Asthma
Conditions
Keywords
Bronchial Asthma
Brief summary
Primary objective: To demonstrate the efficacy of ciclesonide, compared to placebo, at 80 μg twice daily (BID) or 40 μg BID for 12 weeks in patients with persistent asthma. Secondary objective: To assess the safety and tolerability of ciclesonide.
Interventions
DRUGCiclesonide
Ciclesonide MDI 40 µg BID over twelve weeks
DRUGPlacebo
Placebo MDI over twelve weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
4 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* History of persistent bronchial asthma for at least 3 months prior to screening; * For patients with persistent bronchial asthma and being treated with a controller therapy: Documented use of an inhaled steroid or Singulair® 5mg once daily; * For patients with persistent bronchial asthma and not being treated with controller therapy: Patients may have documented use of a reliever therapy such as albuterol/salbutamol or may be untreated; * Morning Peak Expiratory Flow (AM PEF) of ≤90% of predicted values from the in-clinic spirometry after a 6 hour withhold of albuterol/salbutamol; * Only patients aged between 6 to \<12 years must have a forced expiratory volume in one second (FEV1) of ≥50% to ≤85% of predicted normal after a 6 hour withhold of albuterol/salbutamol
Exclusion criteria
* Nocturnal awakenings for asthma which require treatment with albuterol/salbutamol for 4 or more nights out of the last 7 days of the screening period; * Use of more than 8 puffs/day of albuterol/salbutamol on 3 or more consecutive days within the last 7 * Upper or lower respiratory tract infection within 4 weeks prior to screening and during screening period; * History of life-threatening asthma, including a history of significant hypercarbia (pCO2 \>45 mmHg), prior intubation, respiratory arrest, or seizures as a result of an exacerbation of asthma; * More than 3 in-patient hospitalization or emergency care visits due to asthma exacerbations in the year prior to screening; * Use of injectable or oral corticosteroids within one month prior to screening, or more than 3 bursts) within 6 months prior to screening;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 12. | Baseline and Week 12 | Change in FEV1 (Percent of predicted) from baseline to week 12. FEV1 was measured only in children between 6 to \<12 years only. Least Squares Mean were adjusted for Baseline FEV1, age \[yrs\], pooled center, previous corticosteroid therapy and holding chamber. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Daily Asthma Symptom Score at Week 12. | Baseline and Week 12 | Change in total daily asthma symptom score from baseline to week 12. 5-Point, ordinal scale specifying patient's experience of symptoms during day and night from 0 (no symptoms) to 4 (symptoms that prevent the patient from engaging in daily activities or sleep) |
| Change From Baseline in Use of Albuterol/Salbutamol at Week 12. | Baseline and Week 12 | Change in albuterol/salbutamol use from baseline to week 12 |
Countries
Hungary, Mexico, Poland, Russia, South Africa, United States
Participant flow
Recruitment details
Screening period 7-14 days, randomization with subsequent treatment period over 12 weeks
Pre-assignment details
The number of subjects in section Participant Flow is related to the number of randomized subjects (= subject who were eligible for treatment period). This number is different to the number of subjects of the Intention to Treat (ITT) population in Outcome Measures. The statistical analyses of the Outcome Measures is related to the ITT population.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Metered Dose Inhaler (MDI) Placebo MDI over twelve weeks (ITT population) | 163 |
| Ciclesonide MDI 40 µg BID Ciclesonide MDI 40 µg BID over twelve weeks (ITT population) | 166 |
| Ciclesonide MDI 80 µg BID Ciclesonide MDI 80 µg BID over twelve weeks (ITT population) | 172 |
| Total | 501 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 17 | 7 | 8 |
| Overall Study | Lack of Efficacy | 8 | 5 | 3 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 |
| Overall Study | Other | 3 | 4 | 1 |
| Overall Study | Parent/legal guardian withdrawal | 1 | 2 | 1 |
| Overall Study | Protocol Violation | 1 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo Metered Dose Inhaler (MDI) | Ciclesonide MDI 40 µg BID | Ciclesonide MDI 80 µg BID |
|---|---|---|---|---|
| Age, Customized Aged 4 to <6 years | 82 participants | 27 participants | 28 participants | 27 participants |
| Age, Customized Aged 6 to <12 years | 419 participants | 136 participants | 138 participants | 145 participants |
| Gender Female | 204 Participants | 59 Participants | 70 Participants | 75 Participants |
| Gender Male | 297 Participants | 104 Participants | 96 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 53 / 172 | 38 / 174 | 28 / 175 |
| serious Total, serious adverse events | 1 / 172 | 1 / 174 | 4 / 175 |
Outcome results
Primary
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 12.
