Asthma
Conditions
Keywords
Asthma, QMF, Indacaterol, Mometasone
Brief summary
This study is designed to provide data about the 24 hours FEV1 profile, safety and tolerability of indacaterol/mometasone TWISTHALER device compared to placebo and using fluticasone/salmeterol as an active control.
Interventions
Fluticasone propionate/salmeterol 250/50 μg twice daily delivered via MDDPI.
Indacaterol maleate / mometasone furoate 500/400 μg once daily delivered via the TWISTHALER device.
DRUGplacebo to indacaterol/mometasone
Placebo to indacaterol maleate/mometasone furoate delivered via the TWISTHALER device.
DRUGplacebo to fluticasone propionate/salmeterol
Placebo to fluticasone propionate / salmeterol delivered via MDDPI.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male and female adult patients aged 18-75 years (inclusive), who have signed an Informed Consent Form prior to initiation of any study-related procedure, * Patients with persistent asthma, diagnosed according to Global Initiative for Asthma (GINA) guidelines (National Institute of Health, National Heart, Lung and Blood Institute, 2006) and who additionally meet the following criteria: * Patients receiving daily treatment with inhaled corticosteroid up to the maximum dose per day indicated in the product label, in a stable regimen for the month prior to Visit 1. * Patients with an FEV1 at Visit 1 ≥50% of predicted normal. * Patients who demonstrate an increase of ≥ 12% and ≥ 200 mL in FEV1 over their pre-bronchodilator.
Exclusion criteria
* Pregnant women, nursing mothers, or females of childbearing potential, regardless of whether or not sexually active, if they are not using a reliable form of contraception. * Patients who have used tobacco products within the 6 months period prior to Visit 1, or who have a smoking history of greater than 10 pack years. * Patients diagnosed with Chronic Obstructive Pulmonary disease (COPD) as defined by the GOLD guidelines (Global Initiative for Chronic Obstructive Lung Disease 2006). * Patients with seasonal allergy whose asthma is likely to deteriorate during the study period. * Patients who have had an acute asthma attack/exacerbation requiring hospitalization in the 6 months prior to Visit 1. * Patients who have had an acute asthma attack / exacerbation requiring an emergency room visit within 6 weeks prior to Visit 1 or at any time between Visit 1 and Visit 2. * Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1 or at any time between Visit 1 and Visit 2. * Patients with a history of long QT interval syndrome or whose QT interval corrected for heart rate (QTc) interval (Bazett's) measured at Visit 1 or Visit 2 is prolonged: \> 450 ms (males) or \> 470 ms (females). * Other clinically significant conditions which may interfere with the study conduct or patient safety as specified in the protocol. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) | Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16). | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from the period baseline to 24 hour post dose trough FEV1 after 1 day of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 5, 30 minutes, 1, 2, 3, 4 hours, 11 hours 10 minutes, 11 hours 45 minutes, 12 hours 30 minutes, 14, 16, 18, 20, 22 hours, 23 hours 10 minutes, and 23 hours 45 minutes post-dosing. | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect. |
| Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | Pre-dose, 5, 30 minutes, 1, 2, 3, 4 hours, 11 hours 10 minutes, 11 hours 45 minutes, 12 hours 30 minutes, 14, 16, 18, 20, 22 hours, 23 hours 10 minutes, and 23 hours 45 minutes post-dosing. | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was measured pre-dose and up to 24 hours post-dose. The FEV1 standardized area under the curve (AUC) was analyzed for four time intervals: * Baseline (pre-dose) to 4 hours (hr) post-dosing; * Baseline (pre-dose) to 23 hours, 45 minutes (min) post-dosing; * 11 hours, 10 minutes to 12 hours, 30 minutes post-dosing; * 11 hours, 10 minutes to 23 hours, 45 minutes post-dosing. AUC for FEV1 was analyzed using Analysis of Covariance adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect. |
