Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, NVA237
Brief summary
This is a 52-week, multi-center, randomized, open label, parallel group study to assess the long term safety and tolerability of once-daily NVA237, using tiotropium as an active control, in Japanese patients with moderate to severe chronic obstructive pulmonary disease (COPD) .
Interventions
DRUGNVA237
50µg capsules for inhalation, delivered via a single dose dry powder inhaler (Concept 1®)
DRUGTiotropium
18µg capsules for inhalation, delivered via HandiHaler®
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with moderate to severe stable COPD (Stage II or Stage III) according to the Gold Guideline 2008. * Current or ex-smokers who have a smoking history of at least 10 pack years. * Patients with a post-bronchodilator FEV1 ≥30% and \< 80% of the predicted normal, and postbronchodilator FEV1/FVC \< 0.7 at Visit 2 (day -7)
Exclusion criteria
* Pregnant women or nursing mothers or women of child-bearing potential not using an acceptable method of contraception * Patients requiring long term oxygen therapy * Patients who have had a lower respiratory tract infection within 6 weeks prior to Visit 1 * Patients with concomitant pulmonary disease * Patients with a history of asthma * Any patient with lung cancer or a history of lung cancer * Patients with a history of certain cardiovascular comorbid conditions * Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency * Patients in the active phase of a supervised pulmonary rehabilitation program * Patients contraindicated for tiotropium or ipratropium treatment or who have shown an untoward reaction to inhaled anticholinergic agents * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events, Serious Adverse Events or Death | 52 weeks | Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pre-dose FVC From Baseline | Weeks 12, 24, 36 and 52 | Pre-dose FVC is defined as the average of the measurements at 45 and 15 minutes pre-dose. |
| Time From Randomization Until the Start of the First Moderate or Severe COPD Exacerbation | 52 weeks | Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required. Participants who withdraw from the study and do not experience a moderate or severe exacerbation are censored at the date of withdrawal. Participants who complete the study and do not experience a moderate or severe exacerbation are censored at the completion visit date. |
| Number of Patients With Moderate or Severe COPD Exacerbations | 52 weeks | Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required. |
| Change in St. George Respiratory Questionnaire From Baseline | Weeks 12, 24, 36, 52 | SGRQ is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life. |
| Change in Pre-dose FEV1 From Baseline | Weeks 12, 24, 36 and 52 | Pre-dose FEV1 is defined as the average of the measurements at 45 and 15 minutes pre-dose. |
| Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | 52 weeks | Clinically notable hematology values were: hemoglobin - male \<11.5g/dL, female \<9.5 g/dL; hematocrit - male \<37%, female \<32%; white cell count - \<2800µL or \>16000µL; platelets - \<7.5 10\*4/µL or \>70.0 10\*4/µL |
| Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | 52 weeks | Clinically notable biochemistry values were: total protein - \<4.0 g/dL or \>9.5 g/dL; albumin \<2.5 g/dL; bilirubin (total) \>1.9 mg/dL; BUN \>27 mg/dL; creatinine \>1.99 mg/dL; AST \>3 x ULN U/L; ALT \>3 x ULN U/L; ALP \>3 x ULN U/L; y-GTP \>3 x ULN U/L; sodium \<125 mEq/L or \>160 mEq/L; potassium \<3.0 mEq/L or \>6.0 mEq/L; glucose \<51.0 mg/dL or \>180.0 mg/dL |
| Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | 52 weeks | Clinically notable vital sign values were: pulse rate - low, \<40 bpm or \<=50 bpm and decrease from baseline \>=15bpm; pulse rate high, \>130 bpm or \>=120bpm and increase from baseline \>=15 bpm. Systolic blood pressure - low, \<75 mmHg or \<=90 mmHg and decrease from baseline \>=20 mmHg; high, \>200 mmHg or \>=180 mmHg and increase from baseline \>=20 mmHg. Diastolic blood pressure - low, \<40 mmHg or \<=50 mmHg and decrease from baseline \>=15 mmHg; high, \>115 mmHg or \>=105 mmHg and increase from baseline \>=15 mmHg. |
| Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period | 52 weeks | Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms). |
| Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Over the Whole Treatment Period | 52 weeks | Patients recorded rescue medication use in a paper patient diary. If a patient required the use of salbutamol as rescue medication due to an increase in COPD symptoms, the number of inhalations (puffs) taken was recorded in the patient diary. |
Countries
Japan
Participant flow
Pre-assignment details
211 participants entered screening. 163 participants entered treatment.
