Clinical Trials List
Protocol NumberM-AS464-30 (AZ code: D6570C00002)
2016-01-01 - 2017-04-25
Others
Recruiting1
Terminated5
Study ended1
ICD-10J44.9
Chronic obstructive pulmonary disease, unspecified
ICD-9496
Chronic airways obstruction, not elsewhere classified
A 24-week Treatment, Randomised, Parallel-group, Double blinded, DoubleDummy, Multicenter Study to Assess the Efficacy and Safety of Aclidinium bromide/Formoterol fumarate compared with Individual Components and Placebo and Aclidinium bromide compared with Placebo when Administered to Patients with Stable Chronic Obstructive Pulmonary Disease
-
Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
-
Sponsor
AstraZeneca AB
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 游騰仁 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Completed
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Wei-Zhi Chen Division of Thoracic Medicine
- 潘聖衛 Division of Thoracic Medicine
- 何莉櫻 Division of Thoracic Medicine
- WEI-JUIN SU Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Completed
Principal Investigator
Co-Principal Investigator
- Hsu Wu-Huei 未分科
Audit
None
Co-Principal Investigator
- 程味兒 Division of General Internal Medicine
- Chen Chia-Hung 未分科
- Chih-Yen Tu Division of General Internal Medicine
- Shuo-Chueh Chen 未分科
- Yu-Chao Lin 未分科
- 梁信杰 未分科
- 廖偉志 未分科
- Chih-Ching Yen Division of General Internal Medicine
- Chia-Hsiang Li 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Stable Chronic Obstructive Pulmonary Disease
Objectives
Primary objectives
To assess the bronchodilatory effect of Aclidinium bromide 400 µg /Formoterol
fumarate 12 µg compared to individual components and placebo when administered
twice daily via inhalation to COPD patients.
To assess the bronchodilatory effect of Aclidinium bromide 400 µg compared to
placebo when administered twice daily via inhalation to COPD patients.
Secondary objectives
To assess the benefits of Aclidinium bromide 400 µg /Formoterol fumarate 12 µg in
COPD symptoms, disease-related health status and COPD exacerbations compared to
placebo, when administered BID via inhalation to COPD patients.
To assess the benefits of Aclidinium bromide 400 µg in COPD symptoms, diseaserelated health status and COPD exacerbations compared to placebo, when
administered BID via inhalation to COPD patients.
Test Drug
Aclidinium bromide/Formoterol fumarate
Active Ingredient
Aclidinium bromide/Formoterol fumarate
Dosage Form
inhalation powder
Dosage
400/12
Endpoints
The primary efficacy variables are the following:
Change from baseline in 1-hour morning post-dose dose FEV1 of Aclidinium bromide
400 µg/Formoterol fumarate 12 µg compared to Aclidinium bromide at Week 24.
Change from baseline in morning pre-dose (trough) FEV1 of Aclidinium bromide 400
µg/Formoterol fumarate 12 µg compared to Formoterol fumarate at Week 24.
Change from baseline in trough FEV1 of Aclidinium bromide 400 µg compared to
placebo at Week 24.
Change from baseline in 1-hour morning post-dose dose FEV1 of Aclidinium bromide
400 µg/Formoterol fumarate 12 µg compared to Aclidinium bromide at Week 24.
Change from baseline in morning pre-dose (trough) FEV1 of Aclidinium bromide 400
µg/Formoterol fumarate 12 µg compared to Formoterol fumarate at Week 24.
Change from baseline in trough FEV1 of Aclidinium bromide 400 µg compared to
placebo at Week 24.
Inclution Criteria
1. Adult male or non-pregnant, non-lactating female patients aged ≥40
Explanatory note: A female is considered to be of childbearing potential unless
is at least one year post-menopausal or permanently sterilised (e.g. tubal
occlusion, hysterectomy, bilateral salpingectomy). Women of childbearing
potential are allowed to enter the trial if they show to have a negative
pregnancy test at the Screening Visit and are using, during the last two months
before the Screening Visit and during the whole duration of the trial, at least
one medically approved and highly effective method of birth control defined as
those, alone or in combination, which result in a low failure rate (i.e less than
1% per year) when used consistently and correctly. Male participants are not
requested to use contraception methods during thier participation on the trial.
2. Patients with a diagnosis of COPD (GOLD guidelines, 2015) for a period of at least 6
months prior to Visit 1 (screening).
