Clinical Trials List
Protocol NumberCQVA149A2318
2013-09-10 - 2015-10-31
Phase III
Terminated7
Study ended1
ICD-10J44.9
Chronic obstructive pulmonary disease, unspecified
ICD-9496
Chronic airways obstruction, not elsewhere classified
A 52-week treatment, multi-center, randomized, doubleblind, double dummy, parallel-group, active controlled study to compare the effect of QVA149 (indacaterol maleate / glycopyrronium bromide) with salmeterol/fluticasone on the rate of exacerbations in subjects with moderate to very severe COPD
-
Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ping-Hung Kuo Division of Thoracic Medicine
- Shih-Chi Ku Division of Thoracic Medicine
- 郭律成 Division of Thoracic Medicine
- HAO-CHIEN WANG Division of Thoracic Medicine
- 阮聖元 Division of Thoracic Medicine
- 鄭之勛 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Kang-Cheng Su Division of Thoracic Medicine
- 周昆達 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 覃俊士 Division of Thoracic Medicine
- Wei- Chang Huang Division of Thoracic Medicine
- 王振宇 Division of Thoracic Medicine
- Ming -Cheng Chan Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Cheng-Hung Lee Division of Thoracic Medicine
- 陳炯睿 Division of Thoracic Medicine
- Chih-Ying Ou Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chih-Ching Yen Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
- Wei-Chun Chen Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- Te-Chun Shen Division of Thoracic Medicine
- 梁信杰 Division of Thoracic Medicine
- Shuo-Chueh Chen Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
5 Study ended
Condition/Disease
moderate to very severe COPD
Objectives
Primary Objective:
To demonstrate that QVA149 (110/50 µg o.d.) is at least noninferior to salmeterol/fluticasone (50/500 µg b.i.d.) in terms of rate
of COPD exacerbations (mild/moderate/severe) during 52 weeks of
treatment.
Test Drug
QVA149
Active Ingredient
[QAB149 (indacaterol maleate)/ NVA237 (glycopyrronium bromide)]
Dosage Form
capsule
Dosage
110/50
Endpoints
Efficacy assessments:
• COPD exacerbations
• Spirometry
• SGRQ-C
• Rescue medication use
• CAT
• EXACT PRO
• Resource utilization
Safety assessments:
• ECG
• Laboratory tests
• Vital signs
• Adverse Events
• 24-hour urine cortisol (sub-set of patients)
• Oral fungal infections
• COPD exacerbations
• Spirometry
• SGRQ-C
• Rescue medication use
• CAT
• EXACT PRO
• Resource utilization
Safety assessments:
• ECG
• Laboratory tests
• Vital signs
• Adverse Events
• 24-hour urine cortisol (sub-set of patients)
• Oral fungal infections
Inclution Criteria
1. Written informed consent must be obtained before any
assessment is performed.
2. Male or female adults aged ≥40 years.
3. Patients with stable COPD according to the current GOLD
strategy (GOLD 2011).
4. Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day
for 10 years, or 10 cigarettes a day for 20 years).
5. Patients with a post-bronchodilator FEV1 ≥25 and < 60% of the
predicted normal value, and post-bronchodilator FEV1/FVC <
0.70 at Visit 101 (day -28).
(Post refers to 1 h after sequential inhalation of 84 µg (or
equivalent dose) of ipratropium bromide and 400 µg of
salbutamol).
6. A documented history of at least 1 COPD exacerbation in the
previous 12 months that required treatment with systemic
glucocorticosteroids and/or antibiotics.
7. Patients taking stable COPD medication (at least 60 days) prior
to Visit 101.
8. Patients with an mMRC grade of at least 2 at Visit 101 (day -
28).
assessment is performed.
2. Male or female adults aged ≥40 years.
3. Patients with stable COPD according to the current GOLD
strategy (GOLD 2011).
4. Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day
for 10 years, or 10 cigarettes a day for 20 years).
5. Patients with a post-bronchodilator FEV1 ≥25 and < 60% of the
predicted normal value, and post-bronchodilator FEV1/FVC <
0.70 at Visit 101 (day -28).
(Post refers to 1 h after sequential inhalation of 84 µg (or
equivalent dose) of ipratropium bromide and 400 µg of
salbutamol).
6. A documented history of at least 1 COPD exacerbation in the
previous 12 months that required treatment with systemic
glucocorticosteroids and/or antibiotics.
