Trial Outcomes & Findings for Efficacy and Safety of Two Fixed Dose Combinations of Aclidinium Bromide With Formoterol Fumarate (NCT NCT01078623)
NCT ID: NCT01078623
Last Updated: 2017-02-23
Results Overview
FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
176 participants
Primary outcome timeframe
0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14
Results posted on
2017-02-23
Participant Flow
This study was conducted at a total of 28 sites (4 sites in Czech Republic, 5 sites in Germany, 3 sites in Hungary, 4 sites in Poland and 12 sites in Romania) The first patient was screened in February 2010 and the last patient visit was in September 2010
A total of 176 patients were screened of whom 135 were assessed as eligible and were randomized into the study There were 41 screen failures, the main reason being non-fulfilment of inclusion/exclusion criteria
Participant milestones
| Measure |
Sequence 1
FDC 200/6 μg - FDC 200/12 μg - Aclidinium 200 μg - Formoterol 12 μg
|
Sequence 2
FDC 200/12 - Aclidinium 200 - Formoterol 12 - Placebo
|
Sequence 3
Aclidinium 200 - Formoterol 12 - Placebo - FDC 200/6
|
Sequence 4
Formoterol 12 - Placebo - FDC 200/6 - FDC 200/12
|
Sequence 5
Placebo - FDC 200/6 - FDC 200/12 - Aclidinium 200
|
Sequence 6
FDC 200/6 - Aclidinium 200 - Placebo - FDC 200/12
|
Sequence 7
FDC 200/12 - Formoterol 12 - FDC 200/6 - Aclidinium 200
|
Sequence 8
Aclidinium 200 - Placebo - FDC 200/12 - Formoterol 12
|
Sequence 9
Formoterol 12 - FDC 200/6 - Aclidinium 200 - Placebo
|
Sequence 10
Placebo - FDC 200/12 - Formoterol 12 - FDC 200/6
|
Sequence 11
FDC 200/6 - Formoterol 12 - FDC 200/12 - Placebo
|
Sequence 12
FDC 200/12 - Placebo - Aclidinium 200 - FDC 200/6
|
Sequence 13
Aclidinium 200 - FDC 200/6 - Formoterol 12 - FDC 200/12
|
Sequence 14
Formoterol 12 - FDC 200/12 - Placebo - Aclidinium 200
|
Sequence 15
Placebo - Aclidinium 200 - FDC 200/6 - Formoterol 12
|
Sequence 16
FDC 200/6 - Placebo - Formoterol 12 - Aclidinium 200
|
Sequence 17
FDC 200/12 - FDC 200/6 - Placebo - Formoterol 12
|
Sequence 18
Aclidinium 200 - FDC 200/12 - FDC 200/6 - Placebo
|
Sequence 19
Formoterol 12 - Aclidinium 200 - FDC 200/12 - FDC 200/6
|
Sequence 20
Placebo - Formoterol 12 - Aclidinium 200 - FDC 200/12
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Treatment Period 1
STARTED
|
6
|
6
|
7
|
6
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7
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6
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7
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7
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6
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7
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7
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7
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7
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7
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7
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7
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7
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7
|
7
|
7
|
|
Treatment Period 1
COMPLETED
|
5
|
5
|
6
|
6
|
7
|
5
|
6
|
6
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5
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6
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6
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7
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7
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7
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7
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7
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7
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7
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7
|
7
|
|
Treatment Period 1
NOT COMPLETED
|
1
|
1
|
1
|
0
|
0
|
1
|
1
|
1
|
1
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 2
STARTED
|
5
|
5
|
6
|
6
|
7
|
5
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6
|
6
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5
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6
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6
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7
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7
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7
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7
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7
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7
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7
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7
|
7
|
|
Treatment Period 2
COMPLETED
|
5
|
5
|
6
|
6
|
7
|
4
|
5
|
6
|
5
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6
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6