| Time to Peak Forced Expiratory Volume in 1 Second (FEV1) | Up to 4 hours post-dose | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Time to peak FEV1 is calculated in minutes from the time of inhalation of study drug to the time of the peak FEV1 during the first 4 hours post-dose. Time to peak FEV1 is based on log-transformed analysis of variance adjusted for treatment, period, sequence and center, with patient nested within sequence as a random effect. Geometric Mean was obtained by taking anti-logs of the adjusted means from the model and standard error was calculated using the delta method. |
| Forced Vital Capacity (FVC) at Single Time Points | 5, 30 minutes, 1, 2, 3, 4 hours, 11 hours 10 minutes, 11 hours 45 minutes, 12 hours 30 minutes, 14, 16, 18, 20, 22 hours, 23 hours 10 minutes, and 23 hours 45 minutes post-dosing. | Vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was analyzed using ANCOVA adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect. |
Countries
Belgium, Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ind/M - FP/Salm - Pbo In Treatment Period 1 (Days 1 & 2) participants received indacaterol/mometasone (Ind/M) 500/400 μg via the TWISTHALER device (2 inhalations of 250/200 μg) in the evening and placebo to fluticasone/salmeterol via multi-dose dry powder inhaler (MDDPI), one inhalation in the evening and one inhalation the following morning.
In Treatment Period 2 (Days 8 & 9) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and fluticasone /salmeterol (FP/Salm) 250/50 μg via MDDPI, one inhalation in the evening and one inhalation the following morning.
In Treatment Period 3 (Days 15 & 16) participants received 2 inhalations of placebo (Pbo) to indacaterol/mometasone via the TWISTHALER device in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning.
Each treatment period was separated by a 6-day washout period. | 12 |
| FP/Salm - Pbo - Ind/M In Treatment Period 1 (Days 1 & 2) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and fluticasone/salmeterol (FP/Salm) 250/50 μg via MDDPI, one inhalation in the evening and one inhalation the following morning.
In Treatment Period 2 (Days 8 & 9) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning.
In Treatment Period 3 (Days 15 & 16) participants received indacaterol/mometasone (Ind/M) 500/400 μg via the TWISTHALER device (2 inhalations of 250/200 μg) in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning.
Each treatment period was separated by a 6-day washout period. | 12 |
| Pbo - Ind/M - FP/Salm In Treatment Period 1 (Days 1 & 2) participants received 2 inhalations of placebo (Pbo) to indacaterol/mometasone via the TWISTHALER device in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning.
In Treatment Period 2 (Days 8 & 9) participants received indacaterol/mometasone (Ind/M) 500/400 μg via the TWISTHALER device (2 inhalations of 250/200 μg) in the evening and placebo to fluticasone/salmeterol via MDDPI, one inhalation in the evening and one inhalation the following morning.
In Treatment Period 3 (Days 15 & 16) participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the evening and fluticasone/salmeterol (FP/Salm) 250/50 μg via MDDPI, one inhalation in the evening and one inhalation the following morning.
Each treatment period was separated by a 6-day washout period. | 13 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Treatment Period 1 | Adverse Event | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Ind/M - FP/Salm - Pbo | FP/Salm - Pbo - Ind/M | Pbo - Ind/M - FP/Salm | Total |
|---|---|---|---|---|
| Age Continuous | 40.2 years STANDARD_DEVIATION 15.37 | 50.5 years STANDARD_DEVIATION 12 | 52.5 years STANDARD_DEVIATION 10.46 | 47.9 years STANDARD_DEVIATION 13.51 |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 6 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 36 | 1 / 36 | 2 / 37 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 37 |
Outcome results
Primary
Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from the period baseline to 24 hour post dose trough FEV1 after 1 day of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Time frame: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16).
