Bronchial Asthma
Conditions
Keywords
ciclesonide, asthma
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).
Interventions
DRUGCiclesonide
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)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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. |
| 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 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 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 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 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 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 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. |
Countries
Argentina, Brazil, Germany, Israel, Russia
Participant flow
Recruitment details
Participants took part in the study at 5 investigative sites in Argentina, Brazil, Germany, Israel and Russia from 10 November 2011 to 15 August 2014.
Pre-assignment details
Participants with a historical diagnosis of persistent bronchial asthma for at least 6 months,treated with a stable inhaled corticosteroid (ICS)dose for at least 12 weeks were enrolled in a single-blind baseline period receiving 160 microgram(mcg)ciclesonide,then a double-blind treatment period in 1 of 3 treatment arms: ciclesonide 160,320,640 mcg.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Period: Ciclesonide 160 mcg Ciclesonide 80 mcg, MDI, inhalational, twice daily for up to 52 weeks in the double blind treatment period. | 120 |
| Treatment Period: Ciclesonide 320 mcg Ciclesonide 160 mcg, MDI, inhalational, twice daily for up to 52 weeks in the double blind treatment period. | 122 |
| Treatment Period: Ciclesonide 640 mcg Ciclesonide 320 mcg, MDI, inhalational, twice daily for up to 52 weeks in the double blind treatment period. | 125 |
| Total | 367 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 | 3 |
| Overall Study | Deterioration in asthma | 12 | 6 | 14 | 9 |
| Overall Study | Discontinuation criterion fulfilled | 3 | 2 | 0 | 2 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 | 1 |
| Overall Study | Miscellaneous | 4 | 5 | 1 | 4 |
| Overall Study | Pregnancy | 0 | 1 | 1 | 0 |
| Overall Study | Randomisation Failure | 90 | 0 | 0 | 0 |
| Overall Study | Screen Failure | 20 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 21 | 16 | 12 | 9 |
Baseline characteristics
| Characteristic | Treatment Period: Ciclesonide 320 mcg | Treatment Period: Ciclesonide 160 mcg | Total | Treatment Period: Ciclesonide 640 mcg |
|---|---|---|---|---|
| Age, Continuous | 44.7 years STANDARD_DEVIATION 15.6 | 43.2 years STANDARD_DEVIATION 14.86 | 44.4 years STANDARD_DEVIATION 15.57 | 45.3 years STANDARD_DEVIATION 16.22 |
| Baseline asthma control questionnaire (ACQ) | 2.16 units on scale STANDARD_DEVIATION 0.384 | 2.24 units on scale STANDARD_DEVIATION 0.304 | 2.20 units on scale STANDARD_DEVIATION 0.363 | 2.20 units on scale STANDARD_DEVIATION 0.361 |
| Body Mass Index | 28.42 kilogram per meter square (kg/m^2) STANDARD_DEVIATION 6.346 | 27.34 kilogram per meter square (kg/m^2) STANDARD_DEVIATION 5.217 | 27.62 kilogram per meter square (kg/m^2) STANDARD_DEVIATION 5.681 | 27.12 kilogram per meter square (kg/m^2) STANDARD_DEVIATION 5.373 |
| FEV1 reversibility | 23 percent reversibility STANDARD_DEVIATION 17.1 | 25.5 percent reversibility STANDARD_DEVIATION 17.02 | 25.0 percent reversibility STANDARD_DEVIATION 18.41 | 26.5 percent reversibility STANDARD_DEVIATION 20.78 |
| Gender Female | 77 Participants | 72 Participants | 230 Participants | 81 Participants |
| Gender Male | 45 Participants | 48 Participants | 137 Participants | 44 Participants |
| Height | 1.66 meter (m) STANDARD_DEVIATION 0.101 | 1.65 meter (m) STANDARD_DEVIATION 0.093 | 1.65 meter (m) STANDARD_DEVIATION 0.099 | 1.65 meter (m) STANDARD_DEVIATION 0.104 |
| History of exacerbations 0 | 70 participants | 70 participants | 203 participants | 63 participants |
| History of exacerbations 1 | 19 participants | 17 participants | 57 participants | 21 participants |
| History of exacerbations 2-3 | 3 participants | 4 participants | 11 participants | 4 participants |
| History of exacerbations 4+ | 0 participants | 0 participants | 0 participants | 0 participants |
| History of exacerbations Unknown | 30 participants | 29 participants | 96 participants | 37 participants |
| Post-FEV1 | 2.84 L STANDARD_DEVIATION 0.883 | 2.71 L STANDARD_DEVIATION 0.915 | 2.77 L STANDARD_DEVIATION 0.9 | 2.76 L STANDARD_DEVIATION 0.906 |
