Asthma
Conditions
Keywords
Asthma, Bronchial
Brief summary
This study will include the patients who are Japanese children with bronchial asthma aged 5 years to 15 years old and have completed the Phase III study (Study code: D5254C00769) at about 29 centres. To investigate the safety of budesonide Turbuhaler® with a daily dose of 100 µg to 800 µg for 54 weeks treatment including the prior 6 weeks Phase III study (Study D5254C00769, NCT00504062) as compared with conventional therapy in Japanese children with bronchial asthma in need of inhaled glucocorticosteroid treatment.
Interventions
DRUGBudesonide
Budesonide Turbuhaler 100 mcg (Pulmicort® Turbuhaler®), 100 - 400 mcg daily
DRUGConventional Asthma Therapy
According to the Japanese Paediatric Guideline for the Treatment and Management of Asthma and at daily dose as judged by the investigator.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Patient who complete preceding the Phase III study and provide a signed written informed consent by patient's legal representative at Visit 1 or 4 weeks prior to Visit 1 of the study. A signed written informed assent should also be obtained from the patients themselves as much as possible * When the investigator will obtain the signed written informed consent of Phase III study (D5254C00769) from patient's legal representative, the investigator will also provide the information of this study
Exclusion criteria
* Respiratory infections that, in the opinion of the investigator(s), may affect the efficacy evaluation e.g., lower airways infection such as pneumonia, infection with no available effective antimicrobial drugs or with deep seated mycosis * Concurrent serious diseases of liver, kidney, heart or other complications which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient's ability to participate in the study. Any clinically relevant abnormal findings in vital sign or physical examination at Visit 1 in this study, which in the opinion of the investigator may put the patient at risk because of his/her participation in the study. * Pregnant or possible pregnancy or planning to become pregnant during the study period * Other subjects who are considered inappropriate to participate in this study judged by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events (AEs). | 54 weeks | AEs were defined as undesirable medical conditions or deteriorations of a pre-existing medical condition following/during exposure. All Serious AEs, AEs leading to withdrawal, Other relevant AE were recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Abnormal Vital Sign Values for the Following Variables: Blood Pressure (Sitting) and Pulse Rate (Sitting), as Judged by the Investigator | 54 weeks | — |
| Number of Patients With Abnormal Plasma Cortisol Values. | 54 weeks | Cut-off value of cortisol is defined as 4 mcg/dL. |
| Height | Baseline and 54 weeks | Height, change from baseline calculated as (height at last visit - height at randomization) |
| Weight | Baseline and 54 weeks | Weight, change from baseline calculated as (weight at last visit - weight at randomization) |
| Morning Peak Expiratory Flow (PEF) Percentage of Predicted Normal | 54 weeks | Change in PEF percent of predicted normal calculated as (PEF percent predicted normal at last visit - PEF percent predicted normal at randomization). |
| Change From Baseline of Respiratory Condition at Asthma Attacks (Daytime) | Baseline and 54 weeks | Change in respiratory condition at asthma attacks (daytime) from baseline to last visit. Scale: 0 - 4. 0 = None. 1 = Mild. 2 = Moderate. 3= Severe. 4 = Respiratory insufficiency |
| Number of Patients With Abnormal Clinical Laboratory Test Values. | 54 weeks | Analysis of haematological, clinical chemistry and urynalysis variables were performed. Haematology variables: erythrocytes, haemoglobin, haematocrit, leucocyte count, leucocyte different count (neutrophils, eosinophils, basophils, lymphocytes, monocytes), platelet count. Clinical chemistry measurements: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, albumin, creatinine,sodium, potassium, total protein, blood urea nitrogen. Urinalysis variables: protein, glucose, urobilinogen, occult. |
| Change From Baseline of Use of Inhaled Short-acting B-2 Agonist (Daytime) | Baseline and 54 weeks | Change in use of inhaled short-acting B-2 agonist (daytime) from baseline calculated as (use of inhaled short-acting B-2 agonist (daytime) at last visit - use of inhaled short-acting B-2 agonist (daytime) at randomization) |
| Change From Baseline of Use of Inhaled Short-acting B-2 Agonist (Night-time) | Baseline and 54 weeks | Change in use of inhaled short-acting B-2 agonist (night-time) from baseline calculated as (use of inhaled short-acting B-2 agonist (night-time) at last visit - use of inhaled short-acting B-2 agonist (night-time) at randomization) |
| Change From Baseline in Disturbance of Daily Activities | Baseline and 54 weeks | Change in disturbance of daily activities from baseline calculated as (disturbance of daily activities at last visit - disturbance of daily activities at randomization). Frequency of disturbance of daily activity was assessed using 3- grade scale (normal, almost able, unable). |
| Change From Baseline in Disturbance of Night-time Sleep | Baseline and 54 weeks | Change in disturbance of night-time sleep from baseline calculated as (disturbances of night-time sleep at last visit - disturbances of night-time sleep at randomization). Frequency of disturbance of night- time sleep was assessed using 3- grade scale (normal, almost able, unable). |
| Forced Expiratory Volume in One Second (FEV1) Percentage of Predicted Normal Change From Baseline | 54 weeks | Forced Expiratory Volume in one second (FEV1) percentage of predicted normal change from baseline calculated as: 100 \* (FEV1 at last visit - FEV1 at randomization)/predicted normal FEV1). |
| Change From Baseline of Respiratory Condition at Asthma Attacks (Nighttime) | Baseline and 54 weeks | Change in respiratory condition at asthma attacks (nighttime) from baseline calculated as (respiratory condition at asthma attacks (nighttime) at last visit - respiratory condition at asthma attacks (night-time) at randomization). Scale: 0 - 4. 0 = None. 1 = Mild. 2 = Moderate. 3= Severe. 4 = Respiratory insufficiency. |
Countries
Japan
Participant flow
Recruitment details
241 Japanese paediatric patients were enrolled into the study
Pre-assignment details
This was an open-label, multi-centre, long-term study in Japanese children with bronchial asthma aged 5 to 15 years, and conducted as an extension of the Phase III study D5254C00769.
