Chronic Obstructive Pulmonary Disease
Conditions
Keywords
QVA149, COPD, combination bronchodilator
Brief summary
The study is designed to provide long-term safety data for QVA149 in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
Interventions
DRUGQVA149
capsules for inhalation, delivered by an SDDPI
DRUGPlacebo
capsules for inhalation, delivered by an SDDPI
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female adults aged ≥40 yrs * Smoking history of at least 10 pack years * Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008) * Post-bronchodilator FEV1 \< 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) \<70%
Exclusion criteria
* Patients who have had a respiratory tract infection within 4 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 co-morbid 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 inhaled anticholinergic agents and β2 agonists * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events, Serious Adverse Events or Death | 52 weeks + Follow-up (Up to Day 394) | 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 |
|---|---|---|
| Pre-dose FEV1 | 52 weeks | Pre-dose FEV1 is defined as the average of the FEV1 15 minutes pre-dose and FEV1 45 minutes pre-dose. A mixed model was used with treatment as a fixed effect, average of 15 min and 45 min pre-dose FEV1 at visit 3 as the baseline measurement, and FEV1 prior to inhalation and FEV1 60 min post inhalation of two short acting bronchodialators as covariates. The model also included smoking status at baseline, history of ICS use and country as fixed effects with center nested within country as a random effect. |
| 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 \<115g/L, female \<95 g/L; hematocrit - male \<0.37v/v, female \<0.32v/v; white cell count - \<2.8 10E9/L or \>16.0 10E9/L; platelets - \<75 10E9/L or \>700 10E9/L |
| 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: sodium \<125mmol/L or \>160mmol/L; potassium \<3.0mmol/L or \>6.0mmol/L; BUN \>9.99mmol/L; creatinine \>176.8µmol/L; total protein (serum) \<40g/L or \>95g/L; albumin \<25g/L; bilirubin (total) \>34.2µmol/L; SGPT \>3 x ULN; SGOT \> 3 x ULN; gamma glutamyltransferase \>3 x ULN; alkaline phosphatase (serum) \>3 x ULN; glucose \<2.78mmol/L or \>9.99mmol/L |
| 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). |
Countries
Canada, France, Hungary, India, Latvia, Lithuania, Romania, South Africa, South Korea, United Kingdom
Participant flow
Pre-assignment details
Randomization ratio in the study was 2:1 for QVA149 and Placebo groups. Patients were not stratified by COPD disease severity.
Participants by arm
| Arm | Count |
|---|---|
| QVA149 110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI) | 225 |
| Placebo Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI | 113 |
| Total | 338 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal Test Procedure Result(s) | 1 | 0 |
| Overall Study | Adverse Event | 10 | 6 |
| Overall Study | Death | 3 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Protocol Deviation | 2 | 5 |
| Overall Study | Unsatisfactory Therapeutic Effect | 3 | 3 |
| Overall Study | Withdrawal by Subject | 11 | 6 |
Baseline characteristics
| Characteristic | QVA149 | Placebo | Total |
|---|---|---|---|
| Age Continuous | 62.5 years STANDARD_DEVIATION 8.81 | 62.9 years STANDARD_DEVIATION 8.14 | 62.6 years STANDARD_DEVIATION 8.58 |
| Sex: Female, Male Female | 51 Participants | 27 Participants | 78 Participants |
| Sex: Female, Male Male | 174 Participants | 86 Participants | 260 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 82 / 225 | 41 / 113 |
| serious Total, serious adverse events | 37 / 225 | 12 / 113 |
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 + Follow-up (Up to Day 394)
Population: Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with safety assessments were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 | Number of Participants With Adverse Events, Serious Adverse Events or Death | Death - 1st treatment day to 30d after last dose | 4 participants |
| QVA149 | Number of Participants With Adverse Events, Serious Adverse Events or Death | Death - last dose + 30d until end of follow-up | 1 participants |
| QVA149 | Number of Participants With Adverse Events, Serious Adverse Events or Death | Adverse events | 130 participants |
| QVA149 | Number of Participants With Adverse Events, Serious Adverse Events or Death | Serious adverse events | 37 participants |
| Placebo | Number of Participants With Adverse Events, Serious Adverse Events or Death | Serious adverse events | 12 participants |
| Placebo | Number of Participants With Adverse Events, Serious Adverse Events or Death | Death - 1st treatment day to 30d after last dose | 1 participants |
| Placebo | Number of Participants With Adverse Events, Serious Adverse Events or Death | Adverse events | 64 participants |
| Placebo | Number of Participants With Adverse Events, Serious Adverse Events or Death | Death - last dose + 30d until end of follow-up | 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: sodium \<125mmol/L or \>160mmol/L; potassium \<3.0mmol/L or \>6.0mmol/L; BUN \>9.99mmol/L; creatinine \>176.8µmol/L; total protein (serum) \<40g/L or \>95g/L; albumin \<25g/L; bilirubin (total) \>34.2µmol/L; SGPT \>3 x ULN; SGOT \> 3 x ULN; gamma glutamyltransferase \>3 x ULN; alkaline phosphatase (serum) \>3 x ULN; glucose \<2.78mmol/L or \>9.99mmol/L
Time frame: 52 weeks
