - Aclidinium - Aclidinium/Formoterol 400/6
|
Sequence 13
Aclidinium - Aclidinium/Formoterol 400/6 - Formoterol - Aclidinium/Formoterol 400/12
|
Sequence 14
Formoterol - Aclidinium/Formoterol 400/12 - Placebo - Aclidinium
|
Sequence 15
Placebo - Aclidinium - Aclidinium/Formoterol 400/6 - Formoterol
|
Sequence 16
Aclidinium/Formoterol 400/6 - Placebo - Formoterol - Aclidinium
|
Sequence 17
Aclidinium/Formoterol 400/12 - Aclidinium/Formoterol 400/6 - Placebo - Formoterol
|
Sequence 18
Aclidinium - Aclidinium/Formoterol 400/12 - Aclidinium/Formoterol 400/6 - Placebo
|
Sequence 19
Formoterol - Aclidinium - Aclidinium/Formoterol 400/12 - Aclidinium/Formoterol 400/6
|
Sequence 20
Placebo - Formoterol - Aclidinium - Aclidinium/Formoterol 400/12
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
6
|
6
|
7
|
7
|
7
|
6
|
6
|
6
|
7
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6
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6
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6
|
6
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7
|
7
|
7
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6
|
6
|
6
|
7
|
|
Period 1
COMPLETED
|
6
|
5
|
7
|
6
|
7
|
6
|
6
|
4
|
5
|
6
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5
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6
|
4
|
6
|
7
|
7
|
5
|
6
|
5
|
7
|
|
Period 1
NOT COMPLETED
|
0
|
1
|
0
|
1
|
0
|
0
|
0
|
2
|
2
|
0
|
1
|
0
|
2
|
1
|
0
|
0
|
1
|
0
|
1
|
0
|
|
Period 2
STARTED
|
6
|
5
|
7
|
6
|
7
|
6
|
6
|
4
|
5
|
6
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5
|
6
|
4
|
6
|
7
|
7
|
5
|
6
|
5
|
7
|
|
Period 2
COMPLETED
|
6
|
4
|
7
|
4
|
7
|
5
|
6
|
4
|
4
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6
|
5
|
6
|
4
|
6
|
5
|
6
|
5
|
6
|
5
|
5
|
|
Period 2
NOT COMPLETED
|
0
|
1
|
0
|
2
|
0
|
1
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
2
|
1
|
0
|
0
|
0
|
2
|
|
Period 3
STARTED
|
6
|
4
|
7
|
4
|
7
|
5
|
6
|
4
|
4
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6
|
5
|
6
|
4
|
6
|
5
|
6
|
5
|
6
|
5
|
5
|
|
Period 3
COMPLETED
|
6
|
4
|
7
|
4
|
7
|
5
|
6
|
4
|
4
|
6
|
5
|
6
|
4
|
6
|
5
|
6
|
5
|
6
|
5
|
5
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
6
|
4
|
7
|
4
|
7
|
5
|
6
|
4
|
4
|
6
|
5
|
6
|
4
|
6
|
5
|
6
|
5
|
6
|
5
|
5
|
|
Period 4
COMPLETED
|
6
|
4
|
7
|
3
|
7
|
5
|
6
|
4
|
4
|
6
|
5
|
6
|
4
|
6
|
5
|
6
|
5
|
5
|
5
|
5
|
|
Period 4
NOT COMPLETED
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1
Aclidiunium/Formoterol 400/6 - Aclidiunium/Formoterol 400/12 - Aclidinium - Formoterol
|
Sequence 2
Aclidinium/Formoterol 400/12 - Aclidinium - Formoterol - Placebo
|
Sequence 3
Aclidinium - Formoterol - Placebo - Aclidinium/Formoterol 400/6
|
Sequence 4
Formoterol - Placebo - Aclidinium/Formoterol 400/6 - Aclidinium/Formoterol 400/12
|
Sequence 5
Placebo - Aclidinium/Formoterol 400/6 - Aclidinium/Formoterol 400/12 - Aclidinium
|
Sequence 6
Aclidinium/Formoterol 400/6 - Aclidinium - Placebo - Aclidinium/Formoterol 400/12
|
Sequence 7
Aclidinium/Formoterol 400/12 - Formoterol - Aclidinium/Formoterol 400/6 - Aclidinium
|
Sequence 8
Aclidinium - Placebo - Aclidinium/Formoterol 400/12 - Formoterol
|
Sequence 9
Formoterol - Aclidinium/Formoterol 400/6 - Aclidinium - Placebo
|
Sequence 10
Placebo - Aclidinium/Formoterol 400/12 - Formoterol - Aclidinium/Formoterol 400/6
|
Sequence 11
Aclidinium/Formoterol 400/6 - Formoterol - Aclidinium/Formoterol 400/12 - Placebo
|
Sequence 12
Aclidinium/Formoterol 400/12 - Placebo - Aclidinium - Aclidinium/Formoterol 400/6
|
Sequence 13
Aclidinium - Aclidinium/Formoterol 400/6 - Formoterol - Aclidinium/Formoterol 400/12
|
Sequence 14
Formoterol - Aclidinium/Formoterol 400/12 - Placebo - Aclidinium
|
Sequence 15
Placebo - Aclidinium - Aclidinium/Formoterol 400/6 - Formoterol
|
Sequence 16
Aclidinium/Formoterol 400/6 - Placebo - Formoterol - Aclidinium
|
Sequence 17