Participants by arm
| Arm | Count |
|---|---|
| Budesonide Budesonide Turbuhaler 100 mcg (Pulmicort® Turbuhaler®), 100 - 400 mcg daily. | 121 |
| Conventional Therapy According to the Japanese Paediatric Guideline for the Treatment and Management of Asthma and at daily dose as judged by the investigator. | 120 |
| Total | 241 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-compliance | 2 | 1 |
| Overall Study | Protocol Violation | 4 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Budesonide | Conventional Therapy | Total |
|---|---|---|---|
| Age Continuous | 8.9 Years STANDARD_DEVIATION 2.6 | 8.6 Years STANDARD_DEVIATION 2.3 | 8.8 Years STANDARD_DEVIATION 2.5 |
| Sex: Female, Male Female | 36 Participants | 27 Participants | 63 Participants |
| Sex: Female, Male Male | 85 Participants | 93 Participants | 178 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 100 / 121 | 113 / 120 |
| serious Total, serious adverse events | 10 / 121 | 11 / 120 |
Outcome results
Primary
Number of Patients With Adverse Events (AEs).
AEs were defined as undesirable medical conditions or deteriorations of a pre-existing medical condition following/during exposure. All Serious AEs, AEs leading to withdrawal, Other relevant AE were recorded.
Time frame: 54 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide | Number of Patients With Adverse Events (AEs). | 118 Participants |
| Conventional Therapy | Number of Patients With Adverse Events (AEs). | 116 Participants |
Secondary
Change From Baseline in Disturbance of Daily Activities
Change in disturbance of daily activities from baseline calculated as (disturbance of daily activities at last visit - disturbance of daily activities at randomization). Frequency of disturbance of daily activity was assessed using 3- grade scale (normal, almost able, unable).
Time frame: Baseline and 54 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Change From Baseline in Disturbance of Daily Activities | -0.037 Disturbances per day | Standard Deviation 0.141 |
| Conventional Therapy | Change From Baseline in Disturbance of Daily Activities | -0.017 Disturbances per day | Standard Deviation 0.141 |
Secondary
Change From Baseline in Disturbance of Night-time Sleep
Change in disturbance of night-time sleep from baseline calculated as (disturbances of night-time sleep at last visit - disturbances of night-time sleep at randomization). Frequency of disturbance of night- time sleep was assessed using 3- grade scale (normal, almost able, unable).
Time frame: Baseline and 54 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Change From Baseline in Disturbance of Night-time Sleep | -0.029 Disturbances per night | Standard Deviation 0.134 |
| Conventional Therapy | Change From Baseline in Disturbance of Night-time Sleep | -0.042 Disturbances per night | Standard Deviation 0.132 |
Secondary
Change From Baseline of Respiratory Condition at Asthma Attacks (Daytime)
Change in respiratory condition at asthma attacks (daytime) from baseline to last visit. Scale: 0 - 4. 0 = None. 1 = Mild. 2 = Moderate. 3= Severe. 4 = Respiratory insufficiency
Time frame: Baseline and 54 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Change From Baseline of Respiratory Condition at Asthma Attacks (Daytime) | -0.139 Points on a scale | Standard Deviation 0.334 |
| Conventional Therapy | Change From Baseline of Respiratory Condition at Asthma Attacks (Daytime) | -0.156 Points on a scale | Standard Deviation 0.302 |
Secondary
Change From Baseline of Respiratory Condition at Asthma Attacks (Nighttime)
Change in respiratory condition at asthma attacks (nighttime) from baseline calculated as (respiratory condition at asthma attacks (nighttime) at last visit - respiratory condition at asthma attacks (night-time) at randomization). Scale: 0 - 4. 0 = None. 1 = Mild. 2 = Moderate. 3= Severe. 4 = Respiratory insufficiency.
