Clinical Trials List
Protocol NumberCNVA237A2314
2012-06-15 - 2013-02-28
Phase III
Terminated7
ICD-10J44.9
Chronic obstructive pulmonary disease, unspecified
ICD-9496
Chronic airways obstruction, not elsewhere classified
A 12-week treatment, randomized, blinded, double-dummy, parallel-group study to assess the efficacy, safety, and tolerability of NVA237 (50 μg o.d.) compared to tiotropium (18 μg o.d.) in patients with chronic obstructive pulmonary disease (COPD)
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
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Sponsor
NOVARTIS
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Trial scale
Multi-Regional Multi-Center
-
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
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 歐亭芸 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chen Chia-Hung Division of Thoracic Medicine
- 梁信杰 Division of Thoracic Medicine
- 余養豪 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
COPD
Objectives
The purpose of this study is to allow a blinded comparison of the spirometric and symptomatic efficacy of NVA237 50μg o.d. with that of tiotropium 18μg o.d. and to compare the tolerability /
safety profile of the two compounds in patients with moderate to severe COPD
Test Drug
NVA237
Active Ingredient
NVA237
Dosage Form
Dosage
50
Endpoints
Efficacy assessments:
• Spirometry measurements (FEV1, FVC, IC)
• SGRQ
• BDI/TDI
• Rescue medication
• Patient reported symptoms
• COPD exacerbation
Safety assessments:
• Physical examination
• Vital signs
• Height and weight
• Laboratory evaluations: standard hematology, clinical chemistry, and
urinalysis panels
• Electrocardiogram (ECG)
• Pregnancy and assessments of fertility
• Spirometry measurements (FEV1, FVC, IC)
• SGRQ
• BDI/TDI
• Rescue medication
• Patient reported symptoms
• COPD exacerbation
Safety assessments:
• Physical examination
• Vital signs
• Height and weight
• Laboratory evaluations: standard hematology, clinical chemistry, and
urinalysis panels
• Electrocardiogram (ECG)
• Pregnancy and assessments of fertility
Inclution Criteria
Inclusion criteria
1. Male and female adults aged ≥40 years, who have signed an Informed Consent Form before any assessment is performed. (Patients participating in the pharmacogenetic sub-study must give additional written consent).
2. Patients with moderate to severe stable COPD (Stage II or Stage III)
according to the current GOLD Guidelines (GOLD 2010).
3. Patients with a post-bronchodilator FEV1 ≥ 30% and < 80% of the predicted normal, and a post-bronchodilator FEV1/FVC < 0.70 at screening (Postbronchodilator refers to 45 minutes after inhalation of 84 µg ipratropium (or equivalent dose)).
4. Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack/day x 10 yrs, or ½ pack/day x 20 yrs).
5. Symptomatic patients, according to daily electronic diary data between Visit 2 (Day -14) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3.
1. Male and female adults aged ≥40 years, who have signed an Informed Consent Form before any assessment is performed. (Patients participating in the pharmacogenetic sub-study must give additional written consent).
2. Patients with moderate to severe stable COPD (Stage II or Stage III)
according to the current GOLD Guidelines (GOLD 2010).
3. Patients with a post-bronchodilator FEV1 ≥ 30% and < 80% of the predicted normal, and a post-bronchodilator FEV1/FVC < 0.70 at screening (Postbronchodilator refers to 45 minutes after inhalation of 84 µg ipratropium (or equivalent dose)).
4. Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack/day x 10 yrs, or ½ pack/day x 20 yrs).
5. Symptomatic patients, according to daily electronic diary data between Visit 2 (Day -14) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3.
Exclusion Criteria
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 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 (have had surgical bilateral oophorectomy with or
without hysterectomy) or tubal ligation at least six weeks before taking
study treatment. In case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow up
hormone level assessment
• Male sterilization (at least 6 m 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
• Placement of an intrauterine device (IUD) or intrauterine system (IUS)
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.
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 QTc > 450 msec (Fridericia method) for both males and females at screening (Visit 1) or baseline (Visit 3).
5. Patients who have a clinically significant ECG abnormality at screening (Visit
1).
6. Patients who in the judgment of the investigator, would be at potential risk if
enrolled into the study.
7. Patients who, in the judgment of the investigator, or the responsible Novartis
personnel, have a clinically relevant laboratory abnormality or a clinically
significant condition before Visit 1, such as (but not limited to):
• 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
• Patients with paroxysmal atrial fibrillation or those patients with atrial
fibrillation maintained on a rhythm control strategy 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., beta
blocker, calcium channel blocker, pacemaker placement, digoxin, or
ablation therapy) for at least 6 months, with no plans for cardioversion
may be considered for inclusion. In such patients, atrial fibrillation must
be present at Baseline (Visit 3) and Screening (Visit 1) visits, with a
resting ventricular rate < 100/min. At Visit 1, atrial fibrillation must be
confirmed by central reading
8. 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
9. History of hypersensitivity to any of the study drugs or to drugs of similar
chemical classes.
10. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
11. Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. (BPH patients who are stable on treatment can be considered).
12. Patients who have not achieved an acceptable spirometry result at screening (Visit 2) in accordance with ATS/ERS criteria for acceptability and repeatability.
13. Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to screening (Visit 1).
14. Patients who develop a COPD exacerbation between screening (Visit 1) and treatment (Visit 3) 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 (Visit 1) and treatment (Visit 3) will not be eligible, but will be permitted to be rescreened 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 or onset of symptoms prior to age 40 years.
19. Patients with a blood eosinophil count > 600/mm3 during screening (Visit 2).
20. Patients with allergic rhinitis who use a 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, pulmonary hypertension).
22. Patients with clinically significant bronchiectasis.
23. Patients with a diagnosis of α-1 anti-trypsin deficiency.
24. Patients with active pulmonary tuberculosis, unless confirmed by imaging to be no longer active.
25. Patients with pulmonary lobectomy or lung volume reduction surgery or lung transplantation.
26. Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study. (Maintenance program is permitted.)
27. Patients receiving any medications in the classes listed in Table 5-1
28.Patients receiving any COPD related medications in the classes specified in Table 5-2 must undergo the required washout period prior to screening (Visit 2) and follow the adjustment to treatment program.
29. 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.
30. Use of other investigational drugs within 5 half-lives of enrollment, or within 30
days, whichever is longer.
31. Patients unable to use an electronic patient diary.
32. Patients unable to use a dry powder inhaler device, metered dose inhaler, or a pressurized MDI (rescue medication) or comply with the study regimen. Spacer devices are not permitted.
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 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 (have had surgical bilateral oophorectomy with or
without hysterectomy) or tubal ligation at least six weeks before taking
study treatment. In case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow up
hormone level assessment
• Male sterilization (at least 6 m 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
• Placement of an intrauterine device (IUD) or intrauterine system (IUS)
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.
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 QTc > 450 msec (Fridericia method) for both males and females at screening (Visit 1) or baseline (Visit 3).
5. Patients who have a clinically significant ECG abnormality at screening (Visit
1).
6. Patients who in the judgment of the investigator, would be at potential risk if
enrolled into the study.
7. Patients who, in the judgment of the investigator, or the responsible Novartis
personnel, have a clinically relevant laboratory abnormality or a clinically
significant condition before Visit 1, such as (but not limited to):
• 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
• Patients with paroxysmal atrial fibrillation or those patients with atrial
fibrillation maintained on a rhythm control strategy 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., beta
blocker, calcium channel blocker, pacemaker placement, digoxin, or
ablation therapy) for at least 6 months, with no plans for cardioversion
may be considered for inclusion. In such patients, atrial fibrillation must
be present at Baseline (Visit 3) and Screening (Visit 1) visits, with a
resting ventricular rate < 100/min. At Visit 1, atrial fibrillation must be
confirmed by central reading
8. 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
9. History of hypersensitivity to any of the study drugs or to drugs of similar
chemical classes.
10. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
11. Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. (BPH patients who are stable on treatment can be considered).
12. Patients who have not achieved an acceptable spirometry result at screening (Visit 2) in accordance with ATS/ERS criteria for acceptability and repeatability.
13. Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to screening (Visit 1).
14. Patients who develop a COPD exacerbation between screening (Visit 1) and treatment (Visit 3) 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 (Visit 1) and treatment (Visit 3) will not be eligible, but will be permitted to be rescreened 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 or onset of symptoms prior to age 40 years.
19. Patients with a blood eosinophil count > 600/mm3 during screening (Visit 2).
20. Patients with allergic rhinitis who use a 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, pulmonary hypertension).
22. Patients with clinically significant bronchiectasis.
23. Patients with a diagnosis of α-1 anti-trypsin deficiency.
24. Patients with active pulmonary tuberculosis, unless confirmed by imaging to be no longer active.
25. Patients with pulmonary lobectomy or lung volume reduction surgery or lung transplantation.
26. Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study. (Maintenance program is permitted.)
27. Patients receiving any medications in the classes listed in Table 5-1
28.Patients receiving any COPD related medications in the classes specified in Table 5-2 must undergo the required washout period prior to screening (Visit 2) and follow the adjustment to treatment program.
29. 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.
30. Use of other investigational drugs within 5 half-lives of enrollment, or within 30
days, whichever is longer.
31. Patients unable to use an electronic patient diary.
32. Patients unable to use a dry powder inhaler device, metered dose inhaler, or a pressurized MDI (rescue medication) or comply with the study regimen. Spacer devices are not permitted.
The Estimated Number of Participants
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Taiwan
40 participants
-
Global
660 participants
