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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00626522




Registration number
NCT00626522
Ethics application status
Date submitted
21/02/2008
Date registered
29/02/2008
Date last updated
16/11/2016

Titles & IDs
Public title
Aclidinium/Formoterol Fixed Combination Dose Finding Study
Scientific title
A Randomised, 4-week, Placebo-controlled, Double-blind, 6 Arm Parallel Group, Dose-finding Clinical Trial, to Assess the Efficacy, Safety and Pharmacokinetics of Three Different Doses of Formoterol Combined With the Inhaled Anticholinergic Aclidinium Bromide, Aclidinium Bromide Monotherapy and Formoterol Monotherapy All Administrated Once Daily by Inhalation Via Almirall Inhaler in Patients With Stable Moderate to Severe Chronic Obstructive Pulmonary Disease.
Secondary ID [1] 0 0
2007-004435-30
Secondary ID [2] 0 0
M/273FO/23
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease (COPD) 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 and formoterol
Treatment: Drugs - Aclidinium bromide and formoterol placebo

Experimental: 1 -

Experimental: 2 -

Experimental: 3 -

Placebo Comparator: 4 -

Placebo Comparator: 5 -

Placebo Comparator: 6 -


Treatment: Drugs: Aclidinium bromide and formoterol
once daily

Treatment: Drugs: Aclidinium bromide and formoterol placebo
once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-12 hr
Timepoint [1] 0 0
Baseline and treatment Week 4
Secondary outcome [1] 0 0
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1)
Timepoint [1] 0 0
Baseline and treatment Week 4
Secondary outcome [2] 0 0
Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)
Timepoint [2] 0 0
Baseline and treatment Week 4
Secondary outcome [3] 0 0
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-3 hr
Timepoint [3] 0 0
Baseline and treatment Week 4
Secondary outcome [4] 0 0
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) for 0-6 hr
Timepoint [4] 0 0
Baseline and treatment Week 4

Eligibility
Key inclusion criteria
1. Adult males or non-pregnant, non-lactating females aged between 40 and 80 years old,
both inclusive. Women of childbearing potential were allowed to enter the trial only
if they used two medically approved contraceptive measures (ie, mechanical and
pharmacological).

(A female was considered to be of childbearing potential unless she had a
hysterectomy, was at least one year post-menopause or had undergone tubal ligation.
All women of childbearing potential were to have a negative serum pregnancy test at
the Screening Visit).

2. Patients with a clinical diagnosis of stable moderate to severe COPD (stages II and
III) according to the GOLD 2006 classification (http://www.goldcopd.com).

3. Current or ex-cigarette smoker with a smoking history of at least 10 pack-years.

Pack-years were calculated by dividing the number of cigarettes smoked per day by 20
(the number of cigarettes in a pack) and multiplying this figure by the number of
years a person had smoked. For example, a person who smoked 40 cigarettes a day and
had smoked for 10 years would have had a 20 pack-year smoking history (40 cigarettes
per day ÷ 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history).

Patients smoking other tobacco types were not allowed, unless they met the cigarette
criterion as well.

4. Patients whose Forced Expiratory Volume in 1 second (FEV1) at the Screening Visit
measured between 30-45 minutes post inhalation of 400 µg of salbutamol was 30% =FEV1
<80% of the predicted normal value (ie, 100 x Post-salbutamol FEV1/Predicted FEV1 <80%
and =30%). (Predicted normal values used for calculation purposes were to be based on
European Community for Steel and Coal predicted values)

5. Patients whose FEV1/Forced Vital Capacity (FVC) at the Screening Visit measured
between 30- 45 minutes post inhalation of 400 µg of salbutamol was <70% (ie, 100 x
Post-salbutamol FEV1/FVC <70%).

6. Patients whose COPD symptoms and FEV1 values at the time of randomisation were stable
compared to the Screening Visit, according to the Investigator's medical judgment.

7. Patients who were eligible and able to participate in the trial and who consented to
do so in writing after the purpose and nature of the investigation had been explained.
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History or current diagnosis of asthma, allergic rhinitis or atopy, or
exercise-induced bronchospasm.

2. Eosinophil count =600 cells/mm3.

3. Clinically significant respiratory conditions at the time of Screening Visit defined
as:

- Use of long-term oxygen therapy >5 h/day,

- Known active tuberculosis,

- History of interstitial lung or pulmonary thromboembolic disease,

- Pulmonary resection during the past 12 months,

- History of life-threatening COPD,

- History of bronchiectasis secondary to respiratory diseases others than COPD (eg,
cystic fibrosis, Kartagener's syndrome, etc),

- Patients who in the Investigator's opinion may have needed to stop or start
pulmonary rehabilitation or undergo a thoracotomy during the trial,

4. Hospitalisation due to COPD exacerbation, up to the 3 months prior to the Screening
Visit.

5. Signs of a COPD exacerbation or respiratory infection (including the upper respiratory
tract), up to the 6 weeks prior to the Screening Visit.

