Clinical Trials List
Protocol NumberCNVA237A2311
2013-03-01 - 2014-12-31
Phase III
Terminated9
ICD-10J44.9
Chronic obstructive pulmonary disease, unspecified
ICD-9496
Chronic airways obstruction, not elsewhere classified
A 26-week multi-center randomized double-blind study to compare efficacy and safety of NVA237 versus placebo as an add-on to maintenance therapy with fixed-dose combination salmeterol/ fluticasone propionate in COPD patients with moderate to severe airflow limitation.
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 周昆達 Division of Thoracic Medicine
- Kang-Cheng Su Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 游騰仁 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 張晃智 Division of Thoracic Medicine
- 黃國棟 Division of Thoracic Medicine
- 秦建弘 Division of Thoracic Medicine
- 梁深怡 Division of Thoracic Medicine
- 蘇茂昌 Division of Thoracic Medicine
- 陳永哲 Division of Thoracic Medicine
- 吳沼漧 Division of Thoracic Medicine
- 劉世豐 Division of Thoracic Medicine
- 陳泓丞 Division of Thoracic Medicine
- 方文豐 Division of Thoracic Medicine
- Chia-Cheng Tseng Division of Thoracic Medicine
- 王逸熙 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
Co-Principal Investigator
- 陳鴻仁 Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
COPD
Objectives
Primary objective:
To demonstrate the superiority of inhaled NVA237 (50 μg once daily [od] via SDDPI) compared with placebo when added on to a fixed-dose combination of salmeterol/fluticasone propionate (50/500 μg bid via MDDPI), in terms of trough FEV1 after 12 weeks of treatment in the study population.
Test Drug
NVA237
Active Ingredient
NVA237
Dosage Form
capsule
Dosage
50
Endpoints
All efficacy assessments:
Spirometry assessments (FEV1, FEV1 area under the curve [AUC]5 min-4 h, peak FEV1, FVC, trough inspiratory capacity (resting)
SGRQ-C
CAT
6-minute walk test
Baseline Dyspnea Index and Transition Dyspnea Index (BDI/TDI)
Patient-reported daily symptoms from the electronic patient diary (eDiary)
Patient-reported morning COPD symptoms (Morning Symptoms Diary)
Patient-reported physical activity in daily life (PROactive questionnaire)
Rescue medication use (eDiary)
Frequency of moderate and severe exacerbations
Time to first moderate to severe COPD exacerbation
Other assessments: The safety assessments include the following:
Adverse events (including COPD exacerbations)
Physical examination
Vital signs
Body weight
Laboratory evaluations
Electrocardiogram
Spirometry assessments (FEV1, FEV1 area under the curve [AUC]5 min-4 h, peak FEV1, FVC, trough inspiratory capacity (resting)
SGRQ-C
CAT
6-minute walk test
Baseline Dyspnea Index and Transition Dyspnea Index (BDI/TDI)
Patient-reported daily symptoms from the electronic patient diary (eDiary)
Patient-reported morning COPD symptoms (Morning Symptoms Diary)
Patient-reported physical activity in daily life (PROactive questionnaire)
Rescue medication use (eDiary)
Frequency of moderate and severe exacerbations
Time to first moderate to severe COPD exacerbation
Other assessments: The safety assessments include the following:
Adverse events (including COPD exacerbations)
Physical examination
Vital signs
Body weight
Laboratory evaluations
Electrocardiogram
Inclution Criteria
Inclusion criteria:
1. Male and female adults age ≥40 years.
2. Patients who have signed the study informed consent form prior to initiation of any study-related procedure.
3. Current or ex-smokers who have a smoking history of at least 10 pack years (e.g., 10 pack
years = 1 pack/day × 10 years, ½ pack/day × 20 years, etc.).
4. COPD patients with moderate to severe airflow limitation (spirometric classification:
GOLD 2 or 3) at Visit 2, i.e.,
• Post-bronchodilator FEV1 ≥30% and <60% of the predicted normal, and
• Post-bronchodilator FEV1/forced vital capacity (FVC) <0.70. (Post-bronchodilator refers to 1 hour after sequential inhalation of 84 µg ipratropium bromide and 400 µg salbutamol.)
