Chronic Obstructive Pulmonary Disease, COPD
Conditions
Brief summary
The study is a multicenter, randomized, 2-period, open-label, two arm, cross-over study to show the superior effect of a 4 week treatment each with QVA149 versus tiotropium on lung function. Similarly, this study aims to evaluate patient preference after experiencing both treatment regimens in patients with a clinical diagnosis of COPD (GOLD 2013) and a moderate to severe airflow limitation who are symptomatic (defined as CAT score of at least 10) at screening despite being treated with tiotropium
Interventions
DRUGQVA149
QVA149 capsules 110/50 µg for inhalation via Concep-1-inhaler device, taken once a day
DRUGTiotropium
Tiotropium 18 µg capsules for inhalation via HandiHaler device taken once a day
Sponsors
Novartis Pharmaceuticals
Study design
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* signed an Informed Consent Form * stable COPD according to current guidelines (GOLD 2013) * airflow limitation indicated by a post-bronchodilator FEV1/FVC ratio of \<0.70 and a post-bronchodilator FEV1 of ≥30% and \<80% of predicted normal values at Visit 2. * current or ex-smokers who have a smoking history of at least 10 pack years * Patients on stable tiotropium (18 µg/d) monotherapy for at least 8 weeks before Visit 1 * Symptomatic patients defined as patients with CAT score ≥ 10 at Visit 1 (Screening).
Exclusion criteria
* Pregnant or breast feeding mothers * Patients with conditions contraindicated for treatment * Patients with a history of clinically significant diseases * Patients who have a clinically significant renal disease * Patients with myocardial infarctions less than 6 months prior to study entry * Patients with recent (less than 1 year) history of NYHA Class III/IV left ventricular failure. * Patients with narrow-angle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or urinary retention * Patients with a history of malignancy of any organ system * Patients who have had a COPD exacerbation that required treatment with antibiotics, and/or systemic steroids (oral or intravenous) and/or hospitalization in the 6 weeks prior to Screening * Patients who have had a respiratory tract infection within 6 weeks prior to Screening * Patients with any history of asthma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in One Second (FEV1) at 1 h Post-inhalation | week 4 | Forced Expiratory Volume in one second (FEV1) will be calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Preference After Experiencing Both Treatments Was Assessed at the End of Treatment Period 2 With a Patient Preference Questionnaire. | 8 weeks | Patient preference after experiencing both treatments. The patient's preference questionnaire was a two-choice question (preference for QVA149 OR Tiotropium. |
| Investigator Preference Per Patient After Experiencing Both Treatments for Future Suggestions. | 8 weeks | The investigator preference for future treatment suggestion after experiencing both treatments was assessed at the end of treatment period 2 with the Investigator Preference Questionnaire |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence 1 QVA149 from day 1 to day 28 and tiotropium from day 29 to day 56 | 40 |
| Treatment Sequence 2 Tiotropium from day 1 to day 28 and QVA149 from day 29 to day 56 | 48 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Treatment Sequence 1 | Treatment Sequence 2 | Total |
|---|---|---|---|
| Age, Continuous | 63.9 Years STANDARD_DEVIATION 9.83 | 66.0 Years STANDARD_DEVIATION 9.31 | 65 Years STANDARD_DEVIATION 9.56 |
| Sex: Female, Male Female | 15 Participants | 16 Participants | 31 Participants |
| Sex: Female, Male Male | 25 Participants | 32 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 88 | 21 / 88 |
| serious Total, serious adverse events | 1 / 88 | 0 / 88 |
Outcome results
Primary
Forced Expiratory Volume in One Second (FEV1) at 1 h Post-inhalation
Forced Expiratory Volume in one second (FEV1) will be calculated as the volume of air forcibly exhaled in one second as measured by a spirometer.
Time frame: week 4
Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 | Forced Expiratory Volume in One Second (FEV1) at 1 h Post-inhalation | 1.676 Liters | 95% Confidence Interval 0.5709 |
| Tiotropium | Forced Expiratory Volume in One Second (FEV1) at 1 h Post-inhalation | 1.595 Liters | 95% Confidence Interval 0.6 |
p-value: 0.001795% CI: [0.031, 0.13]ANCOVA
Secondary
Investigator Preference Per Patient After Experiencing Both Treatments for Future Suggestions.
The investigator preference for future treatment suggestion after experiencing both treatments was assessed at the end of treatment period 2 with the Investigator Preference Questionnaire
Time frame: 8 weeks
Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period. One patient with missing data for this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QVA149 | Investigator Preference Per Patient After Experiencing Both Treatments for Future Suggestions. | 71 Participants |
| Tiotropium | Investigator Preference Per Patient After Experiencing Both Treatments for Future Suggestions. | 16 Participants |
Secondary
Patient Preference After Experiencing Both Treatments Was Assessed at the End of Treatment Period 2 With a Patient Preference Questionnaire.
Patient preference after experiencing both treatments. The patient's preference questionnaire was a two-choice question (preference for QVA149 OR Tiotropium.
Time frame: 8 weeks
Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period. Three patients were missing data for the patient preference analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QVA149 | Patient Preference After Experiencing Both Treatments Was Assessed at the End of Treatment Period 2 With a Patient Preference Questionnaire. | 59 Participants |
| Tiotropium | Patient Preference After Experiencing Both Treatments Was Assessed at the End of Treatment Period 2 With a Patient Preference Questionnaire. | 26 Participants |