Asthma
Conditions
Keywords
indacaterol acetate, asthma, GINA 2015, pediatrics
Brief summary
This study is designed to explore lung function effects of two doses of indacaterol acetate, 75 μg and 150 μg, in pediatric asthma patients 6-11 years old, and to compare the systemic exposure to indacaterol in plasma with historical data in adults, to identify an appropriate dose to Phase III evaluation.
Interventions
DRUGIndacaterol acetate 75 μg
Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler
DRUGIndacaterol acetate 150 μg
Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler
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
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Male and female children ≥ 6 years and \< 12 years with confirmed diagnosis of asthma for at least 1 year prior to study enrollment. * Written informed consent by parent(s)/legal guardian(s) and depending upon their age and local requirements a consent or assent for the patient. * Patients receiving daily treatment with a stable low dose Inhaled Corticosteroid (ICS) (with or without additional controller), or patients receiving daily treatment with a stable mid-dose ICS (monotherapy or together with LTRA) for at least 4 weeks prior to Screening, and able to tolerate fluticasone propionate 100 μg b.i.d. inhaler starting at Visit 1 (or soon after). * Patients with a pre-bronchodilator FEV1 ≥ 50% and ≤ 90% of the predicted normal value for the patient at the start and end of Run-in (Visits 101 and 199). * Patients who demonstrate an increase in FEV1 of 12% within 30 minutes after administration of 400 μg salbutamol/360 μg albuterol (or equivalent dose) at Visit 101. All patients must perform a reversibility test at Visit 101.
Exclusion criteria
* Patients taking a mid-dose ICS (per GINA guidelines) in combination with LABA or any patient taking high-dose ICS. * Evidence of unstable disease within 4 weeks prior to Screening (Visit 1). * Patients who have had an asthma attack/exacerbation requiring systemic steroids (SCS) or hospitalization or emergency room visit within 3 months prior to Visit 1 (Screening) or more than 3 separate exacerbations in the 12 months preceding Visit 1. * Suspected or documented bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Screening (Visit 1). * Prior intubation for asthma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratoty Volume in 1 Second (FEV1) | 2 weeks | Change from baseline in pre-dose trough FEV1 after 2 weeks of treatment with indacaterol acetate 75 μg o.d and 150 μg o.d. The primary endpoint is change from baseline in pre-dose trough FEV1 (mL) after 2 weeks of treatment. The pre-dose trough FEV1 (mL) is defined as the mean of the two FEV1 (mL), values measured at -45 min and -15 min pre-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Asthma Control as Assessed by Pediatric Interviewer-administered Asthma Control Questionnaire | 2 weeks | Asthma Control as assessed by pediatric interviewer-administered Asthma Control Questionnaire (ACQ-IA) score at week 2 (mean change). A decrease in the score shows an improvement. The scale ranges from 0 (no symptoms) to 6 (severe symptoms every day). Results are given as a change as compared from baseline |
| Pre-dose Morning and Evening Peak Expiratoty Flow (PEF) | 2 weeks | Pre-dose morning and evening PEF over 2 weeks of treatment as determined by electronic peak flow meter data (mean change) |
| Rescue Medication Usage (Mean Daiily Number of Puffs) | 2 weeks | Rescue medication usage over 2 weeks of treatment as determined by patient diary data for indacaterol acetate 75 μg and 150 μg o.d.Results given as mean change of puffs of rescue medication. |
| Systemic Exposure to Indacaterol in Plasma | day 1, day 14 | Systemic exposure to indacaterol in plasma following sparse pharmacokinetic (PK) sampling on Day 1 and Day 14 after inhalation of indacaterol acetate 75 μg and 150 μg. |
| Forced Expiratoty Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | 2 weeks | FEV1 and FVC at 30 minutes and 1-hour post dose at week 2 for indacaterol acetate 75 μg and 150 μg o.d. |
| Symptoms as Recorded by Patient E-diary (Mean Total Daily Symptom Score) | 2 weeks | Symptoms as recorded by patient e-diary for indacaterol acetate 75 μg and 150 μg o.d. (mean change) The scale rages from 0 (no problem) - 4 (very severe problems). |
| Symptoms as Recorded by Patient E-diary (Percentage of Asthma Symptoms Free Days) | 2 weeks | Symptoms as recorded by patient e-diary for indacaterol acetate 75 μg and 150 μg o.d. (mean change) |
| Rescue Medication Usage (Percentage of Rescue Medication Free Days) | 2 weeks | Rescue medication usage over 2 weeks of treatment as determined by patient diary data for indacaterol acetate 75 μg and 150 μg o.d. |
Countries
Belgium, Colombia, Croatia, Germany, Guatemala, Hungary, Philippines, Russia, Slovakia, South Africa, Turkey (Türkiye)
Participant flow
Pre-assignment details
