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Efficacy and Safety of Aclidinium Bromide 400 µg Compared to Placebo and to Tiotropium Bromide in Patients With Stable Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

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ClinicalTrials.gov Identifier: NCT01462929
Recruitment Status : Completed
First Posted : November 1, 2011
Results First Posted : May 22, 2013
Last Update Posted : January 4, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease (COPD)
Interventions Drug: Aclidinium bromide
Drug: Tiotropium
Drug: Placebo
Enrollment 414
Recruitment Details This study was conducted in 49 sites investigators in 4 countries (3 sites in the Czech Republic, 23 in Germany, 8 in Hungary and 15 in Poland). 8 sites (3 in Germany, 3 in Hungary and 2 in Poland) did not randomise any patients. The first patient was screened in Oct 2011 and the last patient visit was in Mar 2012.
Pre-assignment Details Patients fulfilling inclusion/exclusion criteria at the time of the screening visit were entered into a run-in period of 14-21 days to assess disease stability.
Arm/Group Title Aclidinium Bromide 400 µg BID Tiotropium 18 μg Once-daily Placebo
Hide Arm/Group Description

Aclidinium bromide 400 µg administered twice per day

Dosage form: Dry powder. Route of administration: Oral inhalation by Genuair multidose dry powder inhaler.

Dose and regimen: 1 puff of 400 micrograms in the morning (09:00 ± 1h) and in the evening (21:00 ± 1h)

AND

1 capsule of placebo in the morning (09:00 ± 1h) via oral inhalation by HandiHaler single-dose dry powder inhaler.

Tiotropium 18 μg administered once daily

Dosage form: Dry powder hard gelatin capsule. Route of administration: Oral inhalation by HandiHaler single-dose dry powder inhaler.

Dose and regimen: 1 capsule (18 μg) in the morning (09:00 ± 1h)

AND

1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) via oral inhalation by Genuair multidose dry powder inhaler.

Placebo

Route of administration:

Oral inhalation by Genuair multidose dry powder inhaler. 1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) AND Oral inhalation by HandiHaler single-dose dry powder inhaler. 1 capsule of placebo in the morning (09:00 ± 1h).

Period Title: Overall Study
Started 171 158 85
Completed 166 154 80
Not Completed 5 4 5
Reason Not Completed
Adverse Event             3             3             4
Withdrawal by Subject             2             1             0
Lack of Efficacy             0             0             1
Arm/Group Title Aclidinium Bromide 400 µg BID Tiotropium 18 μg Once-daily Placebo Total
Hide Arm/Group Description

Aclidinium bromide 400 µg administered twice per day

Dosage form: Dry powder. Route of administration: Oral inhalation by Genuair multidose dry powder inhaler.

Dose and regimen: 1 puff of 400 micrograms in the morning (09:00 ± 1h) and in the evening (21:00 ± 1h)

AND

1 capsule of placebo in the morning (09:00 ± 1h) via oral inhalation by HandiHaler single-dose dry powder inhaler.

Tiotropium 18 μg administered once daily

Dosage form: Dry powder hard gelatin capsule. Route of administration: Oral inhalation by HandiHaler single-dose dry powder inhaler.

Dose and regimen: 1 capsule (18 μg) in the morning (09:00 ± 1h)

AND

1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) via oral inhalation by Genuair multidose dry powder inhaler.

Placebo

Route of administration:

Oral inhalation by Genuair multidose dry powder inhaler. 1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) AND Oral inhalation by HandiHaler single-dose dry powder inhaler. 1 capsule of placebo in the morning (09:00 ± 1h).

