Asthma
Conditions
Keywords
Asthma, Ciclesonide, children
Brief summary
The purpose of this study is to investigate the efficacy of inhaled ciclesonide at three different dose levels compared with placebo with respect to pulmonary function, asthma symptoms, and use of rescue medication in children aged 6-11 years with asthma. Treatment medication will be administered as follows: ciclesonide or placebo will be inhaled once daily in the evening. The study consists of a baseline period (2 to 4 weeks) and a treatment period (12 weeks). The study provides further data on safety and tolerability of ciclesonide.
Detailed description
The drug being tested is called ciclesonide. This study looked at the safety and efficacy of inhaled ciclesonide in children with asthma. The study enrolled 1080 patients. Participants were randomly assigned to 1 of 4 treatment groups which were undisclosed to the patient and study doctor during the study:• Ciclesonide 40 µg, 80 µg or 160 µg • Placebo- this is similar to study drug but has no active ingredient. Ciclesonide was inhaled via a metered-dose inhaler (MDI with HFA-134a propellant), with or without spacer, once daily in the evening throughout the study. All participants were asked to document daily AM and PM peak expiratory flow (PEF), daytime and nighttime asthma symptom scores and number of puffs of rescue medicine in an electronic diary. This multi-centre trial was conducted worldwide. The overall time to participate in this study was 20 weeks. Participants made multiple visits to the clinic plus a final visit 30 days after the last dose of study drug for a follow-up assessment.
Interventions
DRUGCiclesonide
inhaled Ciclesonide
DRUGPlacebo
Ciclesonide placebo-matching inhaler
DRUGSalbutamol
Salbutamol inhalation powder
Sponsors
Nycomed GmbH
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * History of asthma for at least 6 months * Ability to show optimal use of MDI, including inhalation technique * Lung function and reversibility within specified limits Main
Exclusion criteria
* Concomitant severe diseases * Diseases which are contraindications for the use of inhaled steroids * Two or more inpatient hospitalizations for asthma within the last year * Respiratory tract infection or asthma exacerbation within the last 30 days prior to entry into the study * Use of systemic steroids within the last 30 days prior to inclusion (depot steroids 6 weeks) * Beginning of or change in immunotherapy within the last 6 months prior to inclusion * Inability to follow the procedures of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Morning Peak Expiratory Flow (PEF) | Baseline and Week 12 | PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. The higher change from Baseline values are the best. Analysis of covariance (ANCOVA) model with the baseline value and age as covariates was used for analysis. Last observation carried forward. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication, Morning PEF and PEF Fluctuation | 28 days prior to last visit (Up to 12 Weeks) | Control of asthma was evaluated on a daily basis (24 hours) using the following variables: asthma symptoms, use of rescue medication, morning (am) PEF and PEF fluctuation. The median percentage of days with asthma control is presented. |
| Change From Baseline in Lung Function Variable Forced Expiratory Volume in One Second (FEV1) | Baseline and Week 12 | Spirometry was performed according to local standards. FEV1 is the maximal amount of air forcefully exhaled from the lungs in one second. Higher change numbers indicate better lung function. |
| Change From Baseline in Lung Function Variable PEF by Spirometry | Baseline and Week 12 | Spirometry was performed according to local standards. PEF is the maximum speed of expiration. Analysis was ANCOVA with factors value at Baseline, treatment, age, sex, center pool, ICS pretreatment, spacer use and asthma severity. Higher change numbers indicate better lung function. |
| Change From Baseline in Morning PEF From Diary | Baseline and Weeks 1 thru 12 | PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. The higher change from Baseline values are the best. Analysis of covariance (ANCOVA) model with the Baseline value and age as covariates was used for analysis. |