randomized set : 80 participants (41 and 39) Full analysis set : 79 participants (41 and 38) safety set : 79 participants (41 and 38) per protocol set : 35 participants (35 and 34)
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol Acetate 150 μg o.d. Indacaterol acetate 150 μg o.d. delivered via Concept1 inhaler | 41 |
| Indacaterol Acetate 75 μg o.d. Indacaterol acetate 75 μg o.d. delivered via Concept1 inhaler | 39 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | randomized but not treated | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Indacaterol Acetate 150 μg o.d. | Indacaterol Acetate 75 μg o.d. | Total |
|---|---|---|---|
| Age, Continuous | 9.3 years STANDARD_DEVIATION 1.47 | 9.1 years STANDARD_DEVIATION 1.58 | 9.2 years STANDARD_DEVIATION 1.51 |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Caucasian | 17 Participants | 17 Participants | 34 Participants |
| Race/Ethnicity, Customized Native American | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Other | 16 Participants | 13 Participants | 29 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 28 Participants |
| Sex: Female, Male Male | 28 Participants | 24 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 38 |
| other Total, other adverse events | 3 / 41 | 13 / 38 |
| serious Total, serious adverse events | 0 / 41 | 0 / 38 |
Outcome results
Primary
Trough Forced Expiratoty Volume in 1 Second (FEV1)
Change from baseline in pre-dose trough FEV1 after 2 weeks of treatment with indacaterol acetate 75 μg o.d and 150 μg o.d. The primary endpoint is change from baseline in pre-dose trough FEV1 (mL) after 2 weeks of treatment. The pre-dose trough FEV1 (mL) is defined as the mean of the two FEV1 (mL), values measured at -45 min and -15 min pre-dose.
Time frame: 2 weeks
Population: full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol Acetate 150 μg o.d. | Trough Forced Expiratoty Volume in 1 Second (FEV1) | 0.171 L | Standard Deviation 0.1664 |
| Indacaterol Acetate 75 μg o.d. | Trough Forced Expiratoty Volume in 1 Second (FEV1) | 0.212 L | Standard Deviation 0.2521 |
Secondary
Asthma Control as Assessed by Pediatric Interviewer-administered Asthma Control Questionnaire
Asthma Control as assessed by pediatric interviewer-administered Asthma Control Questionnaire (ACQ-IA) score at week 2 (mean change). A decrease in the score shows an improvement. The scale ranges from 0 (no symptoms) to 6 (severe symptoms every day). Results are given as a change as compared from baseline
Time frame: 2 weeks
Population: full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol Acetate 150 μg o.d. | Asthma Control as Assessed by Pediatric Interviewer-administered Asthma Control Questionnaire | -0.375 score on a scale | Standard Deviation 0.3796 |
| Indacaterol Acetate 75 μg o.d. | Asthma Control as Assessed by Pediatric Interviewer-administered Asthma Control Questionnaire | -0.270 score on a scale | Standard Deviation 0.6341 |
Secondary
Forced Expiratoty Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)
FEV1 and FVC at 30 minutes and 1-hour post dose at week 2 for indacaterol acetate 75 μg and 150 μg o.d.
Time frame: 2 weeks
Population: full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol Acetate 150 μg o.d. | Forced Expiratoty Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | 30 minutes | 0.234 L | Standard Deviation 0.1786 |
| Indacaterol Acetate 150 μg o.d. | Forced Expiratoty Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | 1 hour | 0.224 L | Standard Deviation 0.1725 |
| Indacaterol Acetate 75 μg o.d. | Forced Expiratoty Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | 30 minutes | 0.224 L | Standard Deviation 0.2459 |
| Indacaterol Acetate 75 μg o.d. | Forced Expiratoty Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | 1 hour | 0.258 L | Standard Deviation 0.2451 |
Secondary
Pre-dose Morning and Evening Peak Expiratoty Flow (PEF)
Pre-dose morning and evening PEF over 2 weeks of treatment as determined by electronic peak flow meter data (mean change)
Time frame: 2 weeks
Population: full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol Acetate 150 μg o.d. | Pre-dose Morning and Evening Peak Expiratoty Flow (PEF) | Morning PEF | 29.6 L/min | Standard Deviation 26.41 |
| Indacaterol Acetate 150 μg o.d. | Pre-dose Morning and Evening Peak Expiratoty Flow (PEF) | Evening PEF | 29.7 L/min | Standard Deviation 25.57 |
| Indacaterol Acetate 75 μg o.d. | Pre-dose Morning and Evening Peak Expiratoty Flow (PEF) | Morning PEF | 14.7 L/min | Standard Deviation 29.38 |
| Indacaterol Acetate 75 μg o.d. | Pre-dose Morning and Evening Peak Expiratoty Flow (PEF) | Evening PEF | 15.2 L/min | Standard Deviation 28.58 |
Secondary
Rescue Medication Usage (Mean Daiily Number of Puffs)
Rescue medication usage over 2 weeks of treatment as determined by patient diary data for indacaterol acetate 75 μg and 150 μg o.d.Results given as mean change of puffs of rescue medication.