7. Patients taking stable COPD medication (at least 60 days) prior
to Visit 101.
8. Patients with an mMRC grade of at least 2 at Visit 101 (day -
28).
Exclusion Criteria
1. Pregnant or nursing (lactating) women, where pregnancy is
defined as the state of a female after conception and until the
termination of gestation, confirmed by a positive hCG (human
Chorionic Gonadotropin) laboratory test.
2. Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant, unless they are
using effective methods of contraception during dosing of study
treatment. Effective contraception methods include:
• Total abstinence when this is in line with the preferred and
usual lifestyle of the subject (periodic abstinence (e.g.,
calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of
contraception).
• Female sterilization defined as surgical hysterectomy,
bilateral oophorectomy, or tubal ligation at least six weeks
before taking the study treatment (Single oophorectomy
does not meet the definition of female sterilization).
• Male sterilization (at least 6 months prior to screening). For
female subjects on the study, the vasectomized male partner
should be the sole partner for that subject.
• Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository.
• Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that
have comparable efficacy (failure rate <1%), for example
hormone vaginal ring or transdermal hormone
contraception. In case of use of oral contraception women
should have been stable on the same pill for a minimum of 3
months before taking study treatment.
• Placement of an intrauterine device (IUD) or intrauterine
system (IUS).
Women are considered post-menopausal and not of child
bearing potential if they have had 12 months of natural
(spontaneous) amenorrhea with an appropriate clinical
profile (e.g. age appropriate, history of vasomotor
symptoms) or have had surgical bilateral oophorectomy
(with or without hysterectomy) or tubal ligation at least six
weeks ago. In the case of oophorectomy alone, only when
the reproductive status of the woman has been confirmed by
follow up hormone level assessment is she considered not of
child bearing potential.
3. Patients with Type I or uncontrolled Type II diabetes.
4. Patients with a history of long QT syndrome or whose QTc
measured at Visit 101 (Fridericia method) is prolonged (>450 ms
for males and females) and confirmed by a central assessor.
These patients should not be re-screened.
5. Patients who have a clinically significant ECG abnormality at
Visit 101 or Visit 201. (These patients should not be rescreened)
6. Patients who have a clinically significant laboratory abnormality
at Visit 101.
7. Patients who have clinically significant renal, cardiovascular
(such as but not limited to unstable ischemic heart disease,
NYHA Class III/IV left ventricular failure, myocardial
infarction), arrhythmia (see below for patients with atrial
fibrillation), neurological, endocrine, immunological,
psychiatric, gastrointestinal, hepatic, or hematological
abnormalities which could interfere with the assessment of the
efficacy and safety of the study treatment.
8. Patients with paroxysmal (e.g. intermittent) atrial fibrillation are
excluded. Patients with persistent atrial fibrillation as defined by
continuous atrial fibrillation for at least 6 months and controlled
with a rate control strategy (i.e., selective beta blocker, calcium
channel blocker, pacemaker placement, digoxin or ablation
therapy) for at least 6 months may be considered for inclusion.
In such patients, atrial fibrillation must be present at Visit 101
and Visit 102 with a resting ventricular rate < 100/min. At Visit 101 the atrial fibrillation must be confirmed by central reading.
9. Patients contraindicated for treatment with, or having a history
of reactions/ hypersensitivity to any of the following inhaled
drugs, drugs of a similar class or any component thereof:
• anticholinergic agents
• long and short acting beta-2 agonists
• sympathomimetic amines
• lactose or any of the other excipients of trial medication
10. Patients with a history of malignancy of any organ system,
treated or untreated, within the past 5 years whether or not there
is evidence of local recurrence or metastases, with the exception
of localized basal cell carcinoma of the skin.
11. Patients with narrow-angle glaucoma, symptomatic benign
prostatic hyperplasia or bladder-neck obstruction or moderate to
severe renal impairment or urinary retention. Benign Prostatic
Hyperplasia (BPH) patients who are stable on treatment can be
considered.
12. Patients who have not achieved an acceptable spirometry results
at Visit 101 in accordance with American Thoracic Society
(ATS)/European Respiratory Society (ERS) criteria for
acceptability (one retest may be performed for patients that don’t
meet the acceptability criteria).
13. Patients who have had a COPD exacerbation that required
treatment with antibiotics and/or systemic corticosteroids and/or
hospitalization in the 6 weeks prior to Visit 1.