6. Clinically significant cardiovascular conditions at the time of Screening Visit
defined as:

- Myocardial infarction within the previous 6 months,

- Unstable arrhythmia which has required changes in the pharmacological therapy or
other intervention within the previous 12 months, or newly diagnosed arrhythmia
within the previous 3 months.

- Hospitalisation within the previous 12 months for heart failure functional
classes III (marked limitation of activity and only comfortable at rest) and IV
(need of complete rest, confinement to bed or chair, discomfort at any physical
activity and presence of symptoms at rest) as per the New York Heart Association
classification (www.americanheart.org)

- Thoracic surgery within the previous 24 months

7. Presence of symptomatic prostatic hypertrophy and/or bladder neck obstruction.
(However, patients who had a diagnosis of these conditions but without symptoms due to
stable concomitant medication for its treatment were allowed to enter trial).

8. Presence of narrow-angle glaucoma.

9. History of untoward reactions or known hypersensitivity to inhaled anticholinergics
(including aclidinium bromide), ß2 adrenergic agonists or inhaled medication or any
component thereof (including report of paradoxical bronchospasm).

10. Life expectancy of less than 1 year.

11. Prolonged QT interval corrected using Bazett's formula (QTcB) interval (>470 msec) in
any of the ECGs performed before randomisation, and/or the use of drugs which may have
induced its prolongation.

12. Clinically relevant abnormalities in laboratory results, ECG parameters (other than
QTcB), or physical examination if the abnormality defines a disease state listed as an
exclusion criterion, except for those related to COPD.

13. Clinically significant diseases other than COPD, which, in the opinion of the
Investigator, may have put the patient at risk because of the participation in the
trial; or diseases which may have influenced the results of the study or the patient's
ability to take part in it.

14. Patients who did not maintain regular day/night, waking/sleeping cycles (eg, night
shift workers were to be excluded).

15. Patients who intended to use any concomitant medication not permitted by the protocol
or who had not undergone the required wash-out period for a particular prohibited
medication.

16. Patients who were unable or unlikely to be cooperative with the study requirements of
taking the medication, completion of the Patient Diary and attending the clinic for
study visits.

17. Patients who were unable to properly use a dry powder or pressurised metered-dose
inhalers (pMDI) inhaler device and/or to perform acceptable and reproducible
spirometry measurements as per the ATS/ERS standards (Standardisation of lung function
test, 2005 20).

18. History of drug and/or alcohol abuse or addiction during the previous 2 years.

19. Previous participation in another clinical trial with any investigational medicinal
product 6 weeks prior to the Screening Visit. (Patients who had participated in a
previous clinical trial with aclidinium bromide (Almirall product code LAS34273) were
to be allowed to participate in this study provided that the above criterion was
fulfilled. This circumstance was to be specifically recorded on the eCRF).

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
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
1/02/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2008
Sample size
Target
Accrual to date
Final
808
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Taichung
Recruitment hospital [2] 0 0
Research Site - Taipei
Recruitment postcode(s) [1] 0 0
- Taichung
Recruitment postcode(s) [2] 0 0
- Taipei
Recruitment outside Australia
Country [1] 0 0
Czech Republic
State/province [1] 0 0
Moscow
Country [2] 0 0
Poland
State/province [2] 0 0
Saint Petersburg
Country [3] 0 0
Poland
State/province [3] 0 0
St-Petersburg
Country [4] 0 0
Poland
State/province [4] 0 0
St. Petersburg
Country [5] 0 0
Russian Federation
State/province [5] 0 0
Moscow
Country [6] 0 0
Russian Federation
State/province [6] 0 0
Saint Petersburg
Country [7] 0 0
Russian Federation
State/province [7] 0 0
Saint-Petersburg
Country [8] 0 0
Russian Federation
State/province [8] 0 0
Saratov
Country [9] 0 0
Russian Federation
State/province [9] 0 0
Yaroslavl

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

Ethics approval
Ethics application status

Summary
Brief summary
The study seeks to determine the optimal dose of the Aclidinium/Formoterol combination for
investigation in Phase III clinical trials
Trial website
https://clinicaltrials.gov/ct2/show/NCT00626522
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00626522