Aclidinium/Formoterol 400/12 - Aclidinium/Formoterol 400/6 - Placebo - Formoterol
|
Sequence 18
Aclidinium - Aclidinium/Formoterol 400/12 - Aclidinium/Formoterol 400/6 - Placebo
|
Sequence 19
Formoterol - Aclidinium - Aclidinium/Formoterol 400/12 - Aclidinium/Formoterol 400/6
|
Sequence 20
Placebo - Formoterol - Aclidinium - Aclidinium/Formoterol 400/12
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Period 1
Adverse Event
|
0
|
1
|
0
|
1
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
1
|
1
|
0
|
0
|
1
|
0
|
1
|
0
|
|
Period 1
Did not meet inc/exc criteria
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 1
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
1
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
Protocol Violation
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Period 2
Adverse Event
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Period 2
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
1
|
|
Period 2
Lack of Efficacy
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 4
Protocol Violation
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Period 4
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Efficacy and Safety Study of Two Fixed-dose Combinations of Aclidinium Bromide With Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo
Baseline characteristics by cohort
| Measure |
Overall Population
n=128 Participants
Safety population defined as all randomized patients who took at least one dose of double-blind investigational product
|
|---|---|
|
Age, Continuous
|
61.5 Years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Gender
Female
|
73 Participants
n=5 Participants
|
|
Gender
Male
|
55 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0 to 12 hours post-dose on Day 14Population: ITT Population defined as randomized patients who took at least one dose of double-blind investigational product and who had at least 1 baseline and 1 post-baseline assessment of FEV1
Outcome measures
| Measure |
Aclidinium 400 μg / Formoterol 12 μg
n=78 Participants
Aclidinium bromide 400 μg / formoterol fumarate 12 μg fixed dose combination administered twice-daily (BID)
|
Aclidinium 400 μg / Formoterol 6 μg
n=83 Participants
Aclidinium bromide 400 μg / formoterol fumarate 6 μg fixed dose combination administered twice-daily (BID)
|
Aclidinium 400 μg
n=82 Participants
Aclidinium bromide 400 μg administered twice-daily (BID)
|
Formoterol 12 μg
n=75 Participants
Formoterol fumarate 12 μg twice-daily
|
Placebo
n=81 Participants
Placebo twice-daily
|
|---|---|---|---|---|---|
|
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12)
|
0.187 Liters
Standard Error 0.019
|
0.189 Liters
Standard Error 0.018
|
0.144 Liters
Standard Error 0.018
|
0.114 Liters
Standard Error 0.019
|
-0.013 Liters
Standard Error 0.018
|
SECONDARY outcome
Timeframe: Day 14Population: ITT Population defined as randomized patients who took at least one dose of double-blind investigational product and who had at least 1 baseline and 1 post-baseline assessment of FEV1
Outcome measures
| Measure |
Aclidinium 400 μg / Formoterol 12 μg
n=84 Participants
Aclidinium bromide 400 μg / formoterol fumarate 12 μg fixed dose combination administered twice-daily (BID)
|
Aclidinium 400 μg / Formoterol 6 μg
n=90 Participants
Aclidinium bromide 400 μg / formoterol fumarate 6 μg fixed dose combination administered twice-daily (BID)
|
Aclidinium 400 μg
n=90 Participants
Aclidinium bromide 400 μg administered twice-daily (BID)
|
Formoterol 12 μg
n=85 Participants
Formoterol fumarate 12 μg twice-daily
|
Placebo
n=88 Participants
Placebo twice-daily
|
|---|---|---|---|---|---|
|
Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1)
|
0.124 Liters
Standard Error 0.018
|
0.129 Liters
Standard Error 0.018
|
0.080 Liters
Standard Error 0.018
|
0.071 Liters
Standard Error 0.018
|
-0.008 Liters
Standard Error 0.018
|
SECONDARY outcome
