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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01437397




Registration number
NCT01437397
Ethics application status
Date submitted
19/09/2011
Date registered
20/09/2011
Date last updated
23/03/2017

Titles & IDs
Public title
Efficacy, Safety and Tolerability of Aclidinium Bromide/Formoterol Fumarate Compared With Aclidinium Bromide and Formoterol Fumarate in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Scientific title
A Phase III, Randomized, Double-blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Tolerability of Two Fixed Dose Combinations of Aclidinium Bromide/Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo for 24- Weeks Treatment in Patients With Moderate to Severe, Stable Chronic Obstructive Pulmonary Disease (COPD).
Secondary ID [1] 0 0
LAC-MD-31
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Aclidinium Bromide/Formoterol Fumarate
Treatment: Drugs - Aclidinium Bromide/Formoterol Fumarate
Treatment: Drugs - Aclidinium Bromide
Treatment: Drugs - Formoterol Fumarate
Treatment: Drugs - Placebo

Experimental: 1 - Aclidinium/formoterol Fixed Dose Combination (FDC) 400/12µg

Experimental: 2 - Aclidinium/formoterol Fixed Dose Combination (FDC) 400/6µg

Active Comparator: 3 - Aclidinium monotherapy 400 µg

Active Comparator: 4 - Formoterol monotherapy 12 µg

Placebo Comparator: 5 - Placebo


Treatment: Drugs: Aclidinium Bromide/Formoterol Fumarate
Inhaled Aclidinium/formoterol FDC 400/12µg, twice per day

Treatment: Drugs: Aclidinium Bromide/Formoterol Fumarate
Inhaled Aclidinium/formoterol FDC 400/6µg, twice per day

Treatment: Drugs: Aclidinium Bromide
Inhaled Aclidinium 400 µg, twice per day

Treatment: Drugs: Formoterol Fumarate
Inhaled Formoterol 12 µg, twice per day

Treatment: Drugs: Placebo
Inhaled dose-matched placebo, twice per day

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1)
Timepoint [1] 0 0
Week 24 of treatment
Primary outcome [2] 0 0
Change From Baseline in Morning Trough Forced Expiratory Volume in One Second (FEV1)
Timepoint [2] 0 0
Week 24 of treatment
Secondary outcome [1] 0 0
Change in Transition Dyspnea Index (TDI) Focal Score - The TDI measures the change from baseline in severity of breathlessness in symptomatic patients. The TDI contains a rating for 3 categories (functional impairment, magnitude of task, magnitude of effort).TDI scale ranges from -3 (major deterioration) to +3 (major improvement) including a 0 score to indicate "no change". The 3 categories are added to obtain a focal score ranging from -9 (including 0) to +9.
Timepoint [1] 0 0
Week 24 of treatment
Secondary outcome [2] 0 0
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score - St George's Respiratory Questionnaire (SGRQ) measures COPD-specific health outcomes and consists of 2 parts with 3 dimension scores (a symptom score and an activity and impacts score). SGRQ total score is the sum of these scores and ranges from 0 (best health status) to 100 (worst health status).
Timepoint [2] 0 0
Week 24 of treatment

Eligibility
Key inclusion criteria
- Male or female patients at least 40 years of age

- Current or former cigarette smoker with a cigarette smoking history of at least 10
pack-years

- A diagnosis of stable moderate to severe COPD and stable airway obstruction as defined
by the GOLD guidelines and stable airway obstruction. Patients had to have a
postbronchodilator FEV1/FVC ratio < 70% at Visit 1 (GOLD, 2010)

- Post-albuterol/salbutamol FEV1 values = 30% and < 80% of predicted value. FEV1 was
measured at the Screening Visit (Visit 1) 10 to 15 minutes after inhalation of
albuterol/salbutamol. Predicted normal used for calculation purposes were based on
National Health and Nutrition Examination Survey III predicted values (Hankinson et
al, 1999)

- Able to perform acceptable and repeatable pulmonary function testing for FEV1
according to ATS/ERS criteria (Miller et al, 2005) at Screening Visit (Visit 1) and
throughout their participation in the trial

- Negative serum ß-human chorionic gonadotropin pregnancy test at Visit 1 and must have
been using hormonal contraceptives or a barrier method plus a spermicidal agent;
otherwise at least 1-year postmenopausal or surgically sterile, defined as having a
hysterectomy or tubal ligation (applied to female patients only)