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7
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7
|
7
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7
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7
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7
|
7
|
6
|
7
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Treatment Period 3
STARTED
|
5
|
5
|
6
|
6
|
7
|
4
|
5
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6
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5
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6
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6
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7
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7
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7
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7
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7
|
7
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7
|
6
|
7
|
|
Treatment Period 3
COMPLETED
|
5
|
5
|
6
|
6
|
6
|
4
|
5
|
6
|
5
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6
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6
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7
|
7
|
6
|
7
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7
|
7
|
7
|
6
|
7
|
|
Treatment Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 4
STARTED
|
5
|
5
|
6
|
6
|
6
|
4
|
5
|
6
|
5
|
6
|
6
|
7
|
7
|
6
|
7
|
7
|
7
|
7
|
6
|
7
|
|
Treatment Period 4
COMPLETED
|
5
|
5
|
5
|
6
|
6
|
4
|
5
|
6
|
5
|
6
|
6
|
7
|
7
|
6
|
7
|
6
|
7
|
7
|
6
|
7
|
|
Treatment Period 4
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1
FDC 200/6 μg - FDC 200/12 μg - Aclidinium 200 μg - Formoterol 12 μg
|
Sequence 2
FDC 200/12 - Aclidinium 200 - Formoterol 12 - Placebo
|
Sequence 3
Aclidinium 200 - Formoterol 12 - Placebo - FDC 200/6
|
Sequence 4
Formoterol 12 - Placebo - FDC 200/6 - FDC 200/12
|
Sequence 5
Placebo - FDC 200/6 - FDC 200/12 - Aclidinium 200
|
Sequence 6
FDC 200/6 - Aclidinium 200 - Placebo - FDC 200/12
|
Sequence 7
FDC 200/12 - Formoterol 12 - FDC 200/6 - Aclidinium 200
|
Sequence 8
Aclidinium 200 - Placebo - FDC 200/12 - Formoterol 12
|
Sequence 9
Formoterol 12 - FDC 200/6 - Aclidinium 200 - Placebo
|
Sequence 10
Placebo - FDC 200/12 - Formoterol 12 - FDC 200/6
|
Sequence 11
FDC 200/6 - Formoterol 12 - FDC 200/12 - Placebo
|
Sequence 12
FDC 200/12 - Placebo - Aclidinium 200 - FDC 200/6
|
Sequence 13
Aclidinium 200 - FDC 200/6 - Formoterol 12 - FDC 200/12
|
Sequence 14
Formoterol 12 - FDC 200/12 - Placebo - Aclidinium 200
|
Sequence 15
Placebo - Aclidinium 200 - FDC 200/6 - Formoterol 12
|
Sequence 16
FDC 200/6 - Placebo - Formoterol 12 - Aclidinium 200
|
Sequence 17
FDC 200/12 - FDC 200/6 - Placebo - Formoterol 12
|
Sequence 18
Aclidinium 200 - FDC 200/12 - FDC 200/6 - Placebo
|
Sequence 19
Formoterol 12 - Aclidinium 200 - FDC 200/12 - FDC 200/6
|
Sequence 20
Placebo - Formoterol 12 - Aclidinium 200 - FDC 200/12
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Treatment Period 1
Adverse Event
|
1
|
1
|
1
|
0
|
0
|
0
|
1
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 1
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 1
Protocol Violation
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 2
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Treatment Period 2
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3
Adverse Event
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 4
Adverse Event
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 4
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Efficacy and Safety of Two Fixed Dose Combinations of Aclidinium Bromide With Formoterol Fumarate
Baseline characteristics by cohort
| Measure |
Overall Study Population
n=135 Participants
All patients randomized into the study
|
|---|---|
|
Age, Continuous
|
60.4 Years
STANDARD_DEVIATION 7.93 • n=5 Participants
|
|
Gender
Female
|
40 Participants
n=5 Participants
|
|
Gender
Male
|
95 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14Population: Intent to treat (ITT) population: all randomized patients who took at least 1 dose of study drug and had at least 1 baseline and 1 post-baseline assessment of value of FEV1
FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose
Outcome measures
| Measure |
Placebo
n=97 Participants
Placebo twice daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=99 Participants
Aclidinium bromide 200 μg + formoterol fumurate 12 μg fixed dose combination (FDC) twice daily
|
Aclidinium 200 μg / Formoterol 6 μg
n=100 Participants
Aclidinium bromide 200 μg + formoterol fumurate 6 μg fixed dose combination (FDC) twice daily
|
Aclidinium 200 μg
n=96 Participants
Aclidinium bromide 200 μg twice daily
|
Formoterol 12 μg
n=99 Participants
Formoterol fumurate 12 μg twice daily
|
|---|---|---|---|---|---|
