Trial Outcomes & Findings for Aclidinium/Formoterol Fixed Combination Dose Finding Study (NCT NCT00626522)
NCT ID: NCT00626522
Last Updated: 2016-11-16
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
808 participants
Primary outcome timeframe
Baseline and treatment Week 4
Results posted on
2016-11-16
Participant Flow
The study was conducted in a total of 81 sites: 21 in Russia, 13 in Poland, 8 in India, 8 in Romania, 6 in Australia, 5 in Taiwan, 5 in the Czech Republic, 5 in New Zealand, 4 in Hungary, 3 in Malaysia and 3 in Slovakia The first patient was screened in February 2008 and the last patient visit was in November 2008
A total of 808 patients were screened and 566 were randomized into the study Among 242 patients who failed to be randomized, the main reason for screen failure was non-fulfillment of one or more study entry criteria (156 patients), followed by subject's personal request (32 patients)
Participant milestones
| Measure |
Aclidinium 200 μg / Formoterol 6 μg
Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 12 μg
Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 18 μg
Aclidinium bromide 200 μg + formoterol fumarate 18 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg
Aclidinium bromide 200 μg once-daily
|
Formoterol 12 μg
Formoterol fumarate 12 μg once-daily
|
Placebo
Placebo once-daily
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
121
|
120
|
125
|
76
|
65
|
59
|
|
Overall Study
COMPLETED
|
115
|
113
|
117
|
74
|
58
|
57
|
|
Overall Study
NOT COMPLETED
|
6
|
7
|
8
|
2
|
7
|
2
|
Reasons for withdrawal
| Measure |
Aclidinium 200 μg / Formoterol 6 μg
Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 12 μg
Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 18 μg
Aclidinium bromide 200 μg + formoterol fumarate 18 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg
Aclidinium bromide 200 μg once-daily
|
Formoterol 12 μg
Formoterol fumarate 12 μg once-daily
|
Placebo
Placebo once-daily
|
|---|---|---|---|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Adverse Event
|
2
|
1
|
2
|
0
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
5
|
5
|
0
|
4
|
1
|
|
Overall Study
COPD exacerbation
|
0
|
0
|
0
|
1
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Inconsistent reason reported
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Non-fulfilment of in/exclusion criteria
|
1
|
0
|
1
|
1
|
0
|
0
|
Baseline Characteristics
Aclidinium/Formoterol Fixed Combination Dose Finding Study
Baseline characteristics by cohort
| Measure |
Aclidinium 200 μg / Formoterol 6 μg
n=121 Participants
Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=120 Participants
Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 18 μg
n=125 Participants
Aclidinium bromide 200 μg + formoterol fumarate 18 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg
n=76 Participants
Aclidinium bromide 200 μg once-daily
|
Formoterol 12 μg
n=65 Participants
Formoterol fumarate 12 μg once-daily
|
Placebo
n=59 Participants
Placebo once-daily
|
Total
n=566 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
62.9 Years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
63.6 Years
STANDARD_DEVIATION 8.9 • n=7 Participants
|
63.9 Years
STANDARD_DEVIATION 8.1 • n=5 Participants
|
63.7 Years
STANDARD_DEVIATION 9.3 • n=4 Participants
|
64.0 Years
STANDARD_DEVIATION 9.8 • n=21 Participants
|
60.7 Years
STANDARD_DEVIATION 7.8 • n=8 Participants
|
63.3 Years
STANDARD_DEVIATION 8.8 • n=8 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
15 Participants
n=8 Participants
|
123 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
91 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
96 Participants
n=5 Participants
|
60 Participants
n=4 Participants
|
54 Participants
n=21 Participants
|
44 Participants
n=8 Participants
|
443 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline and treatment Week 4Population: ITT Population defined as all randomised patients who took at least one dose of investigational medicinal product and had at least the baseline and one post-baseline efficacy assessments
Outcome measures
| Measure |