Time frame: 2 weeks
Population: full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol Acetate 150 μg o.d. | Rescue Medication Usage (Mean Daiily Number of Puffs) | -0.19 number of puffs | Standard Deviation 1.479 |
| Indacaterol Acetate 75 μg o.d. | Rescue Medication Usage (Mean Daiily Number of Puffs) | -0.22 number of puffs | Standard Deviation 0.93 |
Secondary
Rescue Medication Usage (Percentage of Rescue Medication Free Days)
Rescue medication usage over 2 weeks of treatment as determined by patient diary data for indacaterol acetate 75 μg and 150 μg o.d.
Time frame: 2 weeks
Population: full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol Acetate 150 μg o.d. | Rescue Medication Usage (Percentage of Rescue Medication Free Days) | 7.4 percentage | Standard Deviation 22.37 |
| Indacaterol Acetate 75 μg o.d. | Rescue Medication Usage (Percentage of Rescue Medication Free Days) | 3.1 percentage | Standard Deviation 19.42 |
Secondary
Symptoms as Recorded by Patient E-diary (Mean Total Daily Symptom Score)
Symptoms as recorded by patient e-diary for indacaterol acetate 75 μg and 150 μg o.d. (mean change) The scale rages from 0 (no problem) - 4 (very severe problems).
Time frame: 2 weeks
Population: full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol Acetate 150 μg o.d. | Symptoms as Recorded by Patient E-diary (Mean Total Daily Symptom Score) | -0.18 score on a scale | Standard Deviation 0.695 |
| Indacaterol Acetate 75 μg o.d. | Symptoms as Recorded by Patient E-diary (Mean Total Daily Symptom Score) | 0.08 score on a scale | Standard Deviation 0.365 |
Secondary
Symptoms as Recorded by Patient E-diary (Percentage of Asthma Symptoms Free Days)
Symptoms as recorded by patient e-diary for indacaterol acetate 75 μg and 150 μg o.d. (mean change)
Time frame: 2 weeks
Population: full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol Acetate 150 μg o.d. | Symptoms as Recorded by Patient E-diary (Percentage of Asthma Symptoms Free Days) | 12.3 percentage | Standard Deviation 21.25 |
| Indacaterol Acetate 75 μg o.d. | Symptoms as Recorded by Patient E-diary (Percentage of Asthma Symptoms Free Days) | 4.4 percentage | Standard Deviation 26.6 |
Secondary
Systemic Exposure to Indacaterol in Plasma
Systemic exposure to indacaterol in plasma following sparse pharmacokinetic (PK) sampling on Day 1 and Day 14 after inhalation of indacaterol acetate 75 μg and 150 μg.
Time frame: day 1, day 14
Population: safety set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol Acetate 150 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 1 <=-2 hours | 0.0 pg/mL | Standard Deviation 0 |
| Indacaterol Acetate 150 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 1, 15 minutes | 204.1 pg/mL | Standard Deviation 98.27 |
| Indacaterol Acetate 150 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 1, 1 hour | 125.8 pg/mL | Standard Deviation 63.13 |
| Indacaterol Acetate 150 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 14 <=-2 hours | 80.9 pg/mL | Standard Deviation 32.51 |
| Indacaterol Acetate 150 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 14, 15 minutes | 393.1 pg/mL | Standard Deviation 182.11 |
| Indacaterol Acetate 150 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 14, 1 hour | 255.5 pg/mL | Standard Deviation 117.67 |
| Indacaterol Acetate 75 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 14, 15 minutes | 137.3 pg/mL | Standard Deviation 47.43 |
| Indacaterol Acetate 75 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 1 <=-2 hours | 0.0 pg/mL | Standard Deviation 0 |
| Indacaterol Acetate 75 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 14 <=-2 hours | 46.7 pg/mL | Standard Deviation 29.61 |
| Indacaterol Acetate 75 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 1, 15 minutes | 73.7 pg/mL | Standard Deviation 39.55 |
| Indacaterol Acetate 75 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 14, 1 hour | 103.0 pg/mL | Standard Deviation 37.88 |
| Indacaterol Acetate 75 μg o.d. | Systemic Exposure to Indacaterol in Plasma | Day 1, 1 hour | 43.9 pg/mL | Standard Deviation 20.84 |