| Post FEV1 predicted | 90.168 percent of predicted STANDARD_DEVIATION 17.7365 | 84.893 percent of predicted STANDARD_DEVIATION 19.3038 | 87.875 percent of predicted STANDARD_DEVIATION 18.3373 | 88.505 percent of predicted STANDARD_DEVIATION 17.7105 |
| Pre FEV1 predicted | 74.345 percent of predicted STANDARD_DEVIATION 16.7285 | 69.095 percent of predicted STANDARD_DEVIATION 18.4683 | 71.773 percent of predicted STANDARD_DEVIATION 17.9737 | 71.835 percent of predicted STANDARD_DEVIATION 18.4365 |
| Pre-forced expiratory volume in 1 second (FEV1) | 2.35 liter (L) STANDARD_DEVIATION 0.798 | 2.20 liter (L) STANDARD_DEVIATION 0.792 | 2.26 liter (L) STANDARD_DEVIATION 0.797 | 2.23 liter (L) STANDARD_DEVIATION 0.801 |
| Prestudy ICS dose <200(mcg/day) fluticasone propionate(FP)equivalent | 3 participants | 3 participants | 8 participants | 2 participants |
| Prestudy ICS dose High:>500 mcg/dayto=<1000 mcg/day FP equivalent | 7 participants | 5 participants | 23 participants | 11 participants |
| Prestudy ICS dose Low:>=200 mcg/day(=<)250 mcg/day FP equivalent | 37 participants | 40 participants | 119 participants | 42 participants |
| Prestudy ICS dose Medium:>250 mcg/dayto=<500 mcg/day FP equivalent | 75 participants | 72 participants | 217 participants | 70 participants |
| Race/Ethnicity, Customized Black or African American | 5 participants | 6 participants | 15 participants | 4 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 2 participants | 1 participants | 10 participants | 7 participants |
| Race/Ethnicity, Customized White | 115 participants | 113 participants | 342 participants | 114 participants |
| Smoking Status Current | 1 participants | 1 participants | 3 participants | 1 participants |
| Smoking Status Former | 19 participants | 10 participants | 44 participants | 15 participants |
| Smoking Status Never | 102 participants | 109 participants | 320 participants | 109 participants |
| Weight | 77.98 kilograms (kg) STANDARD_DEVIATION 18.993 | 74.59 kilograms (kg) STANDARD_DEVIATION 16.371 | 75.42 kilograms (kg) STANDARD_DEVIATION 16.811 | 73.72 kilograms (kg) STANDARD_DEVIATION 14.66 |
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 | 64 / 520 | 65 / 119 | 65 / 122 | 70 / 126 |
| serious Total, serious adverse events | 1 / 520 | 6 / 119 | 9 / 122 | 0 / 126 |
Outcome results
Primary
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.
Time frame: Baseline
Population: The intent-to-treat (ITT) analysis set included participants having at least 1 postrandomization efficacy assessment.This outcome measure was planned to be analyzed on for the treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Asthma Control Questionnaire (ACQ) Score at Baseline | 2.24 units on a scale | Standard Error 0.031 |
| Treatment Period: Ciclesonide 320 mcg | Asthma Control Questionnaire (ACQ) Score at Baseline | 2.15 units on a scale | Standard Error 0.035 |
| Treatment Period: Ciclesonide 640 mcg | Asthma Control Questionnaire (ACQ) Score at Baseline | 2.19 units on a scale | Standard Error 0.032 |
Primary
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.
Time frame: Week 52
Population: The ITT analysis set included participants having at least 1 postrandomization efficacy assessment.This outcome measure was planned to be analyzed on for the treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Change From Baseline in ACQ Score to Tlast | -0.833 units on a scale | Standard Error 0.1028 |
| Treatment Period: Ciclesonide 320 mcg | Change From Baseline in ACQ Score to Tlast | -0.799 units on a scale | Standard Error 0.1019 |
| Treatment Period: Ciclesonide 640 mcg | Change From Baseline in ACQ Score to Tlast | -0.955 units on a scale | Standard Error 0.0969 |
Comparison: Least square (LS) mean difference were derived from an ANCOVA model with baseline ACQ and age as covariates, and treatment, centre pool, sex, and prestudy ICS dose as factors.p-value: 0.298895% CI: [-0.353, 0.109]ANCOVA
Comparison: Least square (LS) mean difference were derived from an ANCOVA model with baseline ACQ and age as covariates, and treatment, centre pool, sex, and prestudy ICS dose as factors.p-value: 0.774195% CI: [-0.198, 0.266]ANCOVA
Comparison: Least square (LS) mean difference were derived from an ANCOVA model with baseline ACQ and age as covariates, and treatment, centre pool, sex, and prestudy ICS dose as factors.p-value: 0.183595% CI: [-0.387, 0.074]ANCOVA
Secondary
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.