| Change From Baseline in Evening PEF From Diary | Baseline and Week 12 | PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. The higher change from Baseline values are the best. Analysis of covariance (ANCOVA) model with the Baseline value and age as covariates was used for analysis. |
| Time to First Event of Lack of Efficacy (LOE) by Week 12 | 12 weeks | Kaplan Meier Estimates of the probability of not experiencing LOE by Week 12 was measured. LOE was reached if any of the following criteria occurred during the treatment period: • asthma exacerbation (a worsening of asthma symptoms requiring a change in medication; • nocturnal awakenings due to asthma on any 4 or more nights during any 7-consecutive-day period; • use of more than 8 puffs/day of salbutamol on any 4 or more days during any 7-consecutive-day period; • decrease in morning PEF to \<80% of randomization value on any 4 consecutive days during the treatment period. |
| Change in Asthma Symptom Total Score | Baseline and Week 12 | Measurements of both nighttime and daytime asthma symptoms were assessed on a daily basis by the patient in the electronic diary, according to the following scales: Nighttime Asthma Score using a 5 point scale: 0=no asthma symptoms, slept through the night to 4=bad night, awake most of the night because of asthma. Daytime Asthma Score using a 5 point scale: 0=very well, no asthma symptoms to 4=asthma very bad, unable to carry out daily activities as usual. Total possible overall daily score range from 0(best) to 4 (worst). A negative change from Baseline indicated improvement. |
| Change in Use of Rescue Medications | Baseline and Week 12 | The daily use of rescue medication (salbutamol) was recorded in the electronic diary in the morning and the evening. A negative change from Baseline indicates improvement. |
| Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication and Morning PEF | 28 days prior to last visit (Up to 12 Weeks) | Control of asthma was evaluated on a daily basis (24 hours) using the following variables: asthma symptoms, use of rescue medication, and morning (am) PEF. The median percentage of days with asthma control is presented. |
| Change From Baseline in Pediatric Asthma Quality of Life Questionnaire Standard [PAQLQ(S)] Overall Score | Baseline and Week 12 | PAQLQS is a disease specific instrument to assess the impact of asthma on the patient's quality of life. The PAQLQS consists of 23 items in 3 domains evaluating activity limitations, symptoms and emotional function. Patients answered each question using a 7-point scale from 1= maximum impairment to 7=no impairment) about their experience during the previous week. Total possible score ranging from 23 (worst) to 161(best). Higher change from Baseline scores are the best. Analysis of covariance (ANCOVA) model with the baseline value and age as covariates was used for analysis. |
| Change From Baseline in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) Overall | Baseline and Week 12 | PACQLQ assesses the impact of the child's asthma on the quality of life of the caregiver. The PACQLQ consists of 13 items in 2 domains evaluating activity limitations and emotional function. Caregivers answered each question using a 7-point scale from 1= maximum impairment to 7=no impairment about their experience during the previous week. Total possible score ranging from 13 (worst) to 91(best). Higher change from Baseline scores are the best. Analysis of covariance (ANCOVA) model with the baseline value and age as covariates was used for analysis. |
| Change From Baseline in Diurnal PEF Fluctuations | Baseline and Week 12 | PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. A negative change from Baseline indicates improvement. Analysis of covariance (ANCOVA) model with the Baseline value and age as covariates was used for analysis. |
Countries
Bulgaria, Germany, Hungary, Poland, Romania, Russia, South Africa, Spain, Ukraine
Participant flow
Recruitment details
Participants took part in the study at 110 investigative sites in Bulgaria, Germany, Hungary, Poland, Romania, Russia, South Africa, Spain, and Ukraine from 29 September 2006 to 17 August 2007.
Pre-assignment details
Children with a diagnosis of asthma were enrolled equally in 1 of 4 treatment groups, once a day placebo, 40 µg, 80 µg or 160 µg ciclesonide.