Population: The Intent-To-Treat (ITT) population included all randomized patients who had at least one period containing a Baseline FEV1 measurement and at least one post-baseline measurement of FEV1 for the same treatment period. Patients who took rescue medication within 6 hours prior to the trough measurements were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol/Mometasone | Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) | 0.081 liters | Standard Error 0.0473 |
| Fluticasone/Salmeterol | Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) | 0.049 liters | Standard Error 0.0472 |
| Placebo | Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) | -0.083 liters | Standard Error 0.0475 |
p-value: 0.00195% CI: [0.066, 0.263]ANCOVA
Secondary
Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Time frame: 5, 30 minutes, 1, 2, 3, 4 hours, 11 hours 10 minutes, 11 hours 45 minutes, 12 hours 30 minutes, 14, 16, 18, 20, 22 hours, 23 hours 10 minutes, and 23 hours 45 minutes post-dosing.
Population: Intent-to-treat population, where data were available. Patients who took rescue medication within 6 hours prior to spirometry measurements were excluded from the analysis. N indicates the number of participants with available data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 18 hours [N=35, 36, 33] | 2.729 liters | Standard Error 0.0395 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 11 hours 10 minutes [N=36, 35, 34] | 2.685 liters | Standard Error 0.0496 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 30 minutes [N=36, 36, 36] | 2.754 liters | Standard Error 0.0316 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 5 minutes [N=36, 36, 37] | 2.713 liters | Standard Error 0.0302 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 11 hours 45 minutes [N=36, 35, 32] | 2.628 liters | Standard Error 0.0492 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 23 hours 10 minutes [N=35, 36, 35] | 2.696 liters | Standard Error 0.0517 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 16 hours [N=36, 35, 31] | 2.720 liters | Standard Error 0.0493 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 12 hours 30 minutes [N=36, 35, 32] | 2.667 liters | Standard Error 0.0437 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 2 hours [N=36, 36, 36] | 2.754 liters | Standard Error 0.04 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 14 hours [N=36, 35, 32] | 2.766 liters | Standard Error 0.0433 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 24 hours post-dose trough [N=36, 36, 35] | 2.689 liters | Standard Error 0.0473 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 22 hours [N=35, 36, 34] | 2.674 liters | Standard Error 0.0493 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 3 hours [N=36, 36, 36] | 2.728 liters | Standard Error 0.0411 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 23 hours 45 minutes [N=36, 36, 34] | 2.686 liters | Standard Error 0.0459 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 20 hours [N=35, 36, 34] | 2.725 liters | Standard Error 0.0475 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 4 hours [N=36, 36, 35] | 2.705 liters | Standard Error 0.0434 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 1 hour [N=36, 36, 36] | 2.760 liters | Standard Error 0.035 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 16 hours [N=36, 35, 31] | 2.681 liters | Standard Error 0.0497 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 5 minutes [N=36, 36, 37] | 2.632 liters | Standard Error 0.0302 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 30 minutes [N=36, 36, 36] | 2.719 liters | Standard Error 0.0316 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 1 hour [N=36, 36, 36] | 2.771 liters | Standard Error 0.035 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 2 hours [N=36, 36, 36] | 2.734 liters | Standard Error 0.0399 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 3 hours [N=36, 36, 36] | 2.724 liters | Standard Error 0.041 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 4 hours [N=36, 36, 35] | 2.669 