14. Patients who develop a COPD exacerbation between screening
(Visit 1) and treatment (Visit 201) will not be eligible but will be
permitted to be re-screened after a minimum of 6 weeks after the
resolution of the COPD exacerbation.
15. Patients who have had a respiratory tract infection within 4
weeks prior to screening Visit 1.
16. Patients who develop a respiratory tract infection between
screening and prior to treatment will not be eligible, but will be
permitted to be re-screened 4 weeks after the resolution of the
respiratory tract infection.
17. Patients requiring long term oxygen therapy prescribed for >12
hours per day.
18. Patients with any history of asthma.
19. Patients with an onset of respiratory symptoms, including a
COPD diagnosis prior to age 40 years.
20. Patients with a blood eosinophil count > 600/mm3
at Visit 101.
21. Patients with allergic rhinitis who use a H1 antagonist or intra nasal corticosteroids intermittently (treatment with a stable dose
or regimen is permitted).
22. Patients with concomitant pulmonary disease (e.g. lung fibrosis,
sarcoidosis, interstitial lung disease, pulmonary hypertension).
23. Patients with clinically significant bronchiectasis.
24. Patients with a diagnosis of α-1 anti-trypsin deficiency.
25. Patients with active pulmonary tuberculosis, unless confirmed by
imaging to be no longer active.
26. Patients with pulmonary lobectomy or lung volume reduction
surgery or lung transplantation.
27. Patients participating in or planning to participate in the active
phase of a supervised pulmonary rehabilitation program during
the study. (Maintenance program is permitted.)
28. Patients receiving any medications in the classes listed in Table
5-1.
29. Patients receiving any COPD related medications in the classes
specified in Table 5-2 must undergo the required washout period
prior to Visit 101 and follow the adjustment to treatment
program.
30. Patients receiving medications in the classes listed in Table 5-3
should be excluded unless the medication has been stable for the
specified period and the stated conditions have been met.
31. Use of other investigational drugs/devices (approved or
unapproved) at the time of enrollment, or within 30 days or 5
half-lives of Visit 1, whichever is longer.
32. Patients unable to use an electronic patient diary and EXACT
pro diary.
33. Patients unable to use dry powder inhaler device. Metered Dose
Inhaler (MDI) or a pressurized MDI (rescue medication) or
comply with the study regimen.
defined as the state of a female after conception and until the
termination of gestation, confirmed by a positive hCG (human
Chorionic Gonadotropin) laboratory test.
2. Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant, unless they are
using effective methods of contraception during dosing of study
treatment. Effective contraception methods include:
• Total abstinence when this is in line with the preferred and
usual lifestyle of the subject (periodic abstinence (e.g.,
calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of
contraception).
• Female sterilization defined as surgical hysterectomy,
bilateral oophorectomy, or tubal ligation at least six weeks
before taking the study treatment (Single oophorectomy
does not meet the definition of female sterilization).
• Male sterilization (at least 6 months prior to screening). For
female subjects on the study, the vasectomized male partner
should be the sole partner for that subject.
• Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository.
• Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that
have comparable efficacy (failure rate <1%), for example
hormone vaginal ring or transdermal hormone
contraception. In case of use of oral contraception women
should have been stable on the same pill for a minimum of 3
months before taking study treatment.
• Placement of an intrauterine device (IUD) or intrauterine
system (IUS).
Women are considered post-menopausal and not of child
bearing potential if they have had 12 months of natural
(spontaneous) amenorrhea with an appropriate clinical
profile (e.g. age appropriate, history of vasomotor
symptoms) or have had surgical bilateral oophorectomy
(with or without hysterectomy) or tubal ligation at least six
weeks ago. In the case of oophorectomy alone, only when
the reproductive status of the woman has been confirmed by
follow up hormone level assessment is she considered not of
child bearing potential.
3. Patients with Type I or uncontrolled Type II diabetes.
4. Patients with a history of long QT syndrome or whose QTc
measured at Visit 101 (Fridericia method) is prolonged (>450 ms
for males and females) and confirmed by a central assessor.
These patients should not be re-screened.
5. Patients who have a clinically significant ECG abnormality at
Visit 101 or Visit 201. (These patients should not be rescreened)
6. Patients who have a clinically significant laboratory abnormality
at Visit 101.