|
Change From Baseline in Normalized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12h) After Morning Study Drug Administration at Day 14
|
-0.041 Liters
Standard Error 0.021
|
0.180 Liters
Standard Error 0.021
|
0.193 Liters
Standard Error 0.021
|
0.139 Liters
Standard Error 0.021
|
0.100 Liters
Standard Error 0.021
|
SECONDARY outcome
Timeframe: Day 14Population: Intent to treat (ITT) population: all randomized patients who took at least 1 dose of study drug and had at least 1 baseline and 1 post-baseline assessment of value of FEV1
FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes
Outcome measures
| Measure |
Placebo
n=100 Participants
Placebo twice daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=99 Participants
Aclidinium bromide 200 μg + formoterol fumurate 12 μg fixed dose combination (FDC) twice daily
|
Aclidinium 200 μg / Formoterol 6 μg
n=100 Participants
Aclidinium bromide 200 μg + formoterol fumurate 6 μg fixed dose combination (FDC) twice daily
|
Aclidinium 200 μg
n=96 Participants
Aclidinium bromide 200 μg twice daily
|
Formoterol 12 μg
n=99 Participants
Formoterol fumurate 12 μg twice daily
|
|---|---|---|---|---|---|
|
Change From Baseline in Morning Pre-dose FEV1 at Day 14
|
-0.059 Liters
Standard Error 0.020
|
0.042 Liters
Standard Error 0.020
|
0.067 Liters
Standard Error 0.020
|
0.072 Liters
Standard Error 0.020
|
0.027 Liters
Standard Error 0.020
|
SECONDARY outcome
Timeframe: 0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14Population: Intent to treat (ITT) population: all randomized patients who took at least 1 dose of study drug and had at least 1 baseline and 1 post-baseline assessment of value of FEV1
FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose
Outcome measures
| Measure |
Placebo
n=100 Participants
Placebo twice daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=99 Participants
Aclidinium bromide 200 μg + formoterol fumurate 12 μg fixed dose combination (FDC) twice daily
|
Aclidinium 200 μg / Formoterol 6 μg
n=100 Participants
Aclidinium bromide 200 μg + formoterol fumurate 6 μg fixed dose combination (FDC) twice daily
|
Aclidinium 200 μg
n=96 Participants
Aclidinium bromide 200 μg twice daily
|
Formoterol 12 μg
n=99 Participants
Formoterol fumurate 12 μg twice daily
|
|---|---|---|---|---|---|
|
Change From Baseline in Morning Peak FEV1 at Day 14
|
0.052 Liters
Standard Error 0.023
|
0.335 Liters
Standard Error 0.023
|
0.347 Liters
Standard Error 0.023
|
0.255 Liters
Standard Error 0.023
|
0.255 Liters
Standard Error 0.023
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Aclidinium 200 μg / Formoterol 12 μg
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Aclidinium 200 μg / Formoterol 6 μg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Aclidinium 200 μg
Serious events: 0 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
Serious adverse events
| Measure |
Placebo
n=101 participants at risk
Placebo twice daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=101 participants at risk
Aclidinium bromide 200 μg + formoterol fumurate 12 μg fixed dose combination (FDC) twice daily
|
Aclidinium 200 μg / Formoterol 6 μg
n=102 participants at risk
Aclidinium bromide 200 μg + formoterol fumurate 6 μg fixed dose combination (FDC) twice daily
|
Aclidinium 200 μg
n=100 participants at risk
Aclidinium bromide 200 μg twice daily
|
Formoterol 12 μg
n=101 participants at risk
Formoterol fumurate 12 μg twice daily
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary mass
|
0.00%
0/101 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.99%
1/101 • Number of events 1 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.00%
0/102 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.00%
0/100 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.00%
0/101 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/101 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.99%
1/101 • Number of events 1 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.00%
0/102 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.00%
0/100 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.00%
0/101 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/101 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.00%
0/101 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.00%
0/102 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.00%
0/100 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
0.99%
1/101 • Number of events 1 • Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Publication and/or presentation whether complete or partial, of any part of the data or results of this trial will be subject to revision and written agreement between the investigator and sponsor
- Publication restrictions are in place
Restriction type: OTHER