Participants by arm
| Arm | Count |
|---|---|
| NVA237 50µg once daily | 123 |
| Tiotropium 18µg once daily | 40 |
| Total | 163 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 5 |
| Overall Study | Protocol deviation | 3 | 1 |
| Overall Study | Unsatisfactory therapeutic effect | 3 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | NVA237 | Tiotropium | Total |
|---|---|---|---|
| Age Continuous | 68.4 years STANDARD_DEVIATION 7.29 | 69.4 years STANDARD_DEVIATION 7.48 | 68.7 years STANDARD_DEVIATION 7.32 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 121 Participants | 38 Participants | 159 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 83 / 123 | 33 / 40 |
| serious Total, serious adverse events | 16 / 123 | 6 / 40 |
Outcome results
Primary
Number of Participants With Adverse Events, Serious Adverse Events or Death
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
Time frame: 52 weeks
Population: Safety population - all patients who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVA237 | Number of Participants With Adverse Events, Serious Adverse Events or Death | Adverse events | 102 participants |
| NVA237 | Number of Participants With Adverse Events, Serious Adverse Events or Death | Serious adverse events | 16 participants |
| NVA237 | Number of Participants With Adverse Events, Serious Adverse Events or Death | Death | 0 participants |
| Tiotropium | Number of Participants With Adverse Events, Serious Adverse Events or Death | Adverse events | 33 participants |
| Tiotropium | Number of Participants With Adverse Events, Serious Adverse Events or Death | Serious adverse events | 6 participants |
| Tiotropium | Number of Participants With Adverse Events, Serious Adverse Events or Death | Death | 0 participants |
Secondary
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Over the Whole Treatment Period
Patients recorded rescue medication use in a paper patient diary. If a patient required the use of salbutamol as rescue medication due to an increase in COPD symptoms, the number of inhalations (puffs) taken was recorded in the patient diary.
Time frame: 52 weeks
Population: Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Over the Whole Treatment Period | -0.16 change in puffs | Standard Deviation 1.039 |
| Tiotropium | Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Over the Whole Treatment Period | -0.27 change in puffs | Standard Deviation 0.859 |
Secondary
Change in Pre-dose FEV1 From Baseline
Pre-dose FEV1 is defined as the average of the measurements at 45 and 15 minutes pre-dose.
Time frame: Weeks 12, 24, 36 and 52
Population: Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug. Only participants with measurements at both baseline and the specified timepoint were included in the analysis for the specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change in Pre-dose FEV1 From Baseline | Week 12 | 0.101 liters | Standard Deviation 0.1455 |
| NVA237 | Change in Pre-dose FEV1 From Baseline | Week 24 | 0.094 liters | Standard Deviation 0.1614 |
| NVA237 | Change in Pre-dose FEV1 From Baseline | Week 36 (n = 106, 36) | 0.084 liters | Standard Deviation 0.1558 |
| NVA237 | Change in Pre-dose FEV1 From Baseline | Week 52 (n = 103, 33) | 0.068 liters | Standard Deviation 0.1829 |
| Tiotropium | Change in Pre-dose FEV1 From Baseline | Week 52 (n = 103, 33) | 0.127 liters | Standard Deviation 0.2566 |
| Tiotropium | Change in Pre-dose FEV1 From Baseline | Week 12 | 0.173 liters | Standard Deviation 0.1976 |
| Tiotropium | Change in Pre-dose FEV1 From Baseline | Week 36 (n = 106, 36) | 0.112 liters | Standard Deviation 0.22 |
| Tiotropium | Change in Pre-dose FEV1 From Baseline | Week 24 | 0.144 liters | Standard Deviation 0.1435 |
Secondary
Change in Pre-dose FVC From Baseline
Pre-dose FVC is defined as the average of the measurements at 45 and 15 minutes pre-dose.
Time frame: Weeks 12, 24, 36 and 52
Population: Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug. Only participants with measurements at both baseline and the specified timepoint were included in the analysis for the specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change in Pre-dose FVC From Baseline | Week 12 | 0.221 liters | Standard Deviation 0.3057 |
| NVA237 | Change in Pre-dose FVC From Baseline | Week 24 | 0.218 liters | Standard Deviation 0.2798 |
| NVA237 | Change in Pre-dose FVC From Baseline | Week 36 (n = 106, 36) | 0.208 liters | Standard Deviation 0.3204 |
| NVA237 | Change in Pre-dose FVC From Baseline | Week 52 (n = 103, 33) | 0.195 liters | Standard Deviation 0.3739 |
| Tiotropium | Change in Pre-dose FVC From Baseline | Week 52 (n = 103, 33) | 0.126 liters | Standard Deviation 0.2889 |
| Tiotropium | Change in Pre-dose FVC From Baseline | Week 12 | 0.220 liters | Standard Deviation 0.3029 |
| Tiotropium | Change in Pre-dose FVC From Baseline | Week 36 (n = 106, 36) | 0.146 liters | Standard Deviation 0.2547 |
| Tiotropium | Change in Pre-dose FVC From Baseline | Week 24 | 0.179 liters | Standard Deviation 0.2285 |
Secondary
Change in St. George Respiratory Questionnaire From Baseline
SGRQ is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life.
