Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, QVA149, NVA237, indacaterol, combination bronchodilator
Brief summary
This is a 52-week treatment, multi-center, randomized, open label, parallel group study to assess the long term safety and tolerability of once-daily QVA149 (indacaterol and NVA237 (\[glycopyrronium bromide\]) using tiotropium as an active control in Japanese patients with moderate to severe chronic obstructive pulmonary disease (COPD).
Interventions
DRUGQVA149
QVA149 (110 μg indacaterol / 50 μg glycopyrronium o.d.), delivered via Concept1
DRUGTiotropium
Tiotropium (18 μg o.d.), 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 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines 2008. * 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 etc.) * Patients with post-bronchodilator forced expiratory volume in one second (FEV1) ≥30% and \< 80% of the predicted normal, and post-bronchodilator FEV1/forced vital capacity (FVC) \< 0.7 at Visit 2.
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 4 weeks prior to Visit 1 * Patients with concomitant pulmonary disease * Patients with a history of asthma * Any patient with history of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years * 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 treatment with, or having a history of reactions/ hypersensitivity to anticholinergic agents, long and short acting beta-2 agonists, sympathomimetic amines Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Death | 52 weeks | An AE was the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event was not considered to be related to study drug. Study drug includes the investigational drug under evaluation and the comparator drug or placebo that was given during any phase of the study. Adverse events starting on or after the time of the first inhalation of study drug were classified as a treatment emergent adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the 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 Time-point 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 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 |
| Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Weeks 3, 6, 12, 24, 36, 52 | Pre-dose FEV1 is defined as the average of the measurements at 45 and 15 min pre-dose. Baseline is defined as the pre-dose FEV1 value on Day 1 (Week 1). |
| Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Weeks 3, 6, 12, 24, 36, 52 | Pre-dose FVC is defined as the average of the measurements at 45 and 15 min pre-dose. Baseline is defined as the pre-dose FVC value on Day 1 (Week 1). |
| Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period | 52 weeks | Clinically notable change from baseline was an increase from baseline of 30 or greater milliseconds (ms). |
Countries
Japan
Participant flow
Recruitment details
121 patients were randomized to the QVA149 group; however, demographics was on safety set and excluded 2 patients who did not take study drug
Pre-assignment details
There was a pre-screening visit where informed consent was obtained and current COPD medications reviewed and in suitable patients, if necessary, arrangements were made to adjust prohibited COPD therapy to allowable COPD therapy. The interval between Visit 2 and 3 was a 7-days run-in period used to assess eligibility and to collect baseline values.
Participants by arm
| Arm | Count |
|---|---|
| QVA149 QVA149 110/50 μg once a day (o.d) | 119 |
| Tiotropium tiotropium 18 μg o.d. | 39 |
| Total | 158 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | QVA149 | Tiotropium | Total |
|---|---|---|---|
| Age, Continuous | 69.3 years STANDARD_DEVIATION 6.79 | 69.4 years STANDARD_DEVIATION 6.9 | 69.3 years STANDARD_DEVIATION 6.8 |
| Baseline Body Mass Index | 22.31 kg/m^2 STANDARD_DEVIATION 3.067 | 23.02 kg/m^2 STANDARD_DEVIATION 2.919 | 22.49 kg/m^2 STANDARD_DEVIATION 3.037 |
| Baseline Height | 164.4 cm STANDARD_DEVIATION 7.08 | 163.3 cm STANDARD_DEVIATION 6.38 | 164.1 cm STANDARD_DEVIATION 6.91 |
| Baseline Weight | 60.38 kg STANDARD_DEVIATION 9.613 | 61.44 kg STANDARD_DEVIATION 8.788 | 60.64 kg STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 114 Participants | 37 Participants | 151 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 119 | 23 / 39 |
| serious Total, serious adverse events | 19 / 119 | 2 / 39 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Death
An AE was the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event was not considered to be related to study drug. Study drug includes the investigational drug under evaluation and the comparator drug or placebo that was given during any phase of the study. Adverse events starting on or after the time of the first inhalation of study drug were classified as a treatment emergent adverse event.
