Trial Outcomes & Findings for Efficacy and Safety of Aclidinium Bromide at Two Dose Levels Versus Placebo Administered in Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT NCT01001494)
NCT ID: NCT01001494
Last Updated: 2017-01-04
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
828 participants
Primary outcome timeframe
Baseline and Week 24
Results posted on
2017-01-04
Participant Flow
This study was conducted at 103 sites (100/103 randomised patients), 10 sites in the Czech Republic, 5 in France, 17 in Germany, 13 in Hungary, 3 in Italy, 1 in Peru, 21 in Poland, 10 in the Russian Federation, 5 in Spain, 13 in South Africa and 5 in the Ukraine. The first patient was screened in Oct 2009 and the last patient visit was in Nov 2010.
Patients fulfilling inclusion/exclusion criteria at the time of the Screening Visit were entered into a run-in period of 14±3 days to assess patient's disease stability.
Participant milestones
| Measure |
Aclidinium Bromide 200 μg Bid
Aclidinium bromide 200 μg twice-daily via inhalation
|
Aclidinium Bromide 400 μg Bid
Aclidinium bromide 400 μg twice-daily via inhalation
|
Placebo
Placebo via inhalation
|
|---|---|---|---|
|
Overall Study
STARTED
|
277
|
269
|
273
|
|
Overall Study
COMPLETED
|
253
|
252
|
232
|
|
Overall Study
NOT COMPLETED
|
24
|
17
|
41
|
Reasons for withdrawal
| Measure |
Aclidinium Bromide 200 μg Bid
Aclidinium bromide 200 μg twice-daily via inhalation
|
Aclidinium Bromide 400 μg Bid
Aclidinium bromide 400 μg twice-daily via inhalation
|
Placebo
Placebo via inhalation
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
8
|
4
|
6
|
|
Overall Study
Protocol Violation
|
0
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
9
|
7
|
17
|
|
Overall Study
COPD exacerbation
|
3
|
4
|
5
|
|
Overall Study
Lack of Efficacy
|
2
|
0
|
8
|
|
Overall Study
Other
|
0
|
1
|
3
|
Baseline Characteristics
Efficacy and Safety of Aclidinium Bromide at Two Dose Levels Versus Placebo Administered in Chronic Obstructive Pulmonary Disease (COPD) Patients
Baseline characteristics by cohort
| Measure |
Aclidinium Bromide 200 μg Bid
n=277 Participants
Aclidinium bromide 200 μg twice-daily via inhalation
|
Aclidinium Bromide 400 μg Bid
n=269 Participants
Aclidinium bromide 400 μg twice-daily via inhalation
|
Placebo
n=273 Participants
Placebo via inhalation
|
Total
n=819 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=113 Participants
|
0 Participants
n=163 Participants
|
0 Participants
n=160 Participants
|
0 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
169 Participants
n=113 Participants
|
161 Participants
n=163 Participants
|
179 Participants
n=160 Participants
|
509 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
108 Participants
n=113 Participants
|
108 Participants
n=163 Participants
|
94 Participants
n=160 Participants
|
310 Participants
n=483 Participants
|
|
Age, Continuous
|
62.3 years
STANDARD_DEVIATION 7.8 • n=113 Participants
|
62.9 years
STANDARD_DEVIATION 8.4 • n=163 Participants
|
62.0 years
STANDARD_DEVIATION 8.0 • n=160 Participants
|
62.4 years
STANDARD_DEVIATION 8.0 • n=483 Participants
|
|
Gender
Female
|
96 Participants
n=113 Participants
|
87 Participants
n=163 Participants
|
84 Participants
n=160 Participants
|
267 Participants
n=483 Participants
|
|
Gender
Male
|
181 Participants
n=113 Participants
|
182 Participants
n=163 Participants
|
189 Participants
n=160 Participants
|
552 Participants
n=483 Participants
|
|
Region of Enrollment
Spain
|
6 participants
n=113 Participants
|
7 participants
n=163 Participants
|
5 participants
n=160 Participants
|
18 participants
n=483 Participants
|
|
Region of Enrollment
Ukraine
|
8 participants
n=113 Participants
|
8 participants
n=163 Participants
|
11 participants
n=160 Participants
|
27 participants
n=483 Participants
|
|
Region of Enrollment
Russian Federation
|
14 participants
n=113 Participants
|
16 participants
n=163 Participants
|
15 participants
n=160 Participants
|
45 participants
n=483 Participants
|
|
Region of Enrollment
Italy
|
4 participants
n=113 Participants
|
2 participants
n=163 Participants
|
2 participants
n=160 Participants
|
8 participants
n=483 Participants
|
|
Region of Enrollment
France
|
8 participants
n=113 Participants
|
8 participants
n=163 Participants
|
8 participants
n=160 Participants
|
24 participants
n=483 Participants
|
|
Region of Enrollment
Hungary
|
35 participants
n=113 Participants
|
30 participants
n=163 Participants
|
32 participants
n=160 Participants
|
97 participants
n=483 Participants
|
|
Region of Enrollment
Czech Republic
|
22 participants
n=113 Participants
|
20 participants
n=163 Participants
|
19 participants
n=160 Participants
|
61 participants
n=483 Participants
|
|
Region of Enrollment
Poland
|
79 participants
n=113 Participants
|
74 participants
n=163 Participants
|
77 participants
n=160 Participants
|
230 participants
n=483 Participants
|
|
Region of Enrollment
South Africa
|
46 participants
n=113 Participants
|
47 participants
n=163 Participants
|
48 participants
n=160 Participants
|
141 participants
n=483 Participants
|
|
Region of Enrollment
Germany
|
55 participants
n=113 Participants
|
57 participants
n=163 Participants
|
56 participants
n=160 Participants
|
168 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 24Population: Intention-to-treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and who had a baseline and at least 1 post-baseline FEV1 assessment.