Total of all reporting groups
Overall Number of Baseline Participants 171 158 85 414
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 171 participants 158 participants 85 participants 414 participants
61.8  (8.2) 62.8  (7.9) 62.2  (8.2) 62.3  (8.1)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 158 participants 85 participants 414 participants
Female
57
  33.3%
42
  26.6%
37
  43.5%
136
  32.9%
Male
114
  66.7%
116
  73.4%
48
  56.5%
278
  67.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 171 participants 158 participants 85 participants 414 participants
Hungary 18 16 10 44
Czech Republic 5 3 3 11
Poland 64 58 32 154
Germany 84 81 40 205
1.Primary Outcome
Title Change From Baseline in Normalised Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over the 24-h Period After 6 Weeks of Treatment
Hide Description Change from baseline in normalised FEV1 area under the curve over the 24-h period immediately after morning Investigational Medicinal Product administration (AUC0-24h ) after 6 weeks on treatment. The normalised AUC were calculated by means of a trapezoidal method, dividing by the corresponding time interval.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT) population: patients who took at least 1 dose of Investigational Medicinal Product and had at least a baseline FEV1 assessment and at least one post-baseline FEV1 value
Arm/Group Title Aclidinium Bromide 400 µg BID Tiotropium 18 μg Once-daily Placebo
Hide Arm/Group Description:

Aclidinium bromide 400 µg administered twice per day

Dosage form: Dry powder. Route of administration: Oral inhalation by Genuair multidose dry powder inhaler.

Dose and regimen: 1 puff of 400 micrograms in the morning (09:00 ± 1h) and in the evening (21:00 ± 1h)

AND

1 capsule of placebo in the morning (09:00 ± 1h) via oral inhalation by HandiHaler single-dose dry powder inhaler.

Tiotropium 18 μg administered once daily

Dosage form: Dry powder hard gelatin capsule. Route of administration: Oral inhalation by HandiHaler single-dose dry powder inhaler.

Dose and regimen: 1 capsule (18 μg) in the morning (09:00 ± 1h)

AND

1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) via oral inhalation by Genuair multidose dry powder inhaler.

Placebo

Route of administration:

Oral inhalation by Genuair multidose dry powder inhaler. 1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) AND Oral inhalation by HandiHaler single-dose dry powder inhaler. 1 capsule of placebo in the morning (09:00 ± 1h).

Overall Number of Participants Analyzed 170 158 85
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.065  (0.017) 0.055  (0.018) -0.085  (0.023)
2.Secondary Outcome
Title Change From Baseline in Normalised FEV1 Area Under the Curve Over the 12-h Night-time Period After 6 Weeks of Treatment
Hide Description Change from baseline in normalised FEV1 area under the curve over the 12-h night-time period (AUC12-24) after 6 weeks of treatment. The normalised AUC were calculated by means of a trapezoidal method, dividing by the corresponding time interval.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT) population: patients who took at least 1 dose of Investigational Medicinal Product and had at least a baseline FEV1 assessment and at least one post-baseline FEV1 value
Arm/Group Title Aclidinium Bromide 400 µg BID Tiotropium 18 μg Once-daily Placebo
Hide Arm/Group Description:

Aclidinium bromide 400 µg administered twice per day

Dosage form: Dry powder. Route of administration: Oral inhalation by Genuair multidose dry powder inhaler.

Dose and regimen: 1 puff of 400 micrograms in the morning (09:00 ± 1h) and in the evening (21:00 ± 1h)

AND

1 capsule of placebo in the morning (09:00 ± 1h) via oral inhalation by HandiHaler single-dose dry powder inhaler.

Tiotropium 18 μg administered once daily

Dosage form: Dry powder hard gelatin capsule. Route of administration: Oral inhalation by HandiHaler single-dose dry powder inhaler.

Dose and regimen: 1 capsule (18 μg) in the morning (09:00 ± 1h)

AND

1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) via oral inhalation by Genuair multidose dry powder inhaler.

Placebo

Route of administration:

Oral inhalation by Genuair multidose dry powder inhaler. 1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) AND Oral inhalation by HandiHaler single-dose dry powder inhaler. 1 capsule of placebo in the morning (09:00 ± 1h).

Overall Number of Participants Analyzed 170 158 85
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.032  (0.017) -0.006  (0.018) -0.128  (0.024)
Time Frame 8 Weeks
Adverse Event Reporting Description A follow-up was performed by means of a visit or a phone contact, as considered appropriate, 2 weeks (±3 days) after the last Investigational Medicinal Product dose administration in order to assess new or ongoing AEs, abnormal values of study variables (laboratory evaluations, BP or ECG) or COPD exacerbation.
 