- Judged by the Principal Investigator to be in otherwise good stable health based on
medical history, physical examination, ECGs, and routine laboratory data evaluations

- Patients previously randomized in an aclidinium monotherapy trial were permitted as
long as it had been at least 6 months since the completion of their previous trial
participation

- Able to understand the study procedures and be willing to participate in the study as
indicated by signing the informed consent
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Hospitalization for an acute COPD exacerbation within 3 months before Visit 1

- Any respiratory tract infection (including the upper respiratory tract) or COPD
exacerbation in the 6 weeks before Visit 1. Patients who developed a respiratory tract
infection or COPD exacerbation during the washout or run-in period were discontinued
from the study before randomization

- Any clinically significant respiratory conditions other than COPD, including active
tuberculosis, history of interstitial lung disease, pulmonary thromboembolic disease,
history of a1-antitrypsin deficiency, pulmonary resection, lung volume surgery, or any
other thoracic surgery during the past 12 months, history of bronchiectasis secondary
to respiratory diseases other than COPD (eg, cystic fibrosis, Kartagener syndrome),
post organ transplantation, or expected to require thoracotomy or other lung surgery
during the study

- Clinical history suggesting that the patient had asthma as opposed to COPD (Study
Physician was to be contacted to discuss eligibility, if necessary)

- Chronic use of oxygen therapy = 15 hours/day

- Body mass index(BMI) = 40 kg/m2

- Patients who intended to start a pulmonary rehabilitation program during the trial
were excluded, as well as those who finished or started it within 3 months prior to
Screening Visit

- Clinically significant cardiovascular conditions including: myocardial infarction
within the previous 6 months; newly diagnosed arrhythmia within the previous 3 months;
unstable angina; unstable arrhythmia that had required changes in pharmacological
therapy or other intervention within the previous 6 months; the presence of an
automated implantable cardioverter-defibrillator; history of thoracic surgery within
the past year before screening; hospitalization within the previous 12 months for
heart failure of New York Heart Association functional class III (marked limitation of
physical activity and only comfortable at rest, less than ordinary activity causes
fatigue, palpitation or dyspnea), or class IV (unable to carry out any physical
activity without discomfort) (Criteria Committee of the New York Heart Association
criteria, 1994)

- Any uncontrolled infection that may have placed the patient at risk resulting from
human immunodeficiency virus, active hepatitis and/or patients with diagnosed active
tuberculosis

- QTcB > 470 msec in the resting ECGs performed at Screening (Visit 1), as indicated in
the centralized ECG vendor generated report. Patients who were on a stable dose of
medication that may prolong the QTc, but had a documented, stable, and normal QTc,
could have been considered

- QTcB > 470 msec in the resting ECGs performed before randomization at Visit 2, as
indicated in the paper tracing generated by the Sponsor-provided ECG equipment

- Clinically relevant abnormalities in the results of the clinical laboratory tests, in
ECG parameters other than QTc, or in the physical examination or vital signs at Visit
1 except for those related to COPD

- History of drug or alcohol abuse within the previous 5 years

- Any other serious or uncontrolled physical or mental condition/disease that, as judged
by the Investigator, could have placed the patient at higher risk derived from his/her
participation in the study, could have confounded the results of the study, or would
be likely to have prevented the patient from complying with the requirements of the
study or completing the study. If there was a history of such disease, but the
condition had been stable for more than 1 year and was judged by the Investigator not
to interfere with the patient's participation in the study, the patient may have been
included, with the documented approval of the Study Physician

- History of hypersensitivity reaction to inhaled anticholinergics, beta-2 agonists,
sympathomimetic amines, or inhaled medication or any component thereof (including
report of paradoxical bronchospasm) or a history of acute urinary retention,
symptomatic benign prostatic hyperplasia, bladder neck obstruction, or narrow-angle
glaucoma. (Note: Patients who had well controlled, stable, asymptomatic benign
prostatic hyperplasia were not to be excluded)

- Sitting, resting systolic BP = 160 mm Hg and/or diastolic BP = 100 mm Hg at Visit 1
and Visit 2

- Unable to use a multidose dry-powder inhaler or a pressurized metered-dose inhaler

- Treatment with any other investigational product within 30 days (or 6 half-lives,
whichever was longer) before Visit 1

- Previous participation in a clinical trial with aclidinium bromide in an FDC therapy

- Pregnant or breastfeeding

- Current diagnosis of cancer (present in the patient) other than basal or squamous cell
skin cancer. Patients who had a history of cancer must have been cleared before Visit
1 (Screening) on a case-by-case basis

- Patients who did not maintain regular day/night, waking/sleeping cycles (eg, night
shift workers)

- Patients who intended to use any concomitant medication not permitted by this protocol
or who had not undergone the required washout period for a particular prohibited
medication (Appendix III of the protocol, which can be found in Appendix 16.1.1 of
this report)

- Patients who were unlikely to be compliant with study requirements (eg, take their
medication, complete their electronic diaries, attend clinic at the required times)

- Patients who were employees or relatives of employees of the investigative study
center, FRI, Almirall, SA, or Pharmaceutical Product Development (PPD, Inc.)