Change in FEV1 (Percent of predicted) from baseline to week 12. FEV1 was measured only in children between 6 to \<12 years only. Least Squares Mean were adjusted for Baseline FEV1, age \[yrs\], pooled center, previous corticosteroid therapy and holding chamber.
Time frame: Baseline and Week 12
Population: Analyses are based on children of the ITT population. It includes all randomized patients who have a baseline and a valid post-randomization lung function measurement. The primary analysis was restricted to an age range between 6 and \<12 years.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Metered Dose Inhaler (MDI) | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 12. | 5.2 Percent of predicted FEV1 | Standard Error 1.06 |
| Ciclesonide MDI 40 µg BID | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 12. | 5.3 Percent of predicted FEV1 | Standard Error 1.06 |
| Ciclesonide MDI 80 µg BID | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 12. | 7.7 Percent of predicted FEV1 | Standard Error 1.06 |
Comparison: This is an analysis of the change from baseline to week 12 or last visit. In this pairwise comparison Ciclesonide was compared with Placebo by testing the average effect of Ciclesonide 40 and Ciclesonide 80 versus Placebo. As statistical test a t-test was used to compare the corresponding least-square means of both treatment groups.p-value: 0.2696ANCOVA
Comparison: This is an analysis of the change from baseline to week 12 or last visit. A t-test was used to compare the least-square means of Ciclesonide 80 versus Placebo.p-value: 0.0703ANCOVA
Comparison: This is an analysis of the change from baseline to week 12 or last visit. As statistical test a t-test was used to compare the corresponding least-square means of Ciclesonide 40 versus Placebo.p-value: 0.9146ANCOVA
Secondary
Change From Baseline in Total Daily Asthma Symptom Score at Week 12.
Change in total daily asthma symptom score from baseline to week 12. 5-Point, ordinal scale specifying patient's experience of symptoms during day and night from 0 (no symptoms) to 4 (symptoms that prevent the patient from engaging in daily activities or sleep)
Time frame: Baseline and Week 12
Population: Analyses are based on children of the ITT population. It includes all randomized patients who have a baseline and a valid post-randomization lung function measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Metered Dose Inhaler (MDI) | Change From Baseline in Total Daily Asthma Symptom Score at Week 12. | -0.96 Scores on a scale | Standard Error 0.08 |
| Ciclesonide MDI 40 µg BID | Change From Baseline in Total Daily Asthma Symptom Score at Week 12. | -1.13 Scores on a scale | Standard Error 0.08 |
| Ciclesonide MDI 80 µg BID | Change From Baseline in Total Daily Asthma Symptom Score at Week 12. | -0.99 Scores on a scale | Standard Error 0.08 |
Secondary
Change From Baseline in Use of Albuterol/Salbutamol at Week 12.
Change in albuterol/salbutamol use from baseline to week 12
Time frame: Baseline and Week 12
Population: Analyses are based on children of the ITT population. It includes all randomized patients who have a baseline and a valid post-randomization lung function measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Metered Dose Inhaler (MDI) | Change From Baseline in Use of Albuterol/Salbutamol at Week 12. | -0.59 Puffs per day | Standard Error 0.08 |
| Ciclesonide MDI 40 µg BID | Change From Baseline in Use of Albuterol/Salbutamol at Week 12. | -0.87 Puffs per day | Standard Error 0.08 |
| Ciclesonide MDI 80 µg BID | Change From Baseline in Use of Albuterol/Salbutamol at Week 12. | -0.93 Puffs per day | Standard Error 0.08 |