Arm/Group Title Aclidinium Bromide 400 µg BID Tiotropium 18 μg Once-daily Placebo
Hide Arm/Group Description

Aclidinium bromide 400 µg administered twice per day

Dosage form: Dry powder. Route of administration: Oral inhalation by Genuair multidose dry powder inhaler.

Dose and regimen: 1 puff of 400 micrograms in the morning (09:00 ± 1h) and in the evening (21:00 ± 1h)

AND

1 capsule of placebo in the morning (09:00 ± 1h) via oral inhalation by HandiHaler single-dose dry powder inhaler.

Tiotropium 18 μg administered once daily

Dosage form: Dry powder hard gelatin capsule. Route of administration: Oral inhalation by HandiHaler single-dose dry powder inhaler.

Dose and regimen: 1 capsule (18 μg) in the morning (09:00 ± 1h)

AND

1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) via oral inhalation by Genuair multidose dry powder inhaler.

Placebo

Route of administration:

Oral inhalation by Genuair multidose dry powder inhaler. 1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) AND Oral inhalation by HandiHaler single-dose dry powder inhaler. 1 capsule of placebo in the morning (09:00 ± 1h).

All-Cause Mortality
Aclidinium Bromide 400 µg BID Tiotropium 18 μg Once-daily Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Aclidinium Bromide 400 µg BID Tiotropium 18 μg Once-daily Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/171 (1.75%)      4/158 (2.53%)      0/85 (0.00%)    
Cardiac disorders       
Angina Unstable  1  0/171 (0.00%)  0 1/158 (0.63%)  1 0/85 (0.00%)  0
Ventricular Extrasystoles  1  0/171 (0.00%)  0 1/158 (0.63%)  1 0/85 (0.00%)  0
Gastrointestinal disorders       
Dysphagia  1  1/171 (0.58%)  1 0/158 (0.00%)  0 0/85 (0.00%)  0
Pancreatitis Acute  1  0/171 (0.00%)  0 1/158 (0.63%)  1 0/85 (0.00%)  0
Infections and infestations       
Pneumonia  1  1/171 (0.58%)  1 0/158 (0.00%)  0 0/85 (0.00%)  0
Viral Infection  1  1/171 (0.58%)  1 0/158 (0.00%)  0 0/85 (0.00%)  0
Nervous system disorders       
Transient Ischaemic Attack  1  1/171 (0.58%)  1 0/158 (0.00%)  0 0/85 (0.00%)  0
Psychiatric disorders       
Mental Disorder  1  1/171 (0.58%)  1 0/158 (0.00%)  0 0/85 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Pneumonia Aspiration  1  1/171 (0.58%)  1 0/158 (0.00%)  0 0/85 (0.00%)  0
Chronic Obstructive Pulmonary Disease  1 [1]  0/171 (0.00%)  0 1/158 (0.63%)  1 0/85 (0.00%)  0
Vascular disorders       
Peripheral Vascular Disorder  1  0/171 (0.00%)  0 1/158 (0.63%)  1 0/85 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
[1]
Per protocol, only COPD exacerbations (worsening of COPD symptoms for at least 2 consecutive days that required a change in the patient’s COPD treatment) were reported as AEs
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aclidinium Bromide 400 µg BID Tiotropium 18 μg Once-daily Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/171 (9.36%)      17/158 (10.76%)      6/85 (7.06%)    
Infections and infestations       
Nasopharyngitis  1  11/171 (6.43%)  8/158 (5.06%)  2/85 (2.35%) 
Nervous system disorders       
Headache  1  6/171 (3.51%)  11/158 (6.96%)  4/85 (4.71%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: AstraZeneca Clinical
Organization: Study Information Center
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01462929     History of Changes
Other Study ID Numbers: M/34273/39
First Submitted: October 28, 2011
First Posted: November 1, 2011
Results First Submitted: March 27, 2013
Results First Posted: May 22, 2013
Last Update Posted: January 4, 2017