Asthma
Conditions
Keywords
asthma, QAB149, indacaterol, pulmonary function
Brief summary
This study assessed the efficacy, safety, tolerability, and pharmacokinetics of two different formulations of indacaterol, one administered via the Concept1 device and one administered via the Simoon device. The study aimed to determine whether the novel formulation (Simoon) had a similar profile to that of the established formulation (Concept1).
Detailed description
This study was double-blind with regards to the Concept1, where placebo for the lactose-blended indacaterol was available. However, with regards to the Simoon, neither the subject nor the investigator was blinded due to lack of a placebo to the PulmoSphere formulation. Hence, the overall designation of the study was partially-blind.
Interventions
DRUGIndacaterol 150 μg via the Concept1 dry-powder inhaler
Indacaterol maleate 150 μg was provided in powder filled capsules with the Concept1 dry-powder inhaler.
DRUGIndacaterol 60 μg via the Simoon dry-powder inhaler
Indacaterol 60 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.
DRUGIndacaterol 120 μg via the Simoon dry-powder inhaler
Indacaterol 120 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.
DRUGPlacebo to indacaterol via the Concept1 dry-powder inhaler
Placebo to indacaterol was provided in powder filled capsules with the Concept1 dry-powder inhaler.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with persistent asthma with a forced expiratory volume in 1 second (FEV1) ≥ 50% * Patients using inhaled corticosteroid (with or without long-acting beta agonist)
Exclusion criteria
* Asthma exacerbations in previous 6 months * Chronic obstructive pulmonary disease (COPD) or other pulmonary disease * Excessive use of short-acting beta agonists Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose for Each Treatment | Baseline and Day 1 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose for each treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Indacaterol Exposure (AUC[0-24 Hours]) for Each Treatment | 0 to 24 hours post-dose | All patients fasted for at least 10 hours prior to administration of study medication and continued to fast for at least 4 hours thereafter. Venous blood samples for pharmacokinetic evaluation were collected at 5, 10, 15, and 30 minutes; and 1, 2, 4, 8, and 24 hours post-dose in each treatment period and were analyzed using a LC-MS/MS assay. Area under the concentration-time curve up to 24 hours (AUC\[0-24 hours\]) was calculated from concentration-time data using non-compartmental analysis. |
| Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | Baseline and Day 1 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 6, 8, and 12 hours post-dose in Day 1. |
| Time to Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | From 5 minutes to 12 hours post-dose | FEV1 was measured with spirometry conducted according to internationally accepted standards at 5, 15, and 30 minutes; 1 hour, 1 hour 30 minutes; and 1, 2, 4, 6, 8, and 12 hours post-dose in Day 1. |
| Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose for Each Treatment | From 5 minutes to 4 hours post-dose for each treatment | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. |
| Indacaterol Exposure (Cmax) for Each Treatment | 0 to 24 hours post-dose | All patients fasted for at least 10 hours prior to administration of study medication and continued to fast for at least 4 hours thereafter. Venous blood samples for pharmacokinetic evaluation were collected at 5, 10, 15, and 30 minutes; and 1, 2, 4, 8, and 24 hours post-dose in each treatment period and were analyzed using a LC-MS/MS assay. Maximum (peak) plasma drug concentration after drug administration (Cmax) was calculated from concentration-time data using non-compartmental analysis. |
Countries
Germany, Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population The entire study population included all 4 treatment groups who received indacaterol 150 µg via the Concept1 dry-powder inhaler (DPI), indacaterol 60 µg via the Simoon DPI, indacaterol 120 µg via the Simoon DPI, and placebo to indacaterol via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 1 | Adverse Event | 0 | 0 | 0 | 1 |
| Treatment Period 2 | Abnormal test procedure results | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 42.6 years STANDARD_DEVIATION 11.42 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 33 | 16 / 33 | 21 / 34 | 11 / 35 |
| serious Total, serious adverse events | 0 / 33 | 0 / 33 | 0 / 34 | 0 / 35 |
Outcome results
Primary
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose for Each Treatment
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose for each treatment.
Time frame: Baseline and Day 1
Population: Pharmacodynamic analysis set: All randomized patients that received at least 1 dose of study drug and had a baseline and at least 1 post-baseline measurement of FEV1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose for Each Treatment | 2.97 Liters | Standard Deviation 0.695 |
| Indacaterol 60 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose for Each Treatment | 2.93 Liters | Standard Deviation 0.688 |
| Indacaterol 120 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose for Each Treatment | 2.91 Liters | Standard Deviation 0.734 |
| Placebo to Indacaterol | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose for Each Treatment | 2.77 Liters | Standard Deviation 0.67 |
Secondary
Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 6, 8, and 12 hours post-dose in Day 1.