Aclidinium 200 μg / Formoterol 6 μg
n=112 Participants
Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=111 Participants
Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 18 μg
n=115 Participants
Aclidinium bromide 200 μg + formoterol fumarate 18 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg
n=71 Participants
Aclidinium bromide 200 μg once-daily
|
Formoterol 12 μg
n=54 Participants
Formoterol fumarate 12 μg once-daily
|
Placebo
n=55 Participants
Placebo once-daily
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-12 hr
|
0.170 Liters
Interval 0.128 to 0.213
|
0.219 Liters
Interval 0.176 to 0.262
|
0.230 Liters
Interval 0.187 to 0.273
|
0.075 Liters
Interval 0.021 to 0.129
|
0.099 Liters
Interval 0.037 to 0.161
|
-0.036 Liters
Interval -0.097 to 0.025
|
SECONDARY outcome
Timeframe: Baseline and treatment Week 4Population: ITT Population defined as all randomised patients who took at least one dose of investigational medicinal product and had at least the baseline and one post-baseline efficacy assessments
Outcome measures
| Measure |
Aclidinium 200 μg / Formoterol 6 μg
n=117 Participants
Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=117 Participants
Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 18 μg
n=121 Participants
Aclidinium bromide 200 μg + formoterol fumarate 18 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg
n=73 Participants
Aclidinium bromide 200 μg once-daily
|
Formoterol 12 μg
n=63 Participants
Formoterol fumarate 12 μg once-daily
|
Placebo
n=56 Participants
Placebo once-daily
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1)
|
0.042 Liters
Interval 0.001 to 0.084
|
0.085 Liters
Interval 0.044 to 0.127
|
0.044 Liters
Interval 0.003 to 0.085
|
-0.017 Liters
Interval -0.7 to 0.036
|
0.014 Liters
Interval -0.043 to 0.071
|
-0.031 Liters
Interval -0.091 to 0.029
|
SECONDARY outcome
Timeframe: Baseline and treatment Week 4Population: ITT Population defined as all randomised patients who took at least one dose of investigational medicinal product and had at least the baseline and one post-baseline efficacy assessments
Outcome measures
| Measure |
Aclidinium 200 μg / Formoterol 6 μg
n=121 Participants
Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=120 Participants
Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 18 μg
n=124 Participants
Aclidinium bromide 200 μg + formoterol fumarate 18 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg
n=75 Participants
Aclidinium bromide 200 μg once-daily
|
Formoterol 12 μg
n=65 Participants
Formoterol fumarate 12 μg once-daily
|
Placebo
n=58 Participants
Placebo once-daily
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)
|
0.294 Liters
Interval 0.25 to 0.338
|
0.357 Liters
Interval 0.313 to 0.401
|
0.349 Liters
Interval 0.305 to 0.393
|
0.184 Liters
Interval 0.128 to 0.24
|
0.216 Liters
Interval 0.156 to 0.276
|
0.044 Liters
Interval -0.019 to 0.108
|
SECONDARY outcome
Timeframe: Baseline and treatment Week 4Population: ITT Population defined as all randomised patients who took at least one dose of investigational medicinal product and had at least the baseline and one post-baseline efficacy assessments
Outcome measures
| Measure |
Aclidinium 200 μg / Formoterol 6 μg
n=121 Participants
Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=120 Participants
Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 18 μg
n=124 Participants
Aclidinium bromide 200 μg + formoterol fumarate 18 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg
n=75 Participants
Aclidinium bromide 200 μg once-daily
|
Formoterol 12 μg
n=65 Participants
Formoterol fumarate 12 μg once-daily
|
Placebo
n=56 Participants
Placebo once-daily
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-3 hr
|
0.197 Liters
Interval 0.158 to 0.236
|
0.256 Liters
Interval 0.217 to 0.295
|
0.250 Liters
Interval 0.211 to 0.289
|
0.088 Liters
Interval 0.038 to 0.138
|
0.134 Liters
Interval 0.081 to 0.188
|
-0.033 Liters
Interval -0.091 to 0.024
|
SECONDARY outcome
Timeframe: Baseline and treatment Week 4Population: ITT Population defined as all randomised patients who took at least one dose of investigational medicinal product and had at least the baseline and one post-baseline efficacy assessments