- Patients who had any other conditions that, in the Investigator's opinion, might have
indicated the patient to be unsuitable for the study or supported excluding the
patient from the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Forest Investigative Site 1991 - New Lambton
Recruitment hospital [2] 0 0
Forest Investigative Site 1987 - Redcliffe
Recruitment hospital [3] 0 0
Forest Investigative Site 1973 - Woolloongabba
Recruitment hospital [4] 0 0
Forest Investigative Site 1981 - Bedford Park
Recruitment hospital [5] 0 0
Forest Investigative Site 1990 - Daw Park
Recruitment hospital [6] 0 0
Forest Investigative Site 2251 - Toorak Gardens
Recruitment hospital [7] 0 0
Forest Investigative Site 2250 - Clayton
Recruitment hospital [8] 0 0
Forest Investigative Site 1972 - Fitzroy
Recruitment hospital [9] 0 0
Forest Investigative Site 1986 - Geelong
Recruitment hospital [10] 0 0
Forest Investigative Site 1985 - Parkville
Recruitment hospital [11] 0 0
Forest Investigative Site 2253 - Adelaide
Recruitment postcode(s) [1] 0 0
2305 - New Lambton
Recruitment postcode(s) [2] 0 0
4020 - Redcliffe
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5042 - Bedford Park
Recruitment postcode(s) [5] 0 0
5041 - Daw Park
Recruitment postcode(s) [6] 0 0
5065 - Toorak Gardens
Recruitment postcode(s) [7] 0 0
3168 - Clayton
Recruitment postcode(s) [8] 0 0
3011 - Fitzroy
Recruitment postcode(s) [9] 0 0
3220 - Geelong
Recruitment postcode(s) [10] 0 0
3050 - Parkville
Recruitment postcode(s) [11] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Idaho
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Louisiana
Country [12] 0 0
United States of America
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Maine
Country [13] 0 0
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Maryland
Country [14] 0 0
United States of America
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Massachusetts
Country [15] 0 0
United States of America
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Michigan
Country [16] 0 0
United States of America
State/province [16] 0 0
Minnesota
Country [17] 0 0
United States of America
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Mississippi
Country [18] 0 0
United States of America
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Missouri
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United States of America
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Montana
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United States of America
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Nebraska
Country [21] 0 0
United States of America
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Nevada
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New Jersey
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United States of America
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New Mexico
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United States of America
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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Utah
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Vermont
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Virginia
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Washington
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United States of America
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West Virginia
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Canada
State/province [39] 0 0
British Columbia
Country [40] 0 0
Canada
State/province [40] 0 0
Manitoba
Country [41] 0 0
Canada
State/province [41] 0 0
Ontario
Country [42] 0 0
Canada
State/province [42] 0 0
Quebec
Country [43] 0 0
Canada
State/province [43] 0 0
Saskatchewan
Country [44] 0 0
New Zealand
State/province [44] 0 0
Auckland
Country [45] 0 0
New Zealand
State/province [45] 0 0
Christchurch
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New Zealand
State/province [46] 0 0
Dunedin
Country [47] 0 0
New Zealand
State/province [47] 0 0
Hamilton
Country [48] 0 0
New Zealand
State/province [48] 0 0
Tauranga
Country [49] 0 0
New Zealand
State/province [49] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this Phase III study is to assess the maintenance bronchodilator effects of
the fixed dose combination versus monotherapies. This study will also assess the effects of
the fixed dose combination in terms of COPD symptoms, disease related health status and the
long-term safety and tolerability of the fixed dose combination. This study will include a 24
week treatment period, preceding by a run-in period, followed by a two week follow up visit.
All patients will be randomized to one of four treatment arms or placebo.
Trial website
https://clinicaltrials.gov/show/NCT01437397
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Esther Garcia, MD
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications