Public Assessment Report for paediatric studies submitted in ...

Study population/ sample size - children with a clinical history of reversible airway obstruction
(RAO), stratified into 2 age groups: 6 years or less - 74 children (31%) and 7 years or greater and less than
17 years- 163 (69%).
Treatments - 120 patients received salbutamol CR 4 mg and 117 patients received Salbutamol
standard tablets 2mg. Treatment allocation was randomized in balanced blocks within each of these age
groups. Patients were entered into a 2-week pre trial run-in period and thereafter randomly allocated to
receive one of the treatment regimens for a period of six weeks.
- Group A: Controlled release salbutamol tablets (4 mg salbutamol controlled tablet twice daily
plus one placebo standard 2 mg tablet four times daily)
- Group B: Standard Salbutamol tablets (one placebo controlled tablet twice daily plus one
standard 2 mg salbutamol tablet four times daily)
Endpoints - primary endpoints:
- peak expiratory flow rate (PEER), forced expiratory volume in one second (FEV1) and forced
vital capacity (FVC) were made in those children who were able to perform the spirometry tests reliably.
- second endpoints - vital capacity (VC) and mid expiratory flow rate (FEV50) were
additional optional assessments.
Statistical methods
For respiratory function measurements was applied the standard statistics methods for
evaluation the means values (student’s, t distributions). Clinic lung function measurements were analysed
using regression analysis adjusting for the pre-treatment value and centre.
The mean of the symptom scores for each treatment group were compared following subtraction
of the baseline values, using the non-parametric Mann-Whitney test. The proportion of days with no
symptoms was transformed using the arc-sin transformation (Snedcor and Cochran) and the difference
from baseline values were compared for each treatment group using the standard student’s t test
Safety Assessment - Adverse events were tabulated for the total population as were abnormal
biochemistry measurements. Clinical relevant changes in biochemistry between the start and end of trial
were identified
Results
Efficacy
Baseline lung function and percentage reversibility of the two treatments group at the start of the
study were seen to be similar within each age group for the efficacy population. The CR tablets and
standard tablets were similarly efficacious in maintaining lung function in the 2, 4, 6 week population
(p>0.05).
No clinically significant differences between the treatments were identified with respect to
effects on lung function parameters (FEV1, FVC, PEFR, FE50, VC) for both age groups. In both young
children and the older children compliance was better in the salbutamol CR group.
No significant difference was identified between treatment in the change of symptoms scores
and symptom free days over the study period. (p>0.05).
For the children of 6 years or less 79% of the parents in the salbutamol CR group assessed the
treatment to be effective or very effective as compared to 67% of the parents in the standard tablets group.
For the children of 7 years and over 75% of the parents in the salbutamol CR group assessed the treatment
to be effective or very effective, as compared to 61% of the parents in the standard tablet group
Safety
Adverse events were determined from the total population receiving treatment within each age
group.
No difference between the two treatments were identified either in total numbers of adverse
events or in their severity.
Adverse events are divided into recognized pharmacological effects of salbutamol (tremor,
palpitation, muscle cramps) and non – specific but possibly drug related (headache, hyper-activity and
sleep disturbance) and the remainder which probably not drug related. About 50% of the adverse events
Salbutamol Final Public Assessment Report
RO/W/0001/pdWS/001
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