3. Patients with moderate to severe stable COPD (Stage II or Stage III, according to
GOLD Guidelines 2015) at Visit 1: post-bronchodilator FEV1 ≥30% and < 80% and
post-bronchodilator FEV1/FVC < 70%
Explanatory note: “post” means FEV1 and FVC between 10 to 15 minutes after
inhalation of 400 μg of salbutamol from acceptable and repeatable pulmonary
function testing according to the American Thoracic Society (ATS)/European
Respiratory Society (ERS) 2005 criteria. Predicted normal values to be used for
calculation purposes are based on the Global Lung Function Initiative predicted
values (Quanjer et al. 2012).
4. Current or former smokers with a smoking history of ≥ 10 pack-years.
Explanatory notes:
a. Former smoker condition defined as having quit smoking ≥ 6 months
before Visit 1 (Screening).
b. Pack-years is 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 has smoked. For example, a person who smokes 40 cigarettes a day and has smoked for 10 years
would have 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). In case of intermittent smoking/non-smoking periods, packyears is calculated by summing all periods pack-years.
c. Patients smoking other tobacco types will not be allowed, unless they
meet the cigarette criterion as well.
5. Patients able to perform repeatable pulmonary function testing for FEV1 according to
the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005
criteria at Visit 1(screening ).
6. Patients who understand the study procedures and are willing to participate in the study
as indicated by signing the informed consent.
Explanatory note: A female is considered to be of childbearing potential unless
is at least one year post-menopausal or permanently sterilised (e.g. tubal
occlusion, hysterectomy, bilateral salpingectomy). Women of childbearing
potential are allowed to enter the trial if they show to have a negative
pregnancy test at the Screening Visit and are using, during the last two months
before the Screening Visit and during the whole duration of the trial, at least
one medically approved and highly effective method of birth control defined as
those, alone or in combination, which result in a low failure rate (i.e less than
1% per year) when used consistently and correctly. Male participants are not
requested to use contraception methods during thier participation on the trial.
2. Patients with a diagnosis of COPD (GOLD guidelines, 2015) for a period of at least 6
months prior to Visit 1 (screening).
3. Patients with moderate to severe stable COPD (Stage II or Stage III, according to
GOLD Guidelines 2015) at Visit 1: post-bronchodilator FEV1 ≥30% and < 80% and
post-bronchodilator FEV1/FVC < 70%
Explanatory note: “post” means FEV1 and FVC between 10 to 15 minutes after
inhalation of 400 μg of salbutamol from acceptable and repeatable pulmonary
function testing according to the American Thoracic Society (ATS)/European
Respiratory Society (ERS) 2005 criteria. Predicted normal values to be used for
calculation purposes are based on the Global Lung Function Initiative predicted
values (Quanjer et al. 2012).
4. Current or former smokers with a smoking history of ≥ 10 pack-years.
Explanatory notes:
a. Former smoker condition defined as having quit smoking ≥ 6 months
before Visit 1 (Screening).
b. Pack-years is 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 has smoked. For example, a person who smokes 40 cigarettes a day and has smoked for 10 years
would have 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). In case of intermittent smoking/non-smoking periods, packyears is calculated by summing all periods pack-years.
c. Patients smoking other tobacco types will not be allowed, unless they
meet the cigarette criterion as well.
5. Patients able to perform repeatable pulmonary function testing for FEV1 according to
the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005
criteria at Visit 1(screening ).
6. Patients who understand the study procedures and are willing to participate in the study
as indicated by signing the informed consent.
Exclusion Criteria
1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff
and/or site staff) or patients employed by or relatives of the employees of the site or
sponsor.
2. Previous enrolment or randomisation in the present study
3. History or current diagnosis of asthma.
4. Any respiratory tract infection (including the upper respiratory tract) or COPD
exacerbation (including the mild COPD exacerbation) within 6 weeks prior to
screening or during the run-in period.
5. Patients hospitalized for COPD exacerbation (an emergency room visit for longer than
24 hours will be considered a hospitalization) within 3 months prior to screening and
during the run-in period.
6. Clinically significant respiratory conditions other than COPD
Explanatory note: Clinically significant respiratory conditions, some examples
are:
a. Known active tuberculosis.
b. History of interstitial lung disease or massive pulmonary
thromboembolic disease.
c. Pulmonary resection or lung volume reduction surgery.
d. History of lung transplantation.
e. Patients who in the Investigator’s opinion might have needed
thoracotomy or other lung surgery during the study.
f. Clinically significant bronchiectasis.
g. Known α1-antitrypsin deficiency.