Participants by arm
| Arm | Count |
|---|---|
| Ciclesonide 40 µg Placebo-matching ciclesonide, inhaled via a metered-dose inhaler (MDI) with 1,1,1,2-hydrofluoroalkane (HFA)-134a as propellant, once daily, in the evening for 2 to 4 weeks in the Baseline period followed by ciclesonide 40 µg, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed. | 305 |
| Ciclesonide 80 µg Placebo-matching ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily, in the evening for 2 to 4 weeks in the Baseline period followed by ciclesonide 80 µg, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed. | 312 |
| Ciclesonide 160 µg Placebo-matching ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily, in the evening for 2 to 4 weeks in the Baseline period followed by ciclesonide 160 µg, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed. | 310 |
| Placebo Placebo-matching Ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 2 to 4 week in the Baseline period followed by placebo-matching ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed. | 146 |
| Total | 1,073 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Reason Not Specified | 50 | 57 | 58 | 40 |
Baseline characteristics
| Characteristic | Total | Placebo | Ciclesonide 160 µg | Ciclesonide 80 µg | Ciclesonide 40 µg |
|---|---|---|---|---|---|
| Age, Continuous | 8.4 years STANDARD_DEVIATION 1.6 | 8.4 years STANDARD_DEVIATION 1.7 | 8.7 years STANDARD_DEVIATION 1.6 | 8.4 years STANDARD_DEVIATION 1.6 | 8.4 years STANDARD_DEVIATION 1.7 |
| Asthma Severity According to Global Initiative for Asthma (GINA) Intermittent | 59 participants | 7 participants | 13 participants | 19 participants | 20 participants |
| Asthma Severity According to Global Initiative for Asthma (GINA) Mild | 86 participants | 10 participants | 29 participants | 22 participants | 25 participants |
| Asthma Severity According to Global Initiative for Asthma (GINA) Moderate | 376 participants | 50 participants | 104 participants | 110 participants | 112 participants |
| Asthma Severity According to Global Initiative for Asthma (GINA) Severe | 552 participants | 79 participants | 164 participants | 161 participants | 148 participants |
| Duration of Asthma | 45.5 months STANDARD_DEVIATION 27.7 | 47.6 months STANDARD_DEVIATION 28 | 45.5 months STANDARD_DEVIATION 27.4 | 45.5 months STANDARD_DEVIATION 27.8 | 44.3 months STANDARD_DEVIATION 27.7 |
| Gender Female | 362 Participants | 54 Participants | 92 Participants | 121 Participants | 95 Participants |
| Gender Male | 711 Participants | 92 Participants | 218 Participants | 191 Participants | 210 Participants |
| Height | 134.9 cm STANDARD_DEVIATION 10.9 | 134.6 cm STANDARD_DEVIATION 11.1 | 135.9 cm STANDARD_DEVIATION 10.8 | 134.5 cm STANDARD_DEVIATION 11 | 134.6 cm STANDARD_DEVIATION 10.8 |
| ICS Pretreatment Dose | 214.8 µg/day STANDARD_DEVIATION 182.1 | 224.6 µg/day STANDARD_DEVIATION 178.8 | 205.0 µg/day STANDARD_DEVIATION 177.1 | 222.8 µg/day STANDARD_DEVIATION 188.8 | 211.9 µg/day STANDARD_DEVIATION 181.9 |
| Inhaled Glucocorticosteroids (ICS) Pretreatment No | 368 participants | 44 participants | 111 participants | 108 participants | 105 participants |
| Inhaled Glucocorticosteroids (ICS) Pretreatment Yes | 705 participants | 102 participants | 199 participants | 204 participants | 200 participants |
| Race/Ethnicity, Customized Caucasian | 965 participants | 133 participants | 277 participants | 279 participants | 276 participants |
| Race/Ethnicity, Customized non-Caucasian | 108 participants | 13 participants | 33 participants | 33 participants | 29 participants |
| Region of Enrollment Bulgaria | 110 participants | 15 participants | 33 participants | 33 participants | 29 participants |
| Region of Enrollment Germany | 53 participants | 8 participants | 12 participants | 16 participants | 17 participants |
| Region of Enrollment Hungary | 152 participants | 22 participants | 43 participants | 45 participants | 42 participants |
| Region of Enrollment Poland | 169 participants | 23 participants | 49 participants | 48 participants | 49 participants |
| Region of Enrollment Romania | 60 participants | 8 participants | 21 participants | 16 participants | 15 participants |
| Region of Enrollment Russian Federation | 188 participants | 27 participants | 55 participants | 52 participants | 54 participants |
| Region of Enrollment South Africa | 111 participants | 13 participants | 32 participants | 34 participants | 32 participants |
| Region of Enrollment Spain | 61 participants | 8 participants | 17 participants | 18 participants | 18 participants |
| Region of Enrollment Ukraine | 169 participants | 22 participants | 48 participants | 50 participants | 49 participants |
| Weight | 32.5 kg STANDARD_DEVIATION 9.4 | 32.7 kg STANDARD_DEVIATION 9.7 | 33.2 kg STANDARD_DEVIATION 9.5 | 31.9 kg STANDARD_DEVIATION 9.3 | 32.3 kg STANDARD_DEVIATION 9.1 |
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 | 49 / 305 | 45 / 312 | 45 / 310 | 14 / 146 |
| serious Total, serious adverse events | 4 / 305 | 5 / 312 | 2 / 310 | 1 / 146 |
Outcome results
Primary
Change From Baseline in Morning Peak Expiratory Flow (PEF)
PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. The higher change from Baseline values are the best. Analysis of covariance (ANCOVA) model with the baseline value and age as covariates was used for analysis. Last observation carried forward.