liters | Standard Error 0.0434 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 11 hours 10 minutes [N=36, 35, 34] | 2.570 liters | Standard Error 0.0499 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 11 hours 45 minutes [N=36, 35, 32] | 2.518 liters | Standard Error 0.0495 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 12 hours 30 minutes [N=36, 35, 32] | 2.659 liters | Standard Error 0.044 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 14 hours [N=36, 35, 32] | 2.779 liters | Standard Error 0.0436 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 18 hours [N=35, 36, 33] | 2.717 liters | Standard Error 0.0389 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 20 hours [N=35, 36, 34] | 2.707 liters | Standard Error 0.0467 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 22 hours [N=35, 36, 34] | 2.695 liters | Standard Error 0.0485 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 23 hours 10 minutes [N=35, 36, 35] | 2.676 liters | Standard Error 0.051 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 23 hours 45 minutes [N=36, 36, 34] | 2.640 liters | Standard Error 0.0458 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 24 hours post-dose trough [N=36, 36, 35] | 2.656 liters | Standard Error 0.0472 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 30 minutes [N=36, 36, 36] | 2.527 liters | Standard Error 0.0316 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 18 hours [N=35, 36, 33] | 2.513 liters | Standard Error 0.0398 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 3 hours [N=36, 36, 36] | 2.425 liters | Standard Error 0.0411 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 24 hours post-dose trough [N=36, 36, 35] | 2.524 liters | Standard Error 0.0475 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 20 hours [N=35, 36, 34] | 2.479 liters | Standard Error 0.0475 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 2 hours [N=36, 36, 36] | 2.483 liters | Standard Error 0.04 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 5 minutes [N=36, 36, 37] | 2.554 liters | Standard Error 0.03 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 22 hours [N=35, 36, 34] | 2.487 liters | Standard Error 0.0493 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 1 hour [N=36, 36, 36] | 2.525 liters | Standard Error 0.035 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 23 hours 45 minutes [N=36, 36, 34] | 2.523 liters | Standard Error 0.0464 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 12 hours 30 minutes [N=36, 35, 32] | 2.359 liters | Standard Error 0.0453 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 23 hours 10 minutes [N=35, 36, 35] | 2.530 liters | Standard Error 0.0513 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 14 hours [N=36, 35, 32] | 2.485 liters | Standard Error 0.0448 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 11 hours 45 minutes [N=36, 35, 32] | 2.276 liters | Standard Error 0.0509 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 11 hours 10 minutes [N=36, 35, 34] | 2.295 liters | Standard Error 0.0505 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 16 hours [N=36, 35, 31] | 2.454 liters | Standard Error 0.0515 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at Single Time Points | 4 hours [N=36, 36, 35] | 2.376 liters | Standard Error 0.0437 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was measured pre-dose and up to 24 hours post-dose. The FEV1 standardized area under the curve (AUC) was analyzed for four time intervals: * Baseline (pre-dose) to 4 hours (hr) post-dosing; * Baseline (pre-dose) to 23 hours, 45 minutes (min) post-dosing; * 11 hours, 10 minutes to 12 hours, 30 minutes post-dosing; * 11 hours, 10 minutes to 23 hours, 45 minutes post-dosing. AUC for FEV1 was analyzed using Analysis of Covariance adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Time frame: Pre-dose, 5, 30 minutes, 1, 2, 3, 4 hours, 11 hours 10 minutes, 11 hours 45 minutes, 12 hours 30 minutes, 14, 16, 18, 20, 22 hours, 23 hours 10 minutes, and 23 hours 45 minutes post-dosing.