Time frame: Weeks 12, 24, 36, 52
Population: Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug. Only participants with measurements at both baseline and the specified timepoint were included in the analysis for the specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change in St. George Respiratory Questionnaire From Baseline | Week 12 | -2.57 score on a scale | Standard Deviation 8.506 |
| NVA237 | Change in St. George Respiratory Questionnaire From Baseline | Week 36 | -2.54 score on a scale | Standard Deviation 9.614 |
| NVA237 | Change in St. George Respiratory Questionnaire From Baseline | Week 52 | -2.68 score on a scale | Standard Deviation 10.505 |
| NVA237 | Change in St. George Respiratory Questionnaire From Baseline | Week 24 | -1.77 score on a scale | Standard Deviation 9.466 |
| Tiotropium | Change in St. George Respiratory Questionnaire From Baseline | Week 52 | 0.36 score on a scale | Standard Deviation 15.389 |
| Tiotropium | Change in St. George Respiratory Questionnaire From Baseline | Week 12 | -2.31 score on a scale | Standard Deviation 13.654 |
| Tiotropium | Change in St. George Respiratory Questionnaire From Baseline | Week 24 | -3.24 score on a scale | Standard Deviation 12.908 |
| Tiotropium | Change in St. George Respiratory Questionnaire From Baseline | Week 36 | -0.93 score on a scale | Standard Deviation 14.214 |
Secondary
Number of Patients With Moderate or Severe COPD Exacerbations
Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required.
Time frame: 52 weeks
Population: Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVA237 | Number of Patients With Moderate or Severe COPD Exacerbations | 1 exacerbation | 17 participants |
| NVA237 | Number of Patients With Moderate or Severe COPD Exacerbations | 3 exacerbations | 1 participants |
| NVA237 | Number of Patients With Moderate or Severe COPD Exacerbations | 2 exacerbations | 5 participants |
| NVA237 | Number of Patients With Moderate or Severe COPD Exacerbations | > = 4 exacerbations | 1 participants |
| NVA237 | Number of Patients With Moderate or Severe COPD Exacerbations | 0 exacerbations | 99 participants |
| Tiotropium | Number of Patients With Moderate or Severe COPD Exacerbations | > = 4 exacerbations | 1 participants |
| Tiotropium | Number of Patients With Moderate or Severe COPD Exacerbations | 0 exacerbations | 31 participants |
| Tiotropium | Number of Patients With Moderate or Severe COPD Exacerbations | 1 exacerbation | 5 participants |
| Tiotropium | Number of Patients With Moderate or Severe COPD Exacerbations | 2 exacerbations | 3 participants |
| Tiotropium | Number of Patients With Moderate or Severe COPD Exacerbations | 3 exacerbations | 0 participants |
Secondary
Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period
Clinically notable biochemistry values were: total protein - \<4.0 g/dL or \>9.5 g/dL; albumin \<2.5 g/dL; bilirubin (total) \>1.9 mg/dL; BUN \>27 mg/dL; creatinine \>1.99 mg/dL; AST \>3 x ULN U/L; ALT \>3 x ULN U/L; ALP \>3 x ULN U/L; y-GTP \>3 x ULN U/L; sodium \<125 mEq/L or \>160 mEq/L; potassium \<3.0 mEq/L or \>6.0 mEq/L; glucose \<51.0 mg/dL or \>180.0 mg/dL
Time frame: 52 weeks
Population: Safety population - all patients who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Potassium - <3.0 mEq/L | 1 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Total protein - <4.0 g/dL | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Total protein - >9.5 g/dL | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Albumin - <2.5 g/dL | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Bilirubin (total) - >1.9 mg/dL | 2 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | BUN - >27 mg/dL | 3 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Creatinine - >1.99 mg/dL | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | AST - >3 x ULN U/L | 1 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | ALT - >3 x ULN U/L | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | ALP - >3 x ULN U/L | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Y-GTP - >3 x ULN U/L | 5 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Sodium - <125 mEq/L | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Sodium - >160 mEq/L | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Potassium - >6.0 mEq/L | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Glucose - <51.0 mg/dL | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Glucose - >180.0 mg/dL | 11 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Glucose - >180.0 mg/dL | 3 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Potassium - <3.0 mEq/L | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | ALT - >3 x ULN U/L | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Total protein - <4.0 g/dL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Sodium - >160 mEq/L | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Total protein - >9.5 g/dL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | ALP - >3 x ULN U/L | 1 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Albumin - <2.5 g/dL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Glucose - <51.0 mg/dL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Bilirubin (total) - >1.9 mg/dL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Y-GTP - >3 x ULN U/L | 4 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | BUN - >27 mg/dL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Potassium - >6.0 mEq/L | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Creatinine - >1.99 mg/dL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Sodium - <125 mEq/L | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | AST - >3 x ULN U/L | 0 participants |