Outcome measures
| Measure |
Aclidinium 200 μg / Formoterol 6 μg
n=115 Participants
Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=112 Participants
Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 18 μg
n=115 Participants
Aclidinium bromide 200 μg + formoterol fumarate 18 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg
n=72 Participants
Aclidinium bromide 200 μg once-daily
|
Formoterol 12 μg
n=56 Participants
Formoterol fumarate 12 μg once-daily
|
Placebo
n=55 Participants
Placebo once-daily
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-6 hr
|
0.206 Liters
Interval 0.164 to 0.249
|
0.266 Liters
Interval 0.223 to 0.309
|
0.272 Liters
Interval 0.229 to 0.314
|
0.094 Liters
Interval 0.04 to 0.148
|
0.137 Liters
Interval 0.076 to 0.198
|
-0.033 Liters
Interval -0.094 to 0.029
|
Adverse Events
Aclidinium 200 μg / Formoterol 6 μg
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Aclidinium 200 μg / Formoterol 12 μg
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Aclidinium 200 μg / Formoterol 18 μg
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
Aclidinium 200 μg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Formoterol 12 μg
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Aclidinium 200 μg / Formoterol 6 μg
n=121 participants at risk
Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=120 participants at risk
Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 18 μg
n=125 participants at risk
Aclidinium bromide 200 μg + formoterol fumarate 18 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg
n=76 participants at risk
Aclidinium bromide 200 μg once-daily
|
Formoterol 12 μg
n=65 participants at risk
Formoterol fumarate 12 μg once-daily
|
Placebo
n=59 participants at risk
Placebo once-daily
|
|---|---|---|---|---|---|---|
|
Investigations
Electrocardiogram abnormal
|
0.83%
1/121 • Up to Day 38
|
0.00%
0/120 • Up to Day 38
|
0.00%
0/125 • Up to Day 38
|
0.00%
0/76 • Up to Day 38
|
0.00%
0/65 • Up to Day 38
|
0.00%
0/59 • Up to Day 38
|
|
Infections and infestations
Infective exacerbation of chronic obstructive pulmonary disease
|
0.00%
0/121 • Up to Day 38
|
0.83%
1/120 • Up to Day 38
|
0.00%
0/125 • Up to Day 38
|
0.00%
0/76 • Up to Day 38
|
0.00%
0/65 • Up to Day 38
|
0.00%
0/59 • Up to Day 38
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/121 • Up to Day 38
|
0.00%
0/120 • Up to Day 38
|
0.80%
1/125 • Up to Day 38
|
0.00%
0/76 • Up to Day 38
|
0.00%
0/65 • Up to Day 38
|
0.00%
0/59 • Up to Day 38
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/121 • Up to Day 38
|
0.00%
0/120 • Up to Day 38
|
0.80%
1/125 • Up to Day 38
|
0.00%
0/76 • Up to Day 38
|
0.00%
0/65 • Up to Day 38
|
0.00%
0/59 • Up to Day 38
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/121 • Up to Day 38
|
0.00%
0/120 • Up to Day 38
|
0.80%
1/125 • Up to Day 38
|
0.00%
0/76 • Up to Day 38
|
0.00%
0/65 • Up to Day 38
|
0.00%
0/59 • Up to Day 38
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/121 • Up to Day 38
|
0.00%
0/120 • Up to Day 38
|
0.00%
0/125 • Up to Day 38
|
0.00%
0/76 • Up to Day 38
|
1.5%
1/65 • Up to Day 38
|
0.00%
0/59 • Up to Day 38
|
Other adverse events
| Measure |
Aclidinium 200 μg / Formoterol 6 μg
n=121 participants at risk
Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 12 μg
n=120 participants at risk
Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg / Formoterol 18 μg
n=125 participants at risk
Aclidinium bromide 200 μg + formoterol fumarate 18 μg fixed dose combination (FDC) once-daily
|
Aclidinium 200 μg
n=76 participants at risk
Aclidinium bromide 200 μg once-daily
|
Formoterol 12 μg
n=65 participants at risk
Formoterol fumarate 12 μg once-daily
|
Placebo
n=59 participants at risk
Placebo once-daily
|
|---|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.7%
2/121 • Up to Day 38
|
0.83%
1/120 • Up to Day 38
|
2.4%
3/125 • Up to Day 38
|
5.3%
4/76 • Up to Day 38
|
7.7%
5/65 • Up to Day 38
|
3.4%
2/59 • Up to Day 38
|
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