Timeframe: Day 14Population: ITT Population defined as randomized patients who took at least one dose of double-blind investigational product and who had at least 1 baseline and 1 post-baseline assessment of FEV1
Outcome measures
| Measure |
Aclidinium 400 μg / Formoterol 12 μg
n=84 Participants
Aclidinium bromide 400 μg / formoterol fumarate 12 μg fixed dose combination administered twice-daily (BID)
|
Aclidinium 400 μg / Formoterol 6 μg
n=90 Participants
Aclidinium bromide 400 μg / formoterol fumarate 6 μg fixed dose combination administered twice-daily (BID)
|
Aclidinium 400 μg
n=90 Participants
Aclidinium bromide 400 μg administered twice-daily (BID)
|
Formoterol 12 μg
n=85 Participants
Formoterol fumarate 12 μg twice-daily
|
Placebo
n=87 Participants
Placebo twice-daily
|
|---|---|---|---|---|---|
|
Change From Baseline in Morning Peak Forced Expiratory Volume in One Second (FEV1)
|
0.355 Liters
Standard Error 0.022
|
0.348 Liters
Standard Error 0.021
|
0.260 Liters
Standard Error 0.021
|
0.245 Liters
Standard Error 0.022
|
0.073 Liters
Standard Error 0.022
|
Adverse Events
Aclidinium 400 μg / Formoterol 12 μg
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Aclidinium 400 μg / Formoterol 6 μg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Aclidinium 400 μg
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Formoterol 12 μg
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Aclidinium 400 μg / Formoterol 12 μg
n=87 participants at risk
Aclidinium bromide 400 μg / formoterol fumarate 12 μg fixed dose combination administered twice-daily (BID)
|
Aclidinium 400 μg / Formoterol 6 μg
n=91 participants at risk
Aclidinium bromide 400 μg / formoterol fumarate 6 μg fixed dose combination administered twice-daily (BID)
|
Aclidinium 400 μg
n=94 participants at risk
Aclidinium bromide 400 μg administered twice-daily (BID)
|
Formoterol 12 μg
n=92 participants at risk
Formoterol fumarate 12 μg twice-daily
|
Placebo
n=92 participants at risk
Placebo twice-daily
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.3%
2/87 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/91 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/94 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/92 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/92 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.1%
1/87 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/91 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/94 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/92 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/92 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
|
Renal and urinary disorders
Renal failure acute
|
1.1%
1/87 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/91 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/94 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/92 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/92 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic renal cell carcinoma
|
0.00%
0/87 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/91 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
1.1%
1/94 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/92 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/92 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
|
Cardiac disorders
Coronary artery occlusion
|
0.00%
0/87 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/91 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/94 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
1.1%
1/92 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
0.00%
0/92 • Up to 30 days after the last dose of investigational product, for up to 24 weeks
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Publication of the results by the Investigator will be subject to mutual agreement between the investigator and sponsor.
- Publication restrictions are in place
Restriction type: OTHER