Population: Intent-to-treat population, where data were available. Patients who took rescue medication within 6 hours prior to spirometry measurements were excluded from the analysis. N indicates the number of participants with available data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | Baseline to 4 hours [N=36, 36, 37] | 2.730 liters | Standard Error 0.0327 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | Baseline to 23 hours, 45 minutes [N=36, 36, 37] | 2.718 liters | Standard Error 0.0376 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | 11 hr, 10 min to 12 hr, 30 min [N=36, 35, 34] | 2.667 liters | Standard Error 0.0443 |
| Indacaterol/Mometasone | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | 11 hr, 10 min to 23 hr, 45min [N=36, 36, 36] | 2.726 liters | Standard Error 0.0435 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | 11 hr, 10 min to 23 hr, 45min [N=36, 36, 36] | 2.696 liters | Standard Error 0.0435 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | Baseline to 4 hours [N=36, 36, 37] | 2.713 liters | Standard Error 0.0327 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | 11 hr, 10 min to 12 hr, 30 min [N=36, 35, 34] | 2.585 liters | Standard Error 0.0445 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | Baseline to 23 hours, 45 minutes [N=36, 36, 37] | 2.679 liters | Standard Error 0.0376 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | 11 hr, 10 min to 23 hr, 45min [N=36, 36, 36] | 2.470 liters | Standard Error 0.0436 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | Baseline to 23 hours, 45 minutes [N=36, 36, 37] | 2.430 liters | Standard Error 0.0374 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | 11 hr, 10 min to 12 hr, 30 min [N=36, 35, 34] | 2.314 liters | Standard Error 0.0451 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Standardized Area Under the Curve (AUC) Between Baseline (Pre-dose) and 24 Hours Post-dose | Baseline to 4 hours [N=36, 36, 37] | 2.469 liters | Standard Error 0.0326 |
Secondary
Forced Vital Capacity (FVC) at Single Time Points
Vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was analyzed using ANCOVA adjusting for treatment, period, sequence and center with period baseline as a covariate and patient nested within sequence as a random effect.
Time frame: 5, 30 minutes, 1, 2, 3, 4 hours, 11 hours 10 minutes, 11 hours 45 minutes, 12 hours 30 minutes, 14, 16, 18, 20, 22 hours, 23 hours 10 minutes, and 23 hours 45 minutes post-dosing.
Population: Intent-to-treat population, where data were available. Patients who took rescue medication within 6 hours prior to spirometry measurements were excluded from the analysis. N indicates the number of participants with available data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 20 hours [N= 35, 36, 34] | 3.903 liters | Standard Error 0.0499 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 11 hours 45 minutes [N= 36, 35, 32] | 3.837 liters | Standard Error 0.0549 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 23 hours 45 minutes [N=36, 36, 34] | 3.866 liters | Standard Error 0.0509 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 18 hours [N= 35, 36, 33] | 3.893 liters | Standard Error 0.0462 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 12 hours 30 minutes [N= 36, 35, 32] | 3.833 liters | Standard Error 0.0496 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 2 hours [N= 36, 36, 36] | 4.080 liters | Standard Error 0.1074 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 16 hours [N= 36, 35, 31] | 3.896 liters | Standard Error 0.0524 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 14 hours [N= 36, 35, 32] | 3.918 liters | Standard Error 0.0506 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 3 hours [N= 36, 36, 36] | 3.925 liters | Standard Error 0.039 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 5 minutes [N= 36, 36, 37] | 3.917 liters | Standard Error 0.0333 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 23 hours 10 minutes [N= 35, 36, 35] | 3.870 liters | Standard Error 0.0519 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 4 hours [N= 36, 36, 35] | 3.857 liters | Standard Error 0.0438 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 1 hour [N= 36, 36, 36] | 3.945 liters | Standard Error 0.0337 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 22 hours [N= 35, 36, 34] | 3.865 liters | Standard Error 0.0453 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 11 hours 10 minutes [N= 36, 35, 34] | 3.896 liters | Standard Error 0.0569 |
