Effect of High Dose Ciclesonide on Asthma Control

Study Overview
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Brief Summary
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The aim of the trial is to investigate asthma control with 160 to 640 mcg ciclesonide/day. Asthma control will be assessed by the Asthma Control Questionnaire (ACQ).

Official Title
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Control of Moderate or Severe Asthma With 160, 320 and 640 mcg Ciclesonide/Day. A One-year Randomised, Double-blind, Multicenter Trial.

Conditions
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Bronchial Asthma

Intervention / Treatment
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* Drug: Ciclesonide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent was provided History of persistent bronchial asthma for at least 6 months Current treatment with an Inhaled Corticosteroid (ICS) at a stable dose in the dose range of 200-1000 μg Fluticasone Propionate (FP)/day or equivalent for a minimum of 12 weeks Good inhalation technique Under the current ICS pre-treatment the ACQ score ranges between ≥ 0.75 and ≥ 2 Exclusion Criteria: Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation Concomitant severe diseases (e.g. malignant diseases during the past 5 years [other than basal or squamous cell carcinoma], hepatitis C, acquired immune deficiency syndrome [AIDS]) Diseases which are contraindications for the use of ICS (e.g. active or inactive pulmonary tuberculosis or relevant fungal, bacterial or viral infections of the lower respiratory tract demanding specific treatment) Use of systemic glucocorticosteroids within 4 weeks (injectable depot steroids 6 weeks) before entry into the baseline period, or more than 3 times during the last 6 months

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CIC 160<br>Two puffs of 40 mcg ciclesonide inhaled in the morning and the evening (corresponding to a total daily dose of 160 mcg) | Drug: Ciclesonide<br>* During the treatment period subjects will inhale two puffs of either 40, 80 or 160 μg ciclesonide in the morning and the evening (corresponding to a total daily dose of 160, 320 or 640 μg)<br>|
| Active Comparator: CIC 320<br>Two puffs of 80 mcg ciclesonide inhaled in the morning and the evening (corresponding to a total daily dose of 320 mcg) | Drug: Ciclesonide<br>* During the treatment period subjects will inhale two puffs of either 40, 80 or 160 μg ciclesonide in the morning and the evening (corresponding to a total daily dose of 160, 320 or 640 μg)<br>|
| Active Comparator: CIC 640<br>Two puffs of 160 mcg ciclesonide inhaled in the morning and the evening (corresponding to a total daily dose of 640 mcg) | Drug: Ciclesonide<br>* During the treatment period subjects will inhale two puffs of either 40, 80 or 160 μg ciclesonide in the morning and the evening (corresponding to a total daily dose of 160, 320 or 640 μg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Control Questionnaire (ACQ) Score at Baseline | The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. | Baseline | 
| Change From Baseline in ACQ Score to Tlast | The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Course of ACQ | The time course of the incidence of a 0.5 points improvement of ACQ score was evaluated. Mean ACQ values over time by treatment group for on-treatment site measurements was assessed. The time course of asthma control (ACQ) was done on a weekly base using home-based and site-based ACQ measurements. The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. | Baseline, Week 52 (Treatment period) | 
| Number of Weeks With Well-controlled Asthma Over the Course of the Study | The number of weeks with well-controlled asthma is defined as the number of weeks that the participant had an ACQ score of 0.75 or lower over the course of the study. The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. | Baseline up to Week 52 (treatment period) | 
| Number of Participants With Well-controlled Asthma and ACQ Improvement at the End of the Study | Well-controlled asthma at the end of the study was defined as a participant with an ACQ score of 0.75 or lower. ACQ improvement was defined as a decrease in ACQ score of at least 0.5. The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. | Week 52 | 
| Number of Participants Reporting Time to First Well-Controlled Asthma and ACQ Improvement | Well-controlled asthma at the end of the study was defined as a participant with an ACQ score of 0.75 or lower. ACQ improvement was defined as a decrease in ACQ score of at least 0.5. The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. | Baseline up to Week 52 (treatment period) | 
| Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | Well-controlled asthma was defined as an ACQ score of equal to or lower than the ACQ cut-off point.The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. It includes 5 questions about symptoms, 1 question about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. | Baseline up to Week 52 (treatment period) | 
| Number of Participants Reporting Time to First Asthma Exacerbation | Asthma exacerbations were defined as a worsening of asthma requiring either treatment with oral (or other systemic) glucocorticosteroids for at least 3 days or hospitalisation or a visit to the emergency room because of asthma. Baseline was defined as the average of the ACQ measurements of the last 2 weeks at site prior to first intake of double-blind study medication | Baseline up to Week 52 (treatment period) | 
| Number of Participants Reporting Asthma Exacerbations Rates | Participants with at least 1 asthma exacerbation in the double-blind treatment period have been reported. As predefined in the protocol, the results for participants with missing data for any category were not included. | Baseline up to Week 52 (treatment period) | 
| Number of Participants With Markedly High Benefits | The analyses was intended to identify participant's subsets that would benefit from dose escalation. This analysis tested the potential factors, including age, sex, pretrial inhaled corticosteroid (ICS) dose category, history of exacerbations, baseline ACQ score, baseline BMI category and smoking status. ACQ includes 5 questions about symptoms, 1 about beta 2 -agonist use and 1 about lung function (FEV1% predicted). Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of 7 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled).Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >=1.5 indicates uncontrolled asthma. As predefined in the protocol, participants with missing data for any category were not included. | Week 1 up to Week 52 | 
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs included both serious AEs and non-serious AEs. Baseline of double-blind treatment period was defined as the average of the measurements of the last 2 weeks at site prior to first intake of double-blind study medication. | Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) | 
| Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs | Vital signs included body temperature, blood pressure (BP) and pulse rate. Normal range for vital signs included: Systolic BP >170 millimeters of mercury (mm Hg) or <85 mm Hg, Diastolic BP >105 mm Hg, resting pulse rate: >120 bpm or <50 bpm, difference in systolic BP at Visit x (increase or decrease) compared with pretreatment >40 mm Hg and difference in pulse rate at Visit x (increase or decrease) compared with pretreatment >30 bpm. Baseline of double-blind treatment period was defined as the average of the measurements of the last 2 weeks at site prior to first intake of double-blind study medication. | Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) | 
| Number of Participants Reporting Clinically Significant Change From Baseline in Physical Examination Findings | Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10). Baseline of double-blind treatment period was defined as the average of the measurements of the last 2 weeks at site prior to first intake of double-blind study medication. | Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) | 
| Number of Participants With Markedly Abnormal Laboratory Values | The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Baseline of double-blind treatment period was defined as the average of the measurements of the last 2 weeks at site prior to first intake of double-blind study medication. | Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ciclesonide, asthma