5. Patients on maintenance treatment with fixed-dose combination of inhaled salmeterol and fluticasone propionate (50/500 µg) bid delivered via a proprietary MDDPI device for at
least 30 days prior to the screening visit (Visit 1).
6. Patients in category Gold B or D with a CAT total score ≥10 at screening (Visit 1) and
before randomization (Visit 3).
7. Patients with a history of at least 1 moderate or severe COPD exacerbation within the
previous year.
1. Male and female adults age ≥40 years.
2. Patients who have signed the study informed consent form prior to initiation of any study-related procedure.
3. Current or ex-smokers who have a smoking history of at least 10 pack years (e.g., 10 pack
years = 1 pack/day × 10 years, ½ pack/day × 20 years, etc.).
4. COPD patients with moderate to severe airflow limitation (spirometric classification:
GOLD 2 or 3) at Visit 2, i.e.,
• Post-bronchodilator FEV1 ≥30% and <60% of the predicted normal, and
• Post-bronchodilator FEV1/forced vital capacity (FVC) <0.70. (Post-bronchodilator refers to 1 hour after sequential inhalation of 84 µg ipratropium bromide and 400 µg salbutamol.)
5. Patients on maintenance treatment with fixed-dose combination of inhaled salmeterol and fluticasone propionate (50/500 µg) bid delivered via a proprietary MDDPI device for at
least 30 days prior to the screening visit (Visit 1).
6. Patients in category Gold B or D with a CAT total score ≥10 at screening (Visit 1) and
before randomization (Visit 3).
7. Patients with a history of at least 1 moderate or severe COPD exacerbation within the
previous year.
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 β-hCG 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.
3. Patients with type 1 or uncontrolled type 2 diabetes mellitus (as judged by the investigator).
4. Patients with a history of long QT syndrome or whose QTc measured at the beginning of the run-in period (using Fridericia’s formula) is prolonged (>450 ms).
5. Patients who have a clinically significant electrocardiogram abnormality at the beginning of the run-in period.
6. Patients who have a clinically significant laboratory abnormality at the beginning of the run-in period.
7. Patients with a body mass index of more than 40 kg/m2
8. Patients who have clinically significant renal, cardiovascular (such as, but not limited to, unstable ischemic heart disease, New York Heart Association Class III/IV left ventricular failure, myocardial infarction, or arrhythmia), neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment.
9. Patients with paroxysmal (e.g., intermittent) atrial fibrillation/flutter are excluded.
10. 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 β2-agonists
ICS
sympathomimetic amines
lactose or any of the other excipients of the study medication.
11. 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.
12. Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia, bladder neck obstruction, or moderate to severe renal impairment or urinary retention. (Benign prostatic hyperplasia patients who are stable on treatment can be considered.)
13. Patients with evidence (upon visual inspection) of oropharyngeal candidiasis at baseline with or without treatment.
14. Patients who have not achieved an acceptable spirometry result at the beginning of the run-in period in accordance with American Thoracic Society/European Respiratory Society criteria for acceptability and repeatability.
15. Patients who have had a COPD exacerbation that required treatment with antibiotics or oral corticosteroids or hospitalization in the 6 weeks prior to screening.
16. Patients who have had a respiratory tract infection within 4 weeks prior to screening.
17. Patients requiring long-term oxygen therapy prescribed for >12 hours per day.
18. Patients with any history of asthma or onset of respiratory symptoms prior to the age of 40 years.
19. Patients with a blood eosinophil count >600/mm3 at the beginning of the run-in period.
20. Patients with allergic rhinitis who use an H1 antagonist or intra-nasal corticosteroids intermittently. (Treatment with a stable dose or regimen is permitted.)
21. Patients with concomitant pulmonary disease (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, active tuberculosis, or pulmonary hypertension), clinically significant bronchiectasis, or history of pulmonary lobectomy, lung volume reduction surgery, or lung transplantation.