7. Patients who in the Investigator’s opinion may need to start a pulmonary rehabilitation
program during the study and/or patients who started/finished it within 3 months prior
to screening.
8. Use of long-term oxygen therapy (≥15 hours/day).
9. Patient who does not maintain regular day/night, waking/sleeping cycles including
night shift workers.
Explanatory note: patients with symptomatic sleep apnoea syndrome, any
disease related to sleep disturbances such as restless-legs syndrome or
somnambulism are to be excluded from the study. However, the use of
continuous positive airway pressure is not an exclusion criterion
10. Clinically significant cardiovascular conditions:
Explanatory note: Clinically significant cardiovascular conditions, some
examples are
a. Myocardial infarction within the 6 months prior to screening.
b. Thoracic surgery within 12 months prior to Visit 1 (screening).
c. Unstable angina or unstable arrhythmia which had required changes in
the pharmacological therapy or other intervention within 12 months
prior to Visit 1 (screening), or newly diagnosed arrhythmia within the 3
months prior to screening.
d. Hospitalization within 12 months prior to screening 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.
11. Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypo-or
hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled or untreated
hypertension.
12. Patients with QT corrected interval (QTc) using Fridericia formula (QTcF)
(QTc=QT/RR1/3) >470 msec as indicated in the centralised reading report assessed at
Screening (Visit 1).
13. Patients with clinically significant abnormalities in the clinical laboratory tests, ECG
parameters (other than QTcF) or in the physical examination at Visit 1 (screening).
14. Patients with abnormal liver function tests defined as AST, ALT, or total bilirubin ≥
2.5 times upper limit of normal ranges at screening
15. Patient with known non-controlled history of infection with human immunodeficiency
virus and/or active hepatitis
Explanatory note: Active hepatitis is defined as clinical symptoms associated
with chronic portal inflammation with regional necrosis and fibrosis, which
may progress to nodular postnecrotic cirrhosis or patients with antibody to
hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg) test
with positive results or antihepatitis C virus (HCV) antibody and HCV
recombinant immunoblot assay HCV positive tests or genetic material
(ribonucleic acid) testing positive results.
16. Patient with a history of hypersensitivity reaction to inhaled anticholinergic drugs,
sympathomimetic amines, inhaled medication or any component thereof.
17. Patient with known narrow-angle glaucoma, symptomatic bladder neck obstruction,
acute urinary retention, or patients with symptomatic non-stable prostatic hypertrophy.
Explanatory note: Patients with well-controlled, stable, asymptomatic benign
prostatic hypertrophy are not excluded.
18. History of malignancy of any organ system (including lung cancer), treated or
untreated, within the past 5 years other than basal or squamous cell skin cancer.
Explanatory note: Patients are excluded whether or not there is evidence of
local recurrence or metastases.
19. Any other serious or uncontrolled physical or mental dysfunction.
Explanatory note: as judged by the Investigator, the dysfunction could place the
patient at a higher risk as a result of his/her participation in the study, or
confound the results of the study, or would be likely to prevent the patient from
complying with the requirements of the study or completing the study
20. Patients with a history (within 2 years prior to Visit 1 (screening) of drug and/or
alcohol abuse that may prevent study compliance based on the Investigator judgment.
21. Patients unlikely to be cooperative or cannot comply with the study procedures
Explanatory note: patients who may have difficulties following the treatment,
completing the patient diary, or attending the clinic at the required times, or
unable to properly use a DPI or pressured metered dose inhaler device, or
performing spirometry measurements.
22. Patients treated with any investigational drug within 30 days (or 6 half-lives,
whichever is longer) prior to screening.
23. 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.
24. Patients unable to give consent, or patients of consenting age but under guardianship,
or vulnerable patients.
25. Any other conditions that, in the Investigator’s opinion, might have indicated the
patient to be unsuitable for the study.
and/or site staff) or patients employed by or relatives of the employees of the site or
sponsor.
2. Previous enrolment or randomisation in the present study
3. History or current diagnosis of asthma.
4. Any respiratory tract infection (including the upper respiratory tract) or COPD
exacerbation (including the mild COPD exacerbation) within 6 weeks prior to
screening or during the run-in period.
5. Patients hospitalized for COPD exacerbation (an emergency room visit for longer than
24 hours will be considered a hospitalization) within 3 months prior to screening and
during the run-in period.