Time frame: Baseline and Day 1
Population: Pharmacodynamic analysis set: All randomized patients that received at least 1 dose of study drug and had a baseline and at least 1 post-baseline measurement of FEV1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | 3.19 Liters | Standard Deviation 0.747 |
| Indacaterol 60 μg | Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | 3.15 Liters | Standard Deviation 0.745 |
| Indacaterol 120 μg | Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | 3.15 Liters | Standard Deviation 0.717 |
| Placebo to Indacaterol | Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | 2.96 Liters | Standard Deviation 0.682 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose for Each Treatment
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time.
Time frame: From 5 minutes to 4 hours post-dose for each treatment
Population: Pharmacodynamic analysis set: All randomized patients that received at least 1 dose of study drug and had a baseline and at least 1 post-baseline measurement of FEV1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose for Each Treatment | 3.03 Liters | Standard Deviation 0.743 |
| Indacaterol 60 μg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose for Each Treatment | 2.96 Liters | Standard Deviation 0.732 |
| Indacaterol 120 μg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose for Each Treatment | 2.99 Liters | Standard Deviation 0.722 |
| Placebo to Indacaterol | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose for Each Treatment | 2.78 Liters | Standard Deviation 0.651 |
Secondary
Indacaterol Exposure (AUC[0-24 Hours]) for Each Treatment
All patients fasted for at least 10 hours prior to administration of study medication and continued to fast for at least 4 hours thereafter. Venous blood samples for pharmacokinetic evaluation were collected at 5, 10, 15, and 30 minutes; and 1, 2, 4, 8, and 24 hours post-dose in each treatment period and were analyzed using a LC-MS/MS assay. Area under the concentration-time curve up to 24 hours (AUC\[0-24 hours\]) was calculated from concentration-time data using non-compartmental analysis.
Time frame: 0 to 24 hours post-dose
Population: Pharmacokinetic analysis set: All randomized patients with evaluable pharmacokinetic data, ie, from which at least one pharmacokinetic parameter could be determined and sampling time information was available, from at least one treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Indacaterol Exposure (AUC[0-24 Hours]) for Each Treatment | 1119.2 pg*hr/mL | Standard Deviation 379.1 |
| Indacaterol 60 μg | Indacaterol Exposure (AUC[0-24 Hours]) for Each Treatment | 435.8 pg*hr/mL | Standard Deviation 245.7 |
| Indacaterol 120 μg | Indacaterol Exposure (AUC[0-24 Hours]) for Each Treatment | 849.4 pg*hr/mL | Standard Deviation 272.7 |
Secondary
Indacaterol Exposure (Cmax) for Each Treatment
All patients fasted for at least 10 hours prior to administration of study medication and continued to fast for at least 4 hours thereafter. Venous blood samples for pharmacokinetic evaluation were collected at 5, 10, 15, and 30 minutes; and 1, 2, 4, 8, and 24 hours post-dose in each treatment period and were analyzed using a LC-MS/MS assay. Maximum (peak) plasma drug concentration after drug administration (Cmax) was calculated from concentration-time data using non-compartmental analysis.
Time frame: 0 to 24 hours post-dose
Population: Pharmacokinetic analysis set: All randomized patients with evaluable pharmacokinetic data, ie, from which at least one pharmacokinetic parameter could be determined and sampling time information was available, from at least one treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Indacaterol Exposure (Cmax) for Each Treatment | 150.5 pg/mL | Standard Deviation 30.4 |
| Indacaterol 60 μg | Indacaterol Exposure (Cmax) for Each Treatment | 95.2 pg/mL | Standard Deviation 57.3 |
| Indacaterol 120 μg | Indacaterol Exposure (Cmax) for Each Treatment | 141.7 pg/mL | Standard Deviation 55 |
Secondary
Time to Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment
FEV1 was measured with spirometry conducted according to internationally accepted standards at 5, 15, and 30 minutes; 1 hour, 1 hour 30 minutes; and 1, 2, 4, 6, 8, and 12 hours post-dose in Day 1.
Time frame: From 5 minutes to 12 hours post-dose
Population: Pharmacodynamic analysis set: All randomized patients that received at least 1 dose of study drug and had a baseline and at least 1 post-baseline measurement of FEV1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Time to Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | 6.80 Hours | Standard Deviation 7.614 |
| Indacaterol 60 μg | Time to Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | 8.22 Hours | Standard Deviation 7.99 |
| Indacaterol 120 μg | Time to Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | 7.50 Hours | Standard Deviation 7.37 |
| Placebo to Indacaterol | Time to Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | 7.93 Hours | Standard Deviation 7.747 |