Time frame: Baseline up to Week 52 (treatment period)
Population: The ITT analysis set included participants having at least 1 postrandomization efficacy assessment.This outcome measure was planned to be analyzed on for the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting Asthma Exacerbations Rates | 5 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting Asthma Exacerbations Rates | 10 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting Asthma Exacerbations Rates | 10 participants |
p-value: 0.288Fisher Exact
p-value: 0.2864Fisher Exact
Secondary
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.
Time frame: Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56)
Population: Safety analysis set included all participants who took at least 1 dose of study medication.One participant erroneously randomized into 160 mcg arm, actually received 640 mcg dose.For safety analysis, participants were analyzed based on the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting Clinically Significant Change From Baseline in Physical Examination Findings | 0 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting Clinically Significant Change From Baseline in Physical Examination Findings | 0 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting Clinically Significant Change From Baseline in Physical Examination Findings | 0 participants |
Secondary
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.
Time frame: Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56)
Population: Safety analysis set included all participants who took at least 1 dose of study medication.One participant erroneously randomized into 160 mcg arm, actually received 640 mcg dose.For safety analysis, participants were analyzed based on the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs | 0 participants |
Secondary
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.
Time frame: Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56)
Population: Safety analysis set included all participants who took at least 1 dose of study medication.One participant erroneously randomized into 160 mcg arm, actually received 640 mcg dose.For safety analysis, participants were analyzed based on the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 109 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 85 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 86 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 89 participants |
Secondary
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
Time frame: Baseline up to Week 52 (treatment period)
Population: The ITT analysis set included participants having at least 1 postrandomization efficacy assessment.This outcome measure was planned to be analyzed on for the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting Time to First Asthma Exacerbation | 5 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting Time to First Asthma Exacerbation | 11 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting Time to First Asthma Exacerbation | 10 participants |
p-value: 0.226495% CI: [0.824, 2.267]Log Rank
p-value: 0.137395% CI: [0.789, 5.602]Log Rank
p-value: 0.773295% CI: [0.375, 2.074]Log Rank
Secondary
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.
Time frame: Baseline up to Week 52 (treatment period)
Population: The ITT analysis set included participants having at least 1 postrandomization efficacy assessment.This outcome measure was planned to be analyzed on for the treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma and ACQ Improvement | Well-controlled Asthma | 73 participants |
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma and ACQ Improvement | ACQ Improvement | 112 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma and ACQ Improvement | Well-controlled Asthma | 84 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma and ACQ Improvement | ACQ Improvement | 107 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma and ACQ Improvement | Well-controlled Asthma | 81 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma and ACQ Improvement | ACQ Improvement | 115 participants |
Comparison: Well-controlled Asthmap-value: 0.606295% CI: [0.89, 1.221]Log Rank
Comparison: ACQ Improvementp-value: 0.467495% CI: [0.921, 1.197]Log Rank
Comparison: Well-controlled Asthmap-value: 0.252395% CI: [0.878, 1.642]Log Rank
Comparison: ACQ Improvementp-value: 0.502695% CI: [0.7, 1.191]Log Rank
Comparison: Well-controlled Asthmap-value: 0.489395% CI: [0.661, 1.219]Log Rank
Comparison: ACQ Improvementp-value: 0.219395% CI: [0.906, 1.538]Log Rank
Secondary
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.
Time frame: Baseline up to Week 52 (treatment period)
Population: The ITT analysis set included participants having at least 1 postrandomization efficacy assessment.This outcome measure was planned to be analyzed on for the treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 0.5 | 56 participants |
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 1.0 | 91 participants |
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 1.25 | 99 participants |
| Treatment Period: Ciclesonide 160 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 1.5 | 103 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 1.5 | 105 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 0.5 | 69 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 1.25 | 101 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 1.0 | 95 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 1.5 | 107 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 1.0 | 93 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 1.25 | 101 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants Reporting Time to First Well-Controlled Asthma Measurement by ACQ Cut-Off Point | ACQ cut-off at 0.5 | 63 participants |
Comparison: ACQ cut-off at 0.5p-value: 0.539795% CI: [0.884, 1.266]Log Rank
Comparison: ACQ cut-off at 1.0p-value: 0.945895% CI: [0.87, 1.161]Log Rank
Comparison: ACQ cut-off at 1.25p-value: 0.721395% CI: [0.893, 1.178]Log Rank
Comparison: ACQ cut-off at 1.5p-value: 0.480795% CI: [0.917, 1.202]Log Rank
Comparison: ACQ cut-off at 0.5p-value: 0.11595% CI: [0.934, 1.884]Log Rank
Comparison: ACQ cut-off at 1.0p-value: 0.628195% CI: [0.805, 1.431]Log Rank
Comparison: ACQ cut-off at 1.25p-value: 0.685395% CI: [0.803, 1.397]Log Rank
Comparison: ACQ cut-off at 1.5p-value: 0.699595% CI: [0.804, 1.385]Log Rank
Comparison: ACQ cut-off at 0.5p-value: 0.30895% CI: [0.595, 1.178]Log Rank
Comparison: ACQ cut-off at 1.0p-value: 0.664595% CI: [0.705, 1.25]Log Rank
Comparison: ACQ cut-off at 1.25p-value: 0.956495% CI: [0.753, 1.308]Log Rank
Comparison: ACQ cut-off at 1.5p-value: 0.736795% CI: [0.8, 1.371]Log Rank
Secondary
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.
Time frame: Baseline period (Week -3 up to -1), treatment period (Baseline up to Week 56)
Population: Safety analysis set included all participants who took at least 1 dose of study medication.One participant erroneously randomized into 160 mcg arm, actually received 640 mcg dose.For safety analysis, participants were analyzed based on the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Participants With Markedly Abnormal Laboratory Values | 0 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants With Markedly Abnormal Laboratory Values | 0 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants With Markedly Abnormal Laboratory Values | 0 participants |
Secondary
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.
Time frame: Week 1 up to Week 52
Population: Safety analysis set included all participants who took at least 1 dose of study medication.One participant erroneously randomized into 160 mcg arm, actually received 640 mcg dose.For safety analysis, participants were analyzed based on the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Participants With Markedly High Benefits | 0 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants With Markedly High Benefits | 0 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants With Markedly High Benefits | 0 participants |
Secondary
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.
Time frame: Week 52
Population: The intent-to-treat ITT analysis set included participants having at least 1 postrandomization efficacy assessment.This outcome measure was planned to be analyzed on for the treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Participants With Well-controlled Asthma and ACQ Improvement at the End of the Study | Well-controlled Asthma | 38 participants |
| Treatment Period: Ciclesonide 160 mcg | Number of Participants With Well-controlled Asthma and ACQ Improvement at the End of the Study | ACQ Improvement | 87 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants With Well-controlled Asthma and ACQ Improvement at the End of the Study | Well-controlled Asthma | 45 participants |
| Treatment Period: Ciclesonide 320 mcg | Number of Participants With Well-controlled Asthma and ACQ Improvement at the End of the Study | ACQ Improvement | 81 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants With Well-controlled Asthma and ACQ Improvement at the End of the Study | Well-controlled Asthma | 51 participants |
| Treatment Period: Ciclesonide 640 mcg | Number of Participants With Well-controlled Asthma and ACQ Improvement at the End of the Study | ACQ Improvement | 85 participants |
Comparison: Well-controlled Asthmap-value: 0.4186Fisher Exact
Comparison: Well-controlled Asthmap-value: 0.146Fisher Exact
Comparison: Well-controlled Asthmap-value: 0.6017Fisher Exact
Comparison: ACQ Improvementp-value: 0.3305Fisher Exact
Comparison: ACQ Improvementp-value: 0.486Fisher Exact
Comparison: ACQ Improvementp-value: 0.8922Fisher Exact
Secondary
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.
Time frame: Baseline up to Week 52 (treatment period)
Population: The intent-to-treat ITT analysis set included participants having at least 1 postrandomization efficacy assessment.This outcome measure was planned to be analyzed on for the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Number of Weeks With Well-controlled Asthma Over the Course of the Study | 1211 weeks |
| Treatment Period: Ciclesonide 320 mcg | Number of Weeks With Well-controlled Asthma Over the Course of the Study | 1514 weeks |
| Treatment Period: Ciclesonide 640 mcg | Number of Weeks With Well-controlled Asthma Over the Course of the Study | 1447 weeks |
p-value: 0.846595% CI: [-3, 4]Wilcoxon (Mann-Whitney)
p-value: 0.417595% CI: [-2, 5]Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline, Week 52 (Treatment period)
Population: The ITT analysis set included participants having at least 1 postrandomization efficacy assessment.This outcome measure was planned to be analyzed on for the treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Period: Ciclesonide 160 mcg | Time Course of ACQ | 1.100 Weeks |
| Treatment Period: Ciclesonide 320 mcg | Time Course of ACQ | 1.000 Weeks |
| Treatment Period: Ciclesonide 640 mcg | Time Course of ACQ | 1.000 Weeks |