| Indacaterol/Mometasone | Forced Vital Capacity (FVC) at Single Time Points | 30 minutes [N= 36, 36, 36] | 3.946 liters | Standard Error 0.0338 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 23 hours 10 minutes [N= 35, 36, 35] | 3.866 liters | Standard Error 0.0512 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 30 minutes [N= 36, 36, 36] | 3.933 liters | Standard Error 0.0338 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 1 hour [N= 36, 36, 36] | 3.955 liters | Standard Error 0.0337 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 3 hours [N= 36, 36, 36] | 3.923 liters | Standard Error 0.039 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 4 hours [N= 36, 36, 35] | 3.861 liters | Standard Error 0.0438 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 11 hours 10 minutes [N= 36, 35, 34] | 3.828 liters | Standard Error 0.0573 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 11 hours 45 minutes [N= 36, 35, 32] | 3.736 liters | Standard Error 0.0553 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 12 hours 30 minutes [N= 36, 35, 32] | 3.841 liters | Standard Error 0.05 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 14 hours [N= 36, 35, 32] | 3.894 liters | Standard Error 0.051 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 16 hours [N= 36, 35, 31] | 3.787 liters | Standard Error 0.0528 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 18 hours [N= 35, 36, 33] | 3.866 liters | Standard Error 0.0455 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 20 hours [N= 35, 36, 34] | 3.848 liters | Standard Error 0.0492 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 22 hours [N= 35, 36, 34] | 3.906 liters | Standard Error 0.0446 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 23 hours 45 minutes [N=36, 36, 34] | 3.825 liters | Standard Error 0.0509 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 5 minutes [N= 36, 36, 37] | 3.880 liters | Standard Error 0.0333 |
| Fluticasone/Salmeterol | Forced Vital Capacity (FVC) at Single Time Points | 2 hours [N= 36, 36, 36] | 3.899 liters | Standard Error 0.1073 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 11 hours 10 minutes [N= 36, 35, 34] | 3.632 liters | Standard Error 0.0581 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 2 hours [N= 36, 36, 36] | 3.742 liters | Standard Error 0.1073 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 20 hours [N= 35, 36, 34] | 3.764 liters | Standard Error 0.0499 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 4 hours [N= 36, 36, 35] | 3.665 liters | Standard Error 0.0442 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 5 minutes [N= 36, 36, 37] | 3.830 liters | Standard Error 0.0331 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 22 hours [N= 35, 36, 34] | 3.764 liters | Standard Error 0.0453 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 3 hours [N= 36, 36, 36] | 3.708 liters | Standard Error 0.0391 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 23 hours 10 minutes [N= 35, 36, 35] | 3.808 liters | Standard Error 0.0516 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 1 hour [N= 36, 36, 36] | 3.808 liters | Standard Error 0.0337 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 14 hours [N= 36, 35, 32] | 3.759 liters | Standard Error 0.0528 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 12 hours 30 minutes [N= 36, 35, 32] | 3.680 liters | Standard Error 0.0518 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 30 minutes [N= 36, 36, 36] | 3.839 liters | Standard Error 0.0338 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 16 hours [N= 36, 35, 31] | 3.737 liters | Standard Error 0.0551 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 11 hours 45 minutes [N= 36, 35, 32] | 3.607 liters | Standard Error 0.057 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 23 hours 45 minutes [N=36, 36, 34] | 3.817 liters | Standard Error 0.0516 |
| Placebo | Forced Vital Capacity (FVC) at Single Time Points | 18 hours [N= 35, 36, 33] | 3.784 liters | Standard Error 0.0466 |
Secondary
Time to Peak Forced Expiratory Volume in 1 Second (FEV1)
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Time to peak FEV1 is calculated in minutes from the time of inhalation of study drug to the time of the peak FEV1 during the first 4 hours post-dose. Time to peak FEV1 is based on log-transformed analysis of variance adjusted for treatment, period, sequence and center, with patient nested within sequence as a random effect. Geometric Mean was obtained by taking anti-logs of the adjusted means from the model and standard error was calculated using the delta method.
Time frame: Up to 4 hours post-dose
Population: Intent-to-treat population, where data were available. Patients who took rescue medication within 6 hours prior to spirometry measurements were excluded from the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol/Mometasone | Time to Peak Forced Expiratory Volume in 1 Second (FEV1) | 87.4 minutes | Standard Error 16.98 |
| Fluticasone/Salmeterol | Time to Peak Forced Expiratory Volume in 1 Second (FEV1) | 67.7 minutes | Standard Error 13.16 |
| Placebo | Time to Peak Forced Expiratory Volume in 1 Second (FEV1) | 22.3 minutes | Standard Error 4.3 |