A Comparative Study of Inhaled Ciclesonide Versus Placebo in Children (6-11 Years) With Asthma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Comparative Study of Inhaled Ciclesonide Versus Placebo in Children With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Ciclesonide
* Drug: Placebo
* Drug: Salbutamol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ciclesonide 40 µg<br>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. | Drug: Ciclesonide<br>* inhaled Ciclesonide<br>Drug: Placebo<br>* Ciclesonide placebo-matching inhaler<br>Drug: Salbutamol<br>* Salbutamol inhalation powder<br>|
| Active Comparator: Ciclesonide 80 µg<br>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. | Drug: Ciclesonide<br>* inhaled Ciclesonide<br>Drug: Placebo<br>* Ciclesonide placebo-matching inhaler<br>Drug: Salbutamol<br>* Salbutamol inhalation powder<br>|
| Active Comparator: Ciclesonide 160 µg<br>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. | Drug: Ciclesonide<br>* inhaled Ciclesonide<br>Drug: Placebo<br>* Ciclesonide placebo-matching inhaler<br>Drug: Salbutamol<br>* Salbutamol inhalation powder<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Ciclesonide placebo-matching inhaler<br>Drug: Salbutamol<br>* Salbutamol inhalation powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 weeks | 
| 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. | 28 days prior to last visit (Up to 12 Weeks) | 
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Weeks 1 thru 12 | 
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Week 12 | 
| 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. | 28 days prior to last visit (Up to 12 Weeks) | 
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Ciclesonide, children