Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, QVA149, nocturnal oxygen levels, combination bronchodilator
Brief summary
The purpose of this study was to determine whether a fixed dose combination of indacaterol and glycopyrronium (QVA149) has an impact on night-time blood oxygen levels in Chronic Obstructive Pulmonary Disease.
Interventions
DRUGQVA149
Delivered once daily via single-dose dry powder inhaler
DRUGQVA149 Placebo
Placebo delivered once daily via single-dose dry powder inhaler
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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
* Clinical diagnosis of COPD (according to GOLD guidelines, updated 2014) with a post-bronchodilator FEV1/FVC \<0.70 * Patients with a post-bronchodilator FEV1 ≥30% and \<60% of the predicted normal value * Resting daytime oxygen saturation levels measured by pulse oximetry of ≤95% SpO2 * 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)
Exclusion criteria
* An exacerbation of COPD (treatment with oral or parenteral antibiotics and/or glucocorticosteroids and/or hospitalization related to COPD) within 4 weeks prior to screening or during the run-in period * Diagnosed asthma * Patients receiving regular long term oxygen therapy (LTOT) * Ongoing / planned rehabilitation during the study period * Three or more awakenings during the night leading to toilet visit or other reasons for exiting the bed during the last week prior to the screening visit due to non-COPD reasons Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Night-time Blood Oxygenation | Post 4 weeks administration of QVA149, post 4 weeks administration of placebo | The mean night-time blood oxygenation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Time Spent During the Night Below 90 % in Blood Oxygen Saturation | Post 4 weeks administration of QVA149, post 4 weeks administration of placebo | The time during the night spent below 90 % in blood oxygen saturation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy. |
Countries
Denmark, Norway, Sweden
Participant flow
Pre-assignment details
Participants were randomized in a 1:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| All Participants (QVA149/Placebo) Participants received 4 weeks of QVA149 and 4 weeks of placebo according to either of the following sequences: QVA149 first and then placebo, or placebo first and then QVA149. | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Participants required other treatment. | 2 | 3 |
| Period 1 | Withdrawal by Subject | 1 | 0 |
| Period 2 | Adverse Event | 1 | 0 |
| Period 2 | COPD exacerbation | 1 | 0 |
| Period 2 | Participant required other treatment. | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants (QVA149/Placebo) |
|---|---|
| Age, Continuous | 68.4 Years STANDARD_DEVIATION 6.2 |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 35 | 12 / 34 |
| serious Total, serious adverse events | 1 / 35 | 1 / 34 |
Outcome results
Primary
Mean Night-time Blood Oxygenation
The mean night-time blood oxygenation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy.
Time frame: Post 4 weeks administration of QVA149, post 4 weeks administration of placebo
Population: Only randomized participants with data from both treatments were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 (Indacaterol/Glycopyrronium) | Mean Night-time Blood Oxygenation | 89.59 Percent Oxygenation | Standard Error 0.3 |
| Placebo | Mean Night-time Blood Oxygenation | 90.04 Percent Oxygenation | Standard Error 0.28 |
p-value: 0.241995% CI: [-1.21, 0.32]Mixed Models Analysis
Secondary
Percent of Time Spent During the Night Below 90 % in Blood Oxygen Saturation
The time during the night spent below 90 % in blood oxygen saturation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy.
Time frame: Post 4 weeks administration of QVA149, post 4 weeks administration of placebo
Population: Only randomized participants with data from both treatments were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 (Indacaterol/Glycopyrronium) | Percent of Time Spent During the Night Below 90 % in Blood Oxygen Saturation | 44.37 Percent | Standard Error 5.09 |
| Placebo | Percent of Time Spent During the Night Below 90 % in Blood Oxygen Saturation | 36.58 Percent | Standard Error 4.84 |
p-value: 0.201695% CI: [-4.51, 20.08]Mixed Models Analysis