Population: Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with the required data were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Sodium - <125mmol/L | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Albumin - <25g/L | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Glucose - >9.99mmol/L | 16 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Sodium - >160mmol/L | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Potassium - <3.0mmol/L | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Potassium - >6.0mmol/L | 2 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | BUN - >9.99mmol/L | 14 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Creatinine - >176.8µmol/L | 1 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Total protein (serum) - <40g/L | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Total protein (serum) - >95g/L | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Bilirubin (total) - >34.2µmol/L (n = 213, 101) | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | SGPT - >3 x ULN | 2 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | SGOT - >3 x ULN | 1 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Gamma glutamyltransferase - >3 x ULN | 8 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Alkaline phosphatase, serum - >3 x ULN | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Glucose - <2.78mmol/L | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | SGOT - >3 x ULN | 2 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | BUN - >9.99mmol/L | 4 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Total protein (serum) - >95g/L | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Total protein (serum) - <40g/L | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Albumin - <25g/L | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Glucose - >9.99mmol/L | 3 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Sodium - <125mmol/L | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Gamma glutamyltransferase - >3 x ULN | 7 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Sodium - >160mmol/L | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Bilirubin (total) - >34.2µmol/L (n = 213, 101) | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Potassium - <3.0mmol/L | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Glucose - <2.78mmol/L | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Potassium - >6.0mmol/L | 1 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | SGPT - >3 x ULN | 1 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Alkaline phosphatase, serum - >3 x ULN | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Creatinine - >176.8µmol/L | 1 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 \<115g/L, female \<95 g/L; hematocrit - male \<0.37v/v, female \<0.32v/v; white cell count - \<2.8 10E9/L or \>16.0 10E9/L; platelets - \<75 10E9/L or \>700 10E9/L
Time frame: 52 weeks
Population: Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with the required data were included in this analysis.
| 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 | WBC (total) - >16.0 10E9/L (n = 214, 102) | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hemoglobin - female <95g/L (n = 50, 25) | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Platelet count (direct) - >700 10E9/L (n=214, 102) | 0 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hematocrit - male <0.37v/v (n = 164, 77) | 11 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Platelet count (direct) - <75 10E9/L (n = 214,102) | 1 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hematocrit - female <0.32v/v (n = 49, 25) | 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 <115g/L (n = 164, 77) | 9 participants |
| QVA149 | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | WBC (total) - <2.8 10E9/L (n = 214, 102) | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hemoglobin - male <115g/L (n = 164, 77) | 1 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | WBC (total) - >16.0 10E9/L (n = 214, 102) | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Platelet count (direct) - <75 10E9/L (n = 214,102) | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Platelet count (direct) - >700 10E9/L (n=214, 102) | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | WBC (total) - <2.8 10E9/L (n = 214, 102) | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hemoglobin - female <95g/L (n = 50, 25) | 0 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hematocrit - male <0.37v/v (n = 164, 77) | 3 participants |
| Placebo | Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Hematocrit - female <0.32v/v (n = 49, 25) | 0 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 whether or not they were randomized. Only patients with the required data were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 | 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 |
| QVA149 | 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 |
| QVA149 | 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 |
| QVA149 | 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 | 3 participants |
| QVA149 | 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 |
| QVA149 | 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 |
| Placebo | 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 | 3 participants |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
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 whether or not they were randomized. Only patients with the required data were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 | Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period | 30 to 60ms change from baseline | 7 participants |
| QVA149 | Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period | > 60ms change from baseline | 0 participants |
| Placebo | Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period | 30 to 60ms change from baseline | 5 participants |
| Placebo | Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period | > 60ms change from baseline | 1 participants |
Secondary
Pre-dose FEV1
Pre-dose FEV1 is defined as the average of the FEV1 15 minutes pre-dose and FEV1 45 minutes pre-dose. A mixed model was used with treatment as a fixed effect, average of 15 min and 45 min pre-dose FEV1 at visit 3 as the baseline measurement, and FEV1 prior to inhalation and FEV1 60 min post inhalation of two short acting bronchodialators as covariates. The model also included smoking status at baseline, history of ICS use and country as fixed effects with center nested within country as a random effect.
Time frame: 52 weeks
Population: Full analysis set - all randomized patients who received at least one dose of study drug. Only patients with the required data were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 | Pre-dose FEV1 | 1.607 Liter | Standard Error 0.023 |
| Placebo | Pre-dose FEV1 | 1.418 Liter | Standard Error 0.0297 |