Time frame: 52 weeks
Population: The safety set included all patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Death | Adverse Events (AEs) | 101 Participants |
| QVA149 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Death | Serious Advers Events (SAEs) | 19 Participants |
| QVA149 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Death | Death | 1 Participants |
| Tiotropium | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Death | Adverse Events (AEs) | 28 Participants |
| Tiotropium | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Death | Serious Advers Events (SAEs) | 2 Participants |
| Tiotropium | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Death | Death | 0 Participants |
Secondary
Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline
Pre-dose FEV1 is defined as the average of the measurements at 45 and 15 min pre-dose. Baseline is defined as the pre-dose FEV1 value on Day 1 (Week 1).
Time frame: Weeks 3, 6, 12, 24, 36, 52
Population: Full Analysis Set (FAS) included all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 3 (117, 38) | 0.206 Litres | Standard Deviation 0.1534 |
| QVA149 | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 6 (115, 38) | 0.202 Litres | Standard Deviation 0.1668 |
| QVA149 | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 12 (113, 38) | 0.209 Litres | Standard Deviation 0.1725 |
| QVA149 | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 24 (113, 37) | 0.198 Litres | Standard Deviation 0.1735 |
| QVA149 | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 36 (105, 37) | 0.182 Litres | Standard Deviation 0.1619 |
| QVA149 | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 52 (104, 37) | 0.189 Litres | Standard Deviation 0.1762 |
| Tiotropium | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 36 (105, 37) | 0.082 Litres | Standard Deviation 0.1465 |
| Tiotropium | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 3 (117, 38) | 0.093 Litres | Standard Deviation 0.0977 |
| Tiotropium | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 24 (113, 37) | 0.115 Litres | Standard Deviation 0.14 |
| Tiotropium | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 6 (115, 38) | 0.083 Litres | Standard Deviation 0.1201 |
| Tiotropium | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 52 (104, 37) | 0.052 Litres | Standard Deviation 0.1688 |
| Tiotropium | Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline | Week 12 (113, 38) | 0.139 Litres | Standard Deviation 0.1562 |
Secondary
Change in Pre-dose Forced Vital Capacity (FVC) From Baseline
Pre-dose FVC is defined as the average of the measurements at 45 and 15 min pre-dose. Baseline is defined as the pre-dose FVC value on Day 1 (Week 1).
Time frame: Weeks 3, 6, 12, 24, 36, 52
Population: Full Analysis Set (FAS) included all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 3 (117, 38) | 0.314 Litres | Standard Deviation 0.2882 |
| QVA149 | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 6 (115, 38) | 0.310 Litres | Standard Deviation 0.3178 |
| QVA149 | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 12 (113, 38) | 0.335 Litres | Standard Deviation 0.2948 |
| QVA149 | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 24 (113, 37) | 0.330 Litres | Standard Deviation 0.3248 |
| QVA149 | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 36 (105, 37) | 0.264 Litres | Standard Deviation 0.2706 |
| QVA149 | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 52 (104, 37) | 0.261 Litres | Standard Deviation 0.3047 |
| Tiotropium | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 36 (105, 37) | 0.167 Litres | Standard Deviation 0.2438 |
| Tiotropium | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 3 (117, 38) | 0.213 Litres | Standard Deviation 0.2369 |
| Tiotropium | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 24 (113, 37) | 0.206 Litres | Standard Deviation 0.2367 |
| Tiotropium | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 6 (115, 38) | 0.173 Litres | Standard Deviation 0.2162 |
| Tiotropium | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 52 (104, 37) | 0.112 Litres | Standard Deviation 0.2462 |
| Tiotropium | Change in Pre-dose Forced Vital Capacity (FVC) From Baseline | Week 12 (113, 38) | 0.279 Litres | Standard Deviation 0.2942 |
Secondary
Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the 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: The safety set included all patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | Total protein - <4.0 g/dL (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | Total protein - > 9.5 g/dL (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | albumin <2.5 g/dL (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | bilirubin (total) >1.9 mg/dL (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | BUN >27 mg/dL (n = 118, 38) | 1 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | creatinine >1.99 mg/dL (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | AST >3 x ULN U/L (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | ALT >3 x ULN U/L (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | ALP >3 x ULN U/L (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | y-GTP >3 x ULN (n = 118, 38) | 2 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | sodium <125 mEq/L (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | sodium >160 mEq/L (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | potassium <3.0 mEq/ (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | potassium >6.0 mEq/ (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | glucose <51.0 mg/dL (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | glucose >180.0 mg/dL (n = 118, 38) | 7 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | glucose >180.0 mg/dL (n = 118, 38) | 3 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | Total protein - <4.0 g/dL (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | ALP >3 x ULN U/L (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | Total protein - > 9.5 g/dL (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | potassium <3.0 mEq/ (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | albumin <2.5 g/dL (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | y-GTP >3 x ULN (n = 118, 38) | 2 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | bilirubin (total) >1.9 mg/dL (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | glucose <51.0 mg/dL (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | BUN >27 mg/dL (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | sodium <125 mEq/L (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | creatinine >1.99 mg/dL (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | potassium >6.0 mEq/ (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | AST >3 x ULN U/L (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | sodium >160 mEq/L (n = 118, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period | ALT >3 x ULN U/L (n = 118, 38) | 0 Participants |
Secondary
Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period
Clinically notable change from baseline was an increase from baseline of 30 or greater milliseconds (ms).
Time frame: 52 weeks
Population: The safety set included all patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period | Males: QTc > 450 ms (n = 111, 36) | 6 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period | Females: QTc > 470 ms (n = 5, 2) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period | Increase from baseline 30 to 60 ms (n = 116, 38) | 12 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period | Increase from baseline > 60 ms (n = 116, 38) | 1 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period | Increase from baseline > 60 ms (n = 116, 38) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period | Males: QTc > 450 ms (n = 111, 36) | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period | Increase from baseline 30 to 60 ms (n = 116, 38) | 3 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period | Females: QTc > 470 ms (n = 5, 2) | 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: The safety set included all patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hemoglobin: female (n = 5, 2) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hemoglobin: male (n = 113, 36) | 3 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hematocrit: male (n = 113, 36) | 6 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hematocrit: female (n = 5, 2) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | White Cell Count < 2800 (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | White Cell Count > 2800 (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Platelets < 7.5 (n = 118, 38) | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Platelets > 70.0 (n = 118, 38) | 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 (n = 118, 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 < 2800 (n = 118, 38) | 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 = 113, 36) | 0 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 = 5, 2) | 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 (n = 118, 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 = 113, 36) | 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 (n = 118, 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: female (n = 5, 2) | 0 Participants |
Secondary
Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point 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: The safety set included all patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period | Pulse rate: high | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period | Systolic blood pressure - low or high | 4 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period | Systolic blood pressure - low | 4 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period | Diastolic blood pressure - low | 3 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period | Pulse rate: low or high | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period | Diastolic blood pressure - high | 2 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period | Systolic blood pressure - high | 0 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period | Diastolic blood pressure - low or high | 5 Participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point 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 Time-point Over the Whole Treatment Period | Diastolic blood pressure - low or high | 1 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point 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 Time-point 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 Time-point Over the Whole Treatment Period | Pulse rate: low or high | 0 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point 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 Time-point Over the Whole Treatment Period | Systolic blood pressure - high | 1 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period | Systolic blood pressure - low or high | 1 Participants |
| Tiotropium | Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point 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 Time-point Over the Whole Treatment Period | Diastolic blood pressure - high | 1 Participants |