Time frame: Baseline and Week 12
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ciclesonide 40 µg | Change From Baseline in Morning Peak Expiratory Flow (PEF) | 15.23 liters/minute | Standard Error 2.69 |
| Ciclesonide 80 µg | Change From Baseline in Morning Peak Expiratory Flow (PEF) | 14.79 liters/minute | Standard Error 2.6 |
| Ciclesonide 160 µg | Change From Baseline in Morning Peak Expiratory Flow (PEF) | 17.37 liters/minute | Standard Error 2.68 |
| Placebo | Change From Baseline in Morning Peak Expiratory Flow (PEF) | 5.40 liters/minute | Standard Error 3.71 |
p-value: 0.011695% CI: [1.4, 18.3]ANCOVA
p-value: 0.014895% CI: [0.9, 17.8]ANCOVA
p-value: 0.002895% CI: [3.5, 20.4]ANCOVA
Secondary
Change From Baseline in Diurnal PEF Fluctuations
PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. A negative change from Baseline indicates improvement. Analysis of covariance (ANCOVA) model with the Baseline value and age as covariates was used for analysis.
Time frame: Baseline and Week 12
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ciclesonide 40 µg | Change From Baseline in Diurnal PEF Fluctuations | -0.841 percent change | Standard Deviation 9.942 |
| Ciclesonide 80 µg | Change From Baseline in Diurnal PEF Fluctuations | -1.209 percent change | Standard Deviation 10.686 |
| Ciclesonide 160 µg | Change From Baseline in Diurnal PEF Fluctuations | -1.192 percent change | Standard Deviation 11.29 |
| Placebo | Change From Baseline in Diurnal PEF Fluctuations | 0.214 percent change | Standard Deviation 9.453 |
Secondary
Change From Baseline in Evening PEF From Diary
PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. The higher change from Baseline values are the best. Analysis of covariance (ANCOVA) model with the Baseline value and age as covariates was used for analysis.
Time frame: Baseline and Week 12
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis. Last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ciclesonide 40 µg | Change From Baseline in Evening PEF From Diary | 10.16 liters/minute | Standard Error 2.54 |
| Ciclesonide 80 µg | Change From Baseline in Evening PEF From Diary | 9.37 liters/minute | Standard Error 2.46 |
| Ciclesonide 160 µg | Change From Baseline in Evening PEF From Diary | 12.71 liters/minute | Standard Error 2.53 |
| Placebo | Change From Baseline in Evening PEF From Diary | 4.02 liters/minute | Standard Error 3.52 |
Secondary
Change From Baseline in Lung Function Variable Forced Expiratory Volume in One Second (FEV1)
Spirometry was performed according to local standards. FEV1 is the maximal amount of air forcefully exhaled from the lungs in one second. Higher change numbers indicate better lung function.
Time frame: Baseline and Week 12
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ciclesonide 40 µg | Change From Baseline in Lung Function Variable Forced Expiratory Volume in One Second (FEV1) | 0.123 liters | Standard Error 0.015 |
| Ciclesonide 80 µg | Change From Baseline in Lung Function Variable Forced Expiratory Volume in One Second (FEV1) | 0.122 liters | Standard Error 0.015 |
| Ciclesonide 160 µg | Change From Baseline in Lung Function Variable Forced Expiratory Volume in One Second (FEV1) | 0.139 liters | Standard Error 0.015 |
| Placebo | Change From Baseline in Lung Function Variable Forced Expiratory Volume in One Second (FEV1) | 0.039 liters | Standard Error 0.022 |
Secondary
Change From Baseline in Lung Function Variable PEF by Spirometry
Spirometry was performed according to local standards. PEF is the maximum speed of expiration. Analysis was ANCOVA with factors value at Baseline, treatment, age, sex, center pool, ICS pretreatment, spacer use and asthma severity. Higher change numbers indicate better lung function.
Time frame: Baseline and Week 12
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis. Last Observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ciclesonide 40 µg | Change From Baseline in Lung Function Variable PEF by Spirometry | 20.68 liters/minute | Standard Error 2.61 |
| Ciclesonide 80 µg | Change From Baseline in Lung Function Variable PEF by Spirometry | 21.71 liters/minute | Standard Error 2.51 |
| Ciclesonide 160 µg | Change From Baseline in Lung Function Variable PEF by Spirometry | 22.25 liters/minute | Standard Error 2.61 |
| Placebo | Change From Baseline in Lung Function Variable PEF by Spirometry | 15.13 liters/minute | Standard Error 3.69 |
Secondary
Change From Baseline in Morning PEF From Diary
PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. The higher change from Baseline values are the best. Analysis of covariance (ANCOVA) model with the Baseline value and age as covariates was used for analysis.