6. Clinically significant respiratory conditions other than COPD
Explanatory note: Clinically significant respiratory conditions, some examples
are:
a. Known active tuberculosis.
b. History of interstitial lung disease or massive pulmonary
thromboembolic disease.
c. Pulmonary resection or lung volume reduction surgery.
d. History of lung transplantation.
e. Patients who in the Investigator’s opinion might have needed
thoracotomy or other lung surgery during the study.
f. Clinically significant bronchiectasis.
g. Known α1-antitrypsin deficiency.
7. Patients who in the Investigator’s opinion may need to start a pulmonary rehabilitation
program during the study and/or patients who started/finished it within 3 months prior
to screening.
8. Use of long-term oxygen therapy (≥15 hours/day).
9. Patient who does not maintain regular day/night, waking/sleeping cycles including
night shift workers.
Explanatory note: patients with symptomatic sleep apnoea syndrome, any
disease related to sleep disturbances such as restless-legs syndrome or
somnambulism are to be excluded from the study. However, the use of
continuous positive airway pressure is not an exclusion criterion
10. Clinically significant cardiovascular conditions:
Explanatory note: Clinically significant cardiovascular conditions, some
examples are
a. Myocardial infarction within the 6 months prior to screening.
b. Thoracic surgery within 12 months prior to Visit 1 (screening).
c. Unstable angina or unstable arrhythmia which had required changes in
the pharmacological therapy or other intervention within 12 months
prior to Visit 1 (screening), or newly diagnosed arrhythmia within the 3
months prior to screening.
d. Hospitalization within 12 months prior to screening 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.
11. Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypo-or
hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled or untreated
hypertension.
12. Patients with QT corrected interval (QTc) using Fridericia formula (QTcF)
(QTc=QT/RR1/3) >470 msec as indicated in the centralised reading report assessed at
Screening (Visit 1).
13. Patients with clinically significant abnormalities in the clinical laboratory tests, ECG
parameters (other than QTcF) or in the physical examination at Visit 1 (screening).
14. Patients with abnormal liver function tests defined as AST, ALT, or total bilirubin ≥
2.5 times upper limit of normal ranges at screening
15. Patient with known non-controlled history of infection with human immunodeficiency
virus and/or active hepatitis
Explanatory note: Active hepatitis is defined as clinical symptoms associated
with chronic portal inflammation with regional necrosis and fibrosis, which
may progress to nodular postnecrotic cirrhosis or patients with antibody to
hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg) test
with positive results or antihepatitis C virus (HCV) antibody and HCV
recombinant immunoblot assay HCV positive tests or genetic material
(ribonucleic acid) testing positive results.
16. Patient with a history of hypersensitivity reaction to inhaled anticholinergic drugs,
sympathomimetic amines, inhaled medication or any component thereof.
17. Patient with known narrow-angle glaucoma, symptomatic bladder neck obstruction,
acute urinary retention, or patients with symptomatic non-stable prostatic hypertrophy.
Explanatory note: Patients with well-controlled, stable, asymptomatic benign
prostatic hypertrophy are not excluded.
18. History of malignancy of any organ system (including lung cancer), treated or
untreated, within the past 5 years other than basal or squamous cell skin cancer.
Explanatory note: Patients are excluded whether or not there is evidence of
local recurrence or metastases.
19. Any other serious or uncontrolled physical or mental dysfunction.
Explanatory note: as judged by the Investigator, the dysfunction could place the
patient at a higher risk as a result of his/her participation in the study, or
confound the results of the study, or would be likely to prevent the patient from
complying with the requirements of the study or completing the study
20. Patients with a history (within 2 years prior to Visit 1 (screening) of drug and/or
alcohol abuse that may prevent study compliance based on the Investigator judgment.
21. Patients unlikely to be cooperative or cannot comply with the study procedures
Explanatory note: patients who may have difficulties following the treatment,
completing the patient diary, or attending the clinic at the required times, or
unable to properly use a DPI or pressured metered dose inhaler device, or
performing spirometry measurements.
22. Patients treated with any investigational drug within 30 days (or 6 half-lives,
whichever is longer) prior to screening.
23. 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.
24. Patients unable to give consent, or patients of consenting age but under guardianship,
or vulnerable patients.
25. Any other conditions that, in the Investigator’s opinion, might have indicated the
patient to be unsuitable for the study.
The Estimated Number of Participants
-
Taiwan
90 participants
-
Global
1515 participants