7. Patients who have clinically significant renal, cardiovascular
(such as but not limited to unstable ischemic heart disease,
NYHA Class III/IV left ventricular failure, myocardial
infarction), arrhythmia (see below for patients with atrial
fibrillation), neurological, endocrine, immunological,
psychiatric, gastrointestinal, hepatic, or hematological
abnormalities which could interfere with the assessment of the
efficacy and safety of the study treatment.
8. Patients with paroxysmal (e.g. intermittent) atrial fibrillation are
excluded. Patients with persistent atrial fibrillation as defined by
continuous atrial fibrillation for at least 6 months and controlled
with a rate control strategy (i.e., selective beta blocker, calcium
channel blocker, pacemaker placement, digoxin or ablation
therapy) for at least 6 months may be considered for inclusion.
In such patients, atrial fibrillation must be present at Visit 101
and Visit 102 with a resting ventricular rate < 100/min. At Visit 101 the atrial fibrillation must be confirmed by central reading.
9. Patients contraindicated for treatment with, or having a history
of reactions/ hypersensitivity to any of the following inhaled
drugs, drugs of a similar class or any component thereof:
• anticholinergic agents
• long and short acting beta-2 agonists
• sympathomimetic amines
• lactose or any of the other excipients of trial medication
10. Patients with a history of malignancy of any organ system,
treated or untreated, within the past 5 years whether or not there
is evidence of local recurrence or metastases, with the exception
of localized basal cell carcinoma of the skin.
11. Patients with narrow-angle glaucoma, symptomatic benign
prostatic hyperplasia or bladder-neck obstruction or moderate to
severe renal impairment or urinary retention. Benign Prostatic
Hyperplasia (BPH) patients who are stable on treatment can be
considered.
12. Patients who have not achieved an acceptable spirometry results
at Visit 101 in accordance with American Thoracic Society
(ATS)/European Respiratory Society (ERS) criteria for
acceptability (one retest may be performed for patients that don’t
meet the acceptability criteria).
13. Patients who have had a COPD exacerbation that required
treatment with antibiotics and/or systemic corticosteroids and/or
hospitalization in the 6 weeks prior to Visit 1.
14. Patients who develop a COPD exacerbation between screening
(Visit 1) and treatment (Visit 201) will not be eligible but will be
permitted to be re-screened after a minimum of 6 weeks after the
resolution of the COPD exacerbation.
15. Patients who have had a respiratory tract infection within 4
weeks prior to screening Visit 1.
16. Patients who develop a respiratory tract infection between
screening and prior to treatment will not be eligible, but will be
permitted to be re-screened 4 weeks after the resolution of the
respiratory tract infection.
17. Patients requiring long term oxygen therapy prescribed for >12
hours per day.
18. Patients with any history of asthma.
19. Patients with an onset of respiratory symptoms, including a
COPD diagnosis prior to age 40 years.
20. Patients with a blood eosinophil count > 600/mm3
at Visit 101.
21. Patients with allergic rhinitis who use a H1 antagonist or intra nasal corticosteroids intermittently (treatment with a stable dose
or regimen is permitted).
22. Patients with concomitant pulmonary disease (e.g. lung fibrosis,
sarcoidosis, interstitial lung disease, pulmonary hypertension).
23. Patients with clinically significant bronchiectasis.
24. Patients with a diagnosis of α-1 anti-trypsin deficiency.
25. Patients with active pulmonary tuberculosis, unless confirmed by
imaging to be no longer active.
26. Patients with pulmonary lobectomy or lung volume reduction
surgery or lung transplantation.
27. Patients participating in or planning to participate in the active
phase of a supervised pulmonary rehabilitation program during
the study. (Maintenance program is permitted.)
28. Patients receiving any medications in the classes listed in Table
5-1.
29. Patients receiving any COPD related medications in the classes
specified in Table 5-2 must undergo the required washout period
prior to Visit 101 and follow the adjustment to treatment
program.
30. Patients receiving medications in the classes listed in Table 5-3
should be excluded unless the medication has been stable for the
specified period and the stated conditions have been met.
31. Use of other investigational drugs/devices (approved or
unapproved) at the time of enrollment, or within 30 days or 5
half-lives of Visit 1, whichever is longer.
32. Patients unable to use an electronic patient diary and EXACT
pro diary.
33. Patients unable to use dry powder inhaler device. Metered Dose
Inhaler (MDI) or a pressurized MDI (rescue medication) or
comply with the study regimen.
The Estimated Number of Participants
-
Taiwan
25 participants
-
Global
3332 participants