22. Patients with a diagnosis of α-1 anti-trypsin deficiency.
23. Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study. (Maintenance program is permitted.)
24. Patients receiving any medications in the classes listed in Table 5-1.
25. Patients receiving any COPD-related medications in the classes specified in Table 5-2 unless they undergo the required washout period prior to the beginning of the run-in period.
26. Patients receiving medications in the classes listed in Table 5-3 should be excluded unless the medication has been stabilized for the specified period and the stated conditions have been met.
27. Use of other investigational drugs (approved or unapproved) at the time of screening or within 30 days or 5 half-lives of Visit 1, whichever is longer.
28. Patients unable to use the electronic patient-reported outcome device.
29. Patients unable to use a dry powder inhaler device or a pressurized metered dose inhaler (rescue medication) or to comply with the study regimen. Spacer devices are not permitted.
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.
3. Patients with type 1 or uncontrolled type 2 diabetes mellitus (as judged by the investigator).
4. Patients with a history of long QT syndrome or whose QTc measured at the beginning of the run-in period (using Fridericia’s formula) is prolonged (>450 ms).
5. Patients who have a clinically significant electrocardiogram abnormality at the beginning of the run-in period.
6. Patients who have a clinically significant laboratory abnormality at the beginning of the run-in period.
7. Patients with a body mass index of more than 40 kg/m2
8. Patients who have clinically significant renal, cardiovascular (such as, but not limited to, unstable ischemic heart disease, New York Heart Association Class III/IV left ventricular failure, myocardial infarction, or arrhythmia), neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment.
9. Patients with paroxysmal (e.g., intermittent) atrial fibrillation/flutter are excluded.
10. 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 β2-agonists
ICS
sympathomimetic amines
lactose or any of the other excipients of the study medication.
11. 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.
12. Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia, bladder neck obstruction, or moderate to severe renal impairment or urinary retention. (Benign prostatic hyperplasia patients who are stable on treatment can be considered.)
13. Patients with evidence (upon visual inspection) of oropharyngeal candidiasis at baseline with or without treatment.
14. Patients who have not achieved an acceptable spirometry result at the beginning of the run-in period in accordance with American Thoracic Society/European Respiratory Society criteria for acceptability and repeatability.
15. Patients who have had a COPD exacerbation that required treatment with antibiotics or oral corticosteroids or hospitalization in the 6 weeks prior to screening.
16. Patients who have had a respiratory tract infection within 4 weeks prior to screening.
17. Patients requiring long-term oxygen therapy prescribed for >12 hours per day.
18. Patients with any history of asthma or onset of respiratory symptoms prior to the age of 40 years.
19. Patients with a blood eosinophil count >600/mm3 at the beginning of the run-in period.
20. Patients with allergic rhinitis who use an H1 antagonist or intra-nasal corticosteroids intermittently. (Treatment with a stable dose or regimen is permitted.)
21. Patients with concomitant pulmonary disease (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, active tuberculosis, or pulmonary hypertension), clinically significant bronchiectasis, or history of pulmonary lobectomy, lung volume reduction surgery, or lung transplantation.
22. Patients with a diagnosis of α-1 anti-trypsin deficiency.
23. Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study. (Maintenance program is permitted.)
24. Patients receiving any medications in the classes listed in Table 5-1.
25. Patients receiving any COPD-related medications in the classes specified in Table 5-2 unless they undergo the required washout period prior to the beginning of the run-in period.
26. Patients receiving medications in the classes listed in Table 5-3 should be excluded unless the medication has been stabilized for the specified period and the stated conditions have been met.
27. Use of other investigational drugs (approved or unapproved) at the time of screening or within 30 days or 5 half-lives of Visit 1, whichever is longer.
28. Patients unable to use the electronic patient-reported outcome device.
29. Patients unable to use a dry powder inhaler device or a pressurized metered dose inhaler (rescue medication) or to comply with the study regimen. Spacer devices are not permitted.
The Estimated Number of Participants
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Taiwan
67 participants
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Global
1120 participants