Outcome measures
| Measure |
Aclidinium Bromide 200 μg Bid
n=277 Participants
Aclidinium bromide 200 μg twice-daily via inhalation
|
Aclidinium Bromide 400 μg Bid
n=269 Participants
Aclidinium bromide 400 μg twice-daily via inhalation
|
Placebo
n=273 Participants
Placebo via inhalation
|
|---|---|---|---|
|
Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment
|
0.026 Liters
Standard Error 0.016
|
0.055 Liters
Standard Error 0.016
|
-0.073 Liters
Standard Error 0.016
|
PRIMARY outcome
Timeframe: Baseline and Week 12Population: Intention-to-treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and who had a baseline and at least 1 post-baseline FEV1 assessment.
Outcome measures
| Measure |
Aclidinium Bromide 200 μg Bid
n=277 Participants
Aclidinium bromide 200 μg twice-daily via inhalation
|
Aclidinium Bromide 400 μg Bid
n=269 Participants
Aclidinium bromide 400 μg twice-daily via inhalation
|
Placebo
n=273 Participants
Placebo via inhalation
|
|---|---|---|---|
|
Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 12 on Treatment
|
0.030 Liters
Standard Error 0.014
|
0.058 Liters
Standard Error 0.015
|
-0.047 Liters
Standard Error 0.015
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Intention-to-treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and who had a baseline and at least 1 post-baseline FEV1 assessment.
Outcome measures
| Measure |
Aclidinium Bromide 200 μg Bid
n=277 Participants
Aclidinium bromide 200 μg twice-daily via inhalation
|
Aclidinium Bromide 400 μg Bid
n=269 Participants
Aclidinium bromide 400 μg twice-daily via inhalation
|
Placebo
n=273 Participants
Placebo via inhalation
|
|---|---|---|---|
|
Change From Baseline in Peak Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment
|
0.206 Liters
Standard Error 0.017
|
0.231 Liters
Standard Error 0.017
|
0.022 Liters
Standard Error 0.017
|
SECONDARY outcome
Timeframe: Week 24Population: Intention-to-treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and who had a baseline and at least 1 post-baseline FEV1 assessment.
Number of patients achieving a clinically meaningful improvement (≥1-unit) in Transition Dyspnoea Index (TDI) focal score at Week 24 on Treatment
Outcome measures
| Measure |
Aclidinium Bromide 200 μg Bid
n=270 Participants
Aclidinium bromide 200 μg twice-daily via inhalation
|
Aclidinium Bromide 400 μg Bid
n=262 Participants
Aclidinium bromide 400 μg twice-daily via inhalation
|
Placebo
n=257 Participants
Placebo via inhalation
|
|---|---|---|---|
|
Percentage of Patients Who Achieved at Least a 1-unit Decrease From Baseline in TDI Focal Score at Week 24 on Treatment
Yes (% Patients with a 1-unit decrease)
|
53.3 Percentage of participants
|
56.9 Percentage of participants
|
45.5 Percentage of participants
|
|
Percentage of Patients Who Achieved at Least a 1-unit Decrease From Baseline in TDI Focal Score at Week 24 on Treatment
No (% Patients with a 1-unit decrease)
|
46.7 Percentage of participants
|
43.1 Percentage of participants
|
54.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: Intention-to-treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and who had a baseline and at least 1 post-baseline FEV1 assessment.