Time frame: Baseline and Weeks 1 thru 12
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 1 (n=303,311,310,146) | 11.61 liters/minute | Standard Error 1.55 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 11 | 16.12 liters/minute | Standard Error 2.6 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 3 (n=304,312,310,146) | 11.36 liters/minute | Standard Error 2.08 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 2 (n=303,311,310,146) | 9.82 liters/minute | Standard Error 1.89 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 10 | 16.35 liters/minute | Standard Error 2.48 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 8 | 14.57 liters/minute | Standard Error 2.39 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 7 | 14.57 liters/minute | Standard Error 2.37 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 12 | 15.93 liters/minute | Standard Error 2.72 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 9 | 15.26 liters/minute | Standard Error 2.44 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 5 | 14.86 liters/minute | Standard Error 2.23 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 4 (n=304,312,310,146) | 13.63 liters/minute | Standard Error 2.18 |
| Ciclesonide 40 µg | Change From Baseline in Morning PEF From Diary | Change at Week 6 | 13.91 liters/minute | Standard Error 2.3 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 10 | 16.79 liters/minute | Standard Error 2.4 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 11 | 15.97 liters/minute | Standard Error 2.52 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 12 | 15.43 liters/minute | Standard Error 2.64 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 1 (n=303,311,310,146) | 9.20 liters/minute | Standard Error 1.5 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 2 (n=303,311,310,146) | 11.95 liters/minute | Standard Error 1.83 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 3 (n=304,312,310,146) | 11.11 liters/minute | Standard Error 2.01 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 4 (n=304,312,310,146) | 13.27 liters/minute | Standard Error 2.12 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 5 | 13.33 liters/minute | Standard Error 2.16 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 6 | 13.26 liters/minute | Standard Error 2.23 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 7 | 15.05 liters/minute | Standard Error 2.3 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 8 | 15.92 liters/minute | Standard Error 2.31 |
| Ciclesonide 80 µg | Change From Baseline in Morning PEF From Diary | Change at Week 9 | 16.02 liters/minute | Standard Error 2.36 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 9 | 13.23 liters/minute | Standard Error 2.43 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 7 | 14.14 liters/minute | Standard Error 2.36 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 12 | 17.59 liters/minute | Standard Error 2.71 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 11 | 16.24 liters/minute | Standard Error 2.59 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 10 | 14.59 liters/minute | Standard Error 2.47 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 6 | 14.71 liters/minute | Standard Error 2.29 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 2 (n=303,311,310,146) | 12.26 liters/minute | Standard Error 1.89 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 4 (n=304,312,310,146) | 15.60 liters/minute | Standard Error 2.18 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 1 (n=303,311,310,146) | 11.54 liters/minute | Standard Error 1.54 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 8 | 13.63 liters/minute | Standard Error 2.38 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 3 (n=304,312,310,146) | 13.15 liters/minute | Standard Error 2.07 |
| Ciclesonide 160 µg | Change From Baseline in Morning PEF From Diary | Change at Week 5 | 15.39 liters/minute | Standard Error 2.22 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 3 (n=304,312,310,146) | 6.74 liters/minute | Standard Error 2.87 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 8 | 7.05 liters/minute | Standard Error 3.3 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 4 (n=304,312,310,146) | 6.31 liters/minute | Standard Error 3.02 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 10 | 7.66 liters/minute | Standard Error 3.43 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 5 | 9.67 liters/minute | Standard Error 3.08 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 6 | 7.64 liters/minute | Standard Error 3.18 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 11 | 6.80 liters/minute | Standard Error 3.6 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 7 | 6.21 liters/minute | Standard Error 3.28 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 1 (n=303,311,310,146) | 4.54 liters/minute | Standard Error 2.13 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 9 | 7.88 liters/minute | Standard Error 3.37 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 2 (n=303,311,310,146) | 4.20 liters/minute | Standard Error 2.61 |
| Placebo | Change From Baseline in Morning PEF From Diary | Change at Week 12 | 6.41 liters/minute | Standard Error 3.76 |
Secondary
Change From Baseline in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) Overall
PACQLQ assesses the impact of the child's asthma on the quality of life of the caregiver. The PACQLQ consists of 13 items in 2 domains evaluating activity limitations and emotional function. Caregivers answered each question using a 7-point scale from 1= maximum impairment to 7=no impairment about their experience during the previous week. Total possible score ranging from 13 (worst) to 91(best). Higher change from Baseline scores are the best. Analysis of covariance (ANCOVA) model with the baseline value and age as covariates was used for analysis.
