Effect of High Dose Ciclesonide on Asthma Control
- Registration Number
- NCT01455194
- Lead Sponsor
- AstraZeneca
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 520
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CIC 160 Ciclesonide Two puffs of 40 mcg ciclesonide inhaled in the morning and the evening (corresponding to a total daily dose of 160 mcg) CIC 320 Ciclesonide Two puffs of 80 mcg ciclesonide inhaled in the morning and the evening (corresponding to a total daily dose of 320 mcg) CIC 640 Ciclesonide Two puffs of 160 mcg ciclesonide inhaled in the morning and the evening (corresponding to a total daily dose of 640 mcg)
- Primary Outcome Measures
Name Time Method Change From Baseline in ACQ Score to Tlast Week 52 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.
Asthma Control Questionnaire (ACQ) Score at Baseline 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.
- Secondary Outcome Measures
Name Time Method Time Course of ACQ Baseline, Week 52 (Treatment period) 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.
Number of Participants Reporting Time to First Well-Controlled Asthma and ACQ Improvement Baseline up to Week 52 (treatment period) 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.
Number of Weeks With Well-controlled Asthma Over the Course of the Study Baseline up to Week 52 (treatment period) 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.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) 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.
Number of Participants Reporting Clinically Significant Change From Baseline in Physical Examination Findings Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) 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.
Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) 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.
Number of Participants With Markedly Abnormal Laboratory Values Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56) 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.
Number of Participants With Well-controlled Asthma and ACQ Improvement at the End of the Study Week 52 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.
Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point Baseline up to Week 52 (treatment period) 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.
Number of Participants With Markedly High Benefits Week 1 up to Week 52 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.
Number of Participants Reporting Time to First Asthma Exacerbation Baseline up to Week 52 (treatment period) 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
Number of Participants Reporting Asthma Exacerbations Rates Baseline up to Week 52 (treatment period) 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.