Number of patients who achieved a clinically meaningful improvement (≥4-units) in Saint George Respiratory Questionnaire (SGRQ) total score at week 24 on treatment
Outcome measures
| Measure |
Aclidinium Bromide 200 μg Bid
n=275 Participants
Aclidinium bromide 200 μg twice-daily via inhalation
|
Aclidinium Bromide 400 μg Bid
n=269 Participants
Aclidinium bromide 400 μg twice-daily via inhalation
|
Placebo
n=271 Participants
Placebo via inhalation
|
|---|---|---|---|
|
Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at Week 24 on Treatment
Yes (% Patients with 4-unit decrease)
|
56.0 Percentage of participants
|
57.3 Percentage of participants
|
41.0 Percentage of participants
|
|
Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at Week 24 on Treatment
No (% Patients with 4-unit decrease)
|
44.0 Percentage of participants
|
42.8 Percentage of participants
|
59.0 Percentage of participants
|
Adverse Events
Aclidinium Bromide 200 μg Bid
Serious events: 12 serious events
Other events: 44 other events
Deaths: 0 deaths
Aclidinium Bromide 400 μg Bid
Serious events: 15 serious events
Other events: 38 other events
Deaths: 0 deaths
Placebo
Serious events: 15 serious events
Other events: 56 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Aclidinium Bromide 200 μg Bid
n=277 participants at risk
Aclidinium bromide 200 μg twice-daily via inhalation
|
Aclidinium Bromide 400 μg Bid
n=269 participants at risk
Aclidinium bromide 400 μg twice-daily via inhalation
|
Placebo
n=273 participants at risk
Placebo via inhalation
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease
|
1.1%
3/277 • Number of events 4 • 24 Weeks
|
0.74%
2/269 • Number of events 2 • 24 Weeks
|
3.7%
10/273 • Number of events 10 • 24 Weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Cardiac disorders
Myocardial ischaemia
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Cardiac disorders
Angina Pectoris
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Cardiac disorders
Cardiac discomfort
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Cardiac disorders
Cardiac failure acute
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Cardiac disorders
Sick sinus syndrome
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Cardiac disorders
Left vetricular failure
|
0.00%
0/277 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.37%
1/273 • Number of events 1 • 24 Weeks
|
|
Cardiac disorders
Myocardial infarction
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Injury, poisoning and procedural complications
Ligament ruptures
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/277 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.37%
1/273 • Number of events 1 • 24 Weeks
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Infections and infestations
Pneumonia
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.37%
1/273 • Number of events 1 • 24 Weeks
|
|
Infections and infestations
Bronchopneumonia
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma stage III
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mycosis fungoides
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign lung neoplasm
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic neuroendocrine tumour
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Musculoskeletal and connective tissue disorders
Invertebral disc protrusion
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Vascular disorders
Arteriosclerosis
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Vascular disorders
Aortis stenosis
|
0.00%
0/277 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.37%
1/273 • Number of events 1 • 24 Weeks
|
|
Vascular disorders
Subclavian atery stenosis
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Nervous system disorders
Demyelinating polyneuropathy
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Ear and labyrinth disorders
Mixed deafness
|
0.00%
0/277 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.37%
1/273 • Number of events 1 • 24 Weeks
|
|
Gastrointestinal disorders
Subileus
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/277 • 24 Weeks
|
0.37%
1/269 • Number of events 1 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Psychiatric disorders
Completed suicide
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.36%
1/277 • Number of events 1 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.00%
0/273 • 24 Weeks
|
|
Skin and subcutaneous tissue disorders
Erythema nodosum
|
0.00%
0/277 • 24 Weeks
|
0.00%
0/269 • 24 Weeks
|
0.37%
1/273 • Number of events 1 • 24 Weeks
|
Other adverse events
| Measure |
Aclidinium Bromide 200 μg Bid
n=277 participants at risk
Aclidinium bromide 200 μg twice-daily via inhalation
|
Aclidinium Bromide 400 μg Bid
n=269 participants at risk
Aclidinium bromide 400 μg twice-daily via inhalation
|
Placebo
n=273 participants at risk
Placebo via inhalation
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructivce pulmonary disease
|
15.9%
44/277 • 24 Weeks
|
14.1%
38/269 • 24 Weeks
|
20.5%
56/273 • 24 Weeks
|
|
Nervous system disorders
Headache
|
10.8%
30/277 • 24 Weeks
|
12.3%
33/269 • 24 Weeks
|
8.1%
22/273 • 24 Weeks
|
|
Infections and infestations
Nasopharyngitis
|
11.6%
32/277 • 24 Weeks
|
11.2%
30/269 • 24 Weeks
|
8.4%
23/273 • 24 Weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee All the information related to this clinical trial is considered strictly confidential and is the property of Almirall. This information will not be given to a third party without the written consent of Almirall. 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 Almirall.
- Publication restrictions are in place
Restriction type: OTHER