Secondary
Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period
Clinically notable hematology values were: hemoglobin - male \<11.5g/dL, female \<9.5 g/dL; hematocrit - male \<37%, female \<32%; white cell count - \<2800µL or \>16000µL; platelets - \<7.5 10\*4/µL or \>70.0 10\*4/µL
Time frame: 52 weeks
Population: Safety population - all patients who received at least one dose of study drug. Only participants with the required measurements were included for each specific value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hematocrit - female (n = 121, 38) | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hemoglobin - female (n = 121, 38) | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | White cell count - <2800/µL | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hemoglobin - male (n = 121, 38) | 3 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Platelets - <7.5 10*4/µL | 1 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hematocrit - male (n = 121, 38) | 3 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Platelets - >70.0 10*4/µL | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | White cell count - >16000/µL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Platelets - >70.0 10*4/µL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hemoglobin - male (n = 121, 38) | 2 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hemoglobin - female (n = 121, 38) | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hematocrit - male (n = 121, 38) | 4 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hematocrit - female (n = 121, 38) | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | White cell count - >16000/µL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Platelets - <7.5 10*4/µL | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | White cell count - <2800/µL | 1 participants |
Secondary
Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period
Clinically notable vital sign values were: pulse rate - low, \<40 bpm or \<=50 bpm and decrease from baseline \>=15bpm; pulse rate high, \>130 bpm or \>=120bpm and increase from baseline \>=15 bpm. Systolic blood pressure - low, \<75 mmHg or \<=90 mmHg and decrease from baseline \>=20 mmHg; high, \>200 mmHg or \>=180 mmHg and increase from baseline \>=20 mmHg. Diastolic blood pressure - low, \<40 mmHg or \<=50 mmHg and decrease from baseline \>=15 mmHg; high, \>115 mmHg or \>=105 mmHg and increase from baseline \>=15 mmHg.
Time frame: 52 weeks
Population: Safety population - all patients who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Systolic blood pressure - high | 1 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Pulse rate - low or high | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Systolic blood pressure - low or high | 1 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Pulse rate - high | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Diastolic blood pressure - low | 1 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Systolic blood pressure - low | 0 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Diastolic blood pressure - high | 2 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Diastolic blood pressure - low or high | 3 participants |
| NVA237 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Pulse rate - low | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Diastolic blood pressure - low or high | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Pulse rate - low | 1 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Pulse rate - high | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Pulse rate - low or high | 1 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Systolic blood pressure - low | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Systolic blood pressure - high | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Systolic blood pressure - low or high | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Diastolic blood pressure - low | 0 participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | Diastolic blood pressure - high | 0 participants |
Secondary
Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period
Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms).
Time frame: 52 weeks
Population: Safety population - all patients who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVA237 | Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period | Increase from baseline 30 to 60 ms | 6 participants |
| NVA237 | Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period | Increase from baseline >60 ms | 2 participants |
| Tiotropium | Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period | Increase from baseline 30 to 60 ms | 1 participants |
| Tiotropium | Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period | Increase from baseline >60 ms | 0 participants |
Secondary
Time From Randomization Until the Start of the First Moderate or Severe COPD Exacerbation
Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required. Participants who withdraw from the study and do not experience a moderate or severe exacerbation are censored at the date of withdrawal. Participants who complete the study and do not experience a moderate or severe exacerbation are censored at the completion visit date.
Time frame: 52 weeks
Population: Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVA237 | Time From Randomization Until the Start of the First Moderate or Severe COPD Exacerbation | 362 days |
| Tiotropium | Time From Randomization Until the Start of the First Moderate or Severe COPD Exacerbation | 359 days |