Time frame: Baseline and Week 12
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ciclesonide 40 µg | Change From Baseline in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) Overall | 0.82 score on a scale | Standard Error 0.08 |
| Ciclesonide 80 µg | Change From Baseline in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) Overall | 0.88 score on a scale | Standard Error 0.08 |
| Ciclesonide 160 µg | Change From Baseline in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) Overall | 0.84 score on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) Overall | 0.71 score on a scale | Standard Error 0.12 |
Secondary
Change From Baseline in Pediatric Asthma Quality of Life Questionnaire Standard [PAQLQ(S)] Overall Score
PAQLQS is a disease specific instrument to assess the impact of asthma on the patient's quality of life. The PAQLQS consists of 23 items in 3 domains evaluating activity limitations, symptoms and emotional function. Patients answered each question using a 7-point scale from 1= maximum impairment to 7=no impairment) about their experience during the previous week. Total possible score ranging from 23 (worst) to 161(best). Higher change from Baseline scores are the best. Analysis of covariance (ANCOVA) model with the baseline value and age as covariates was used for analysis.
Time frame: Baseline and Week 12
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ciclesonide 40 µg | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire Standard [PAQLQ(S)] Overall Score | 0.78 score on a scale | Standard Error 0.07 |
| Ciclesonide 80 µg | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire Standard [PAQLQ(S)] Overall Score | 0.71 score on a scale | Standard Error 0.07 |
| Ciclesonide 160 µg | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire Standard [PAQLQ(S)] Overall Score | 0.72 score on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire Standard [PAQLQ(S)] Overall Score | 0.43 score on a scale | Standard Error 0.1 |
Secondary
Change in Asthma Symptom Total Score
Measurements of both nighttime and daytime asthma symptoms were assessed on a daily basis by the patient in the electronic diary, according to the following scales: Nighttime Asthma Score using a 5 point scale: 0=no asthma symptoms, slept through the night to 4=bad night, awake most of the night because of asthma. Daytime Asthma Score using a 5 point scale: 0=very well, no asthma symptoms to 4=asthma very bad, unable to carry out daily activities as usual. Total possible overall daily score range from 0(best) to 4 (worst). A negative change from Baseline indicated improvement.
Time frame: Baseline and Week 12
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ciclesonide 40 µg | Change in Asthma Symptom Total Score | Asthma Total Symptom Score (n=304,312,310,146) | -0.916 score on a scale | Standard Deviation 1.265 |
| Ciclesonide 40 µg | Change in Asthma Symptom Total Score | Asthma Nighttime Symptom Score | -0.392 score on a scale | Standard Deviation 0.775 |
| Ciclesonide 40 µg | Change in Asthma Symptom Total Score | Asthma Daytime Symptom Score (n=304,312,310,146) | -0.529 score on a scale | Standard Deviation 0.682 |
| Ciclesonide 80 µg | Change in Asthma Symptom Total Score | Asthma Total Symptom Score (n=304,312,310,146) | -0.983 score on a scale | Standard Deviation 1.209 |
| Ciclesonide 80 µg | Change in Asthma Symptom Total Score | Asthma Nighttime Symptom Score | -0.435 score on a scale | Standard Deviation 0.672 |
| Ciclesonide 80 µg | Change in Asthma Symptom Total Score | Asthma Daytime Symptom Score (n=304,312,310,146) | -0.553 score on a scale | Standard Deviation 0.721 |
| Ciclesonide 160 µg | Change in Asthma Symptom Total Score | Asthma Daytime Symptom Score (n=304,312,310,146) | -0.517 score on a scale | Standard Deviation 0.662 |
| Ciclesonide 160 µg | Change in Asthma Symptom Total Score | Asthma Total Symptom Score (n=304,312,310,146) | -0.879 score on a scale | Standard Deviation 1.27 |
| Ciclesonide 160 µg | Change in Asthma Symptom Total Score | Asthma Nighttime Symptom Score | -0.350 score on a scale | Standard Deviation 0.791 |
| Placebo | Change in Asthma Symptom Total Score | Asthma Total Symptom Score (n=304,312,310,146) | -0.572 score on a scale | Standard Deviation 1.483 |
| Placebo | Change in Asthma Symptom Total Score | Asthma Nighttime Symptom Score | -0.233 score on a scale | Standard Deviation 0.858 |
| Placebo | Change in Asthma Symptom Total Score | Asthma Daytime Symptom Score (n=304,312,310,146) | -0.354 score on a scale | Standard Deviation 0.801 |
Secondary
Change in Use of Rescue Medications
The daily use of rescue medication (salbutamol) was recorded in the electronic diary in the morning and the evening. A negative change from Baseline indicates improvement.