Time frame: Baseline and 54 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Change From Baseline of Respiratory Condition at Asthma Attacks (Nighttime) | -0.12 Points on a scale | Standard Deviation 0.29 |
| Conventional Therapy | Change From Baseline of Respiratory Condition at Asthma Attacks (Nighttime) | -0.147 Points on a scale | Standard Deviation 0.3 |
Secondary
Change From Baseline of Use of Inhaled Short-acting B-2 Agonist (Daytime)
Change in use of inhaled short-acting B-2 agonist (daytime) from baseline calculated as (use of inhaled short-acting B-2 agonist (daytime) at last visit - use of inhaled short-acting B-2 agonist (daytime) at randomization)
Time frame: Baseline and 54 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Change From Baseline of Use of Inhaled Short-acting B-2 Agonist (Daytime) | -0.21 Puffs per day | Standard Deviation 0.647 |
| Conventional Therapy | Change From Baseline of Use of Inhaled Short-acting B-2 Agonist (Daytime) | -0.242 Puffs per day | Standard Deviation 0.485 |
Secondary
Change From Baseline of Use of Inhaled Short-acting B-2 Agonist (Night-time)
Change in use of inhaled short-acting B-2 agonist (night-time) from baseline calculated as (use of inhaled short-acting B-2 agonist (night-time) at last visit - use of inhaled short-acting B-2 agonist (night-time) at randomization)
Time frame: Baseline and 54 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Change From Baseline of Use of Inhaled Short-acting B-2 Agonist (Night-time) | -0.07 Puffs per day | Standard Deviation 0.415 |
| Conventional Therapy | Change From Baseline of Use of Inhaled Short-acting B-2 Agonist (Night-time) | -0.097 Puffs per day | Standard Deviation 0.368 |
Secondary
Forced Expiratory Volume in One Second (FEV1) Percentage of Predicted Normal Change From Baseline
Forced Expiratory Volume in one second (FEV1) percentage of predicted normal change from baseline calculated as: 100 \* (FEV1 at last visit - FEV1 at randomization)/predicted normal FEV1).
Time frame: 54 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Forced Expiratory Volume in One Second (FEV1) Percentage of Predicted Normal Change From Baseline | 1.5 Percentage | Standard Deviation 15.59 |
| Conventional Therapy | Forced Expiratory Volume in One Second (FEV1) Percentage of Predicted Normal Change From Baseline | 2.31 Percentage | Standard Deviation 16.63 |
Secondary
Height
Height, change from baseline calculated as (height at last visit - height at randomization)
Time frame: Baseline and 54 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Height | 5.34 Centimeters | Standard Deviation 1.99 |
| Conventional Therapy | Height | 6.35 Centimeters | Standard Deviation 1.89 |
Secondary
Morning Peak Expiratory Flow (PEF) Percentage of Predicted Normal
Change in PEF percent of predicted normal calculated as (PEF percent predicted normal at last visit - PEF percent predicted normal at randomization).
Time frame: 54 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Morning Peak Expiratory Flow (PEF) Percentage of Predicted Normal | 9.54 Percentage | Standard Deviation 19.87 |
| Conventional Therapy | Morning Peak Expiratory Flow (PEF) Percentage of Predicted Normal | 5.84 Percentage | Standard Deviation 17.81 |
Secondary
Number of Patients With Abnormal Clinical Laboratory Test Values.
Analysis of haematological, clinical chemistry and urynalysis variables were performed. Haematology variables: erythrocytes, haemoglobin, haematocrit, leucocyte count, leucocyte different count (neutrophils, eosinophils, basophils, lymphocytes, monocytes), platelet count. Clinical chemistry measurements: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, albumin, creatinine,sodium, potassium, total protein, blood urea nitrogen. Urinalysis variables: protein, glucose, urobilinogen, occult.
Time frame: 54 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide | Number of Patients With Abnormal Clinical Laboratory Test Values. | 0 Participants |
| Conventional Therapy | Number of Patients With Abnormal Clinical Laboratory Test Values. | 0 Participants |
Secondary
Number of Patients With Abnormal Plasma Cortisol Values.
Cut-off value of cortisol is defined as 4 mcg/dL.
Time frame: 54 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide | Number of Patients With Abnormal Plasma Cortisol Values. | 20 Participants |
| Conventional Therapy | Number of Patients With Abnormal Plasma Cortisol Values. | 12 Participants |
Secondary
Number of Patients With Abnormal Vital Sign Values for the Following Variables: Blood Pressure (Sitting) and Pulse Rate (Sitting), as Judged by the Investigator
Time frame: 54 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide | Number of Patients With Abnormal Vital Sign Values for the Following Variables: Blood Pressure (Sitting) and Pulse Rate (Sitting), as Judged by the Investigator | 0 Participants |
| Conventional Therapy | Number of Patients With Abnormal Vital Sign Values for the Following Variables: Blood Pressure (Sitting) and Pulse Rate (Sitting), as Judged by the Investigator | 0 Participants |
Secondary
Weight
Weight, change from baseline calculated as (weight at last visit - weight at randomization)
Time frame: Baseline and 54 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Weight | 3.78 kilograms | Standard Deviation 2.77 |
| Conventional Therapy | Weight | 4.39 kilograms | Standard Deviation 3.22 |