Public Assessment Report for paediatric studies submitted in ...

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Safety variable including assessment of: � Adverse events � Signs and symptoms of adrenergic stimulation as resulted from the physician’s assessment of tremor and the diary card and the FSII(R) questionnaire, � clinical laboratory assessment � ECG monitoring � vital signs � physical examination � peak expiratory flow in subjects who were capable of performing this maneuver. Statistical methods and determination of sample size: Considering a 10% dropout rate, approximately 75 subjects (25 per treatment group) were planned for enrollment in this study so that a minimum of 22 completed subjects per treatment group could be achieved per regulatory requirement. However the sample size of 22 subjects per treatment arm was not expected to provide enough statistical power to detect any difference between any two-treatment arms. All statistical tests performed assessed similar two-sided hypotheses between treatment groups. The nominal significance level was 0.05. Analysis of daily 24-hour asthma symptom scores, daytime asthma symptom scores, and FSII(R) total scores was performed using ANCOVA. Analysis of the percentage of symptom-free 24-hour days and 24-hour rescue albuterol use was performed using the van Elteren modification of the Wilcoxon rank-sum test. Analysis sets: Total Population - all subjects screened for inclusion in the study. Summaries of subject disposition and reasons for withdrawal prior to randomization were summarized for this population (n=97). Intent-to-Treat (ITT) Population - all subjects who were randomized and received at least one dose of study medication. Analyses of all safety and efficacy data were based on this population (n=77) Screen Failure Population - all subjects screened for inclusion in the study who were discontinued from the study prior to randomization who were not administered study drugs (n=20) Assessor's comment: The patients included in this study are paediatric subjects aged 24 to
Efficacy results Primary efficacy variable Analysis of daily 24-hour asthma symptom scores by holding chamber (Aerochamber Plus or Optichamber) showed similar improvements from baseline in all treatment groups over 4 weeks of treatment. Results were comparable between the holding chambers. Similarly, the analysis of daily 24-hour asthma symptom scores for subjects using concomitant ICS or no concurrent therapy demonstrated similar improvements from baseline in all treatment groups over 4 weeks of treatment Secondary efficacy In the ITT population the daytime asthma symptom scores were similar across the treatment groups at baseline. At endpoint, subjects in the VENTOLIN HFA treated groups experienced fewer daytime asthma symptoms than subjects in the placebo group, however the differences were not significant. At Baseline, the percentage of symptom-free 24-hour days was greater for the placebo group and comparable with the VENTOLIN HFA treated groups. The mean change over the four week treatment period and evaluation at endpoint in percent of symptom-free 24 hour days was greater, although not significant in the two VENTOLIN HFA treated groups. When the weekly percentage of symptom-free 24-hour days was analysed throughout the four weeks of treatment, subjects in the VENTOLIN HFA treated groups demonstrated a greater change from baseline although not significant when compared to placebo At baseline, 24-hour rescue albuterol use was comparable across the treatment groups except for a slightly higher use in the VENTOLIN HFA 180mcg group. At endpoint, subjects in both VENTOLIN HFA groups experienced a slightly greater mean reduction in 24-hour albuterol use; this difference between placebo was greater for subjects in the VENTOLIN HFA 90mcg group, albeit did not achieve statistical significance. The maximum decrease in 24-hour rescue albuterol use ranged between – 1.2 and –2.1 puffs in week 3. Although not significant this decrease was greater in the VENTOLIN HFA treated groups. Other efficacy endpoints In the ITT population, night time asthma symptom scores were similar across the treatment groups at baseline. Subjects in the active groups experienced a reduction in night time asthma symptom scores mostly during the first three weeks of treatment with the maximal decrease in night time symptoms at week 3 (–35.7% change from baseline) for the VENTOLIN HFA 90 mcg group. At endpoint, subjects in all three groups had similar night time symptom scores. The percentage of nights with no awakenings due to asthma for subjects in the VENTOLIN 180mcg group at baseline were slightly lower than the other two groups. Both the VENTOLIN HFA treated groups experienced a greater percentage of nights with no awakenings due to asthma than placebo, which did not change from baseline at endpoint during the 4 weeks of treatment Three subjects using rescue systemic and inhaled corticosteroids during the treatment period, one in the placebo and two in the VENTOLIN HFA 90 mcg group. The subject in the placebo group received systemic corticosteroids and the subjects in the VENTOLIN HFA group received inhaled corticosteroids to treat their exacerbations. Treatment failure was defined as premature discontinuation from the study due to lack of efficacy. The mean time to asthma exacerbation was doubled in the active group. The subject in the placebo group had an exacerbation during the first week of treatment. In the VENTOLIN HFA 90mcg group, one subject had an exacerbation during the second week of treatment while the other experienced an exacerbation during the final week of