Time frame: Baseline and Week 12
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis. Last Observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ciclesonide 40 µg | Change in Use of Rescue Medications | -0.872 puffs/day | Standard Deviation 1.634 |
| Ciclesonide 80 µg | Change in Use of Rescue Medications | -0.999 puffs/day | Standard Deviation 1.523 |
| Ciclesonide 160 µg | Change in Use of Rescue Medications | -0.886 puffs/day | Standard Deviation 1.771 |
| Placebo | Change in Use of Rescue Medications | -0.527 puffs/day | Standard Deviation 1.931 |
Secondary
Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication and Morning PEF
Control of asthma was evaluated on a daily basis (24 hours) using the following variables: asthma symptoms, use of rescue medication, and morning (am) PEF. The median percentage of days with asthma control is presented.
Time frame: 28 days prior to last visit (Up to 12 Weeks)
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ciclesonide 40 µg | Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication and Morning PEF | 8.33 percentage of days |
| Ciclesonide 80 µg | Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication and Morning PEF | 13.64 percentage of days |
| Ciclesonide 160 µg | Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication and Morning PEF | 13.04 percentage of days |
| Placebo | Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication and Morning PEF | 0.0 percentage of days |
Secondary
Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication, Morning PEF and PEF Fluctuation
Control of asthma was evaluated on a daily basis (24 hours) using the following variables: asthma symptoms, use of rescue medication, morning (am) PEF and PEF fluctuation. The median percentage of days with asthma control is presented.
Time frame: 28 days prior to last visit (Up to 12 Weeks)
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ciclesonide 40 µg | Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication, Morning PEF and PEF Fluctuation | 7.14 percentage of days |
| Ciclesonide 80 µg | Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication, Morning PEF and PEF Fluctuation | 10.53 percentage of days |
| Ciclesonide 160 µg | Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication, Morning PEF and PEF Fluctuation | 6.67 percentage of days |
| Placebo | Percentage of Days With Asthma Control Based on Symptoms, Use of Rescue Medication, Morning PEF and PEF Fluctuation | 0.0 percentage of days |
p-value: 0.001Wilcoxon (Mann-Whitney)
p-value: 0.0006Wilcoxon (Mann-Whitney)
p-value: 0.0002Wilcoxon (Mann-Whitney)
Secondary
Time to First Event of Lack of Efficacy (LOE) by Week 12
Kaplan Meier Estimates of the probability of not experiencing LOE by Week 12 was measured. LOE was reached if any of the following criteria occurred during the treatment period: • asthma exacerbation (a worsening of asthma symptoms requiring a change in medication; • nocturnal awakenings due to asthma on any 4 or more nights during any 7-consecutive-day period; • use of more than 8 puffs/day of salbutamol on any 4 or more days during any 7-consecutive-day period; • decrease in morning PEF to \<80% of randomization value on any 4 consecutive days during the treatment period.
Time frame: 12 weeks
Population: Participants from the Intent-to-treat population, all randomized participants who received at least one dose of study drug based on the study drug they were randomized to receive, with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ciclesonide 40 µg | Time to First Event of Lack of Efficacy (LOE) by Week 12 | 72.8 Percent |
| Ciclesonide 80 µg | Time to First Event of Lack of Efficacy (LOE) by Week 12 | 74.5 Percent |
| Ciclesonide 160 µg | Time to First Event of Lack of Efficacy (LOE) by Week 12 | 73.2 Percent |
| Placebo | Time to First Event of Lack of Efficacy (LOE) by Week 12 | 66.9 Percent |
p-value: 0.1362Log Rank
p-value: 0.0891Log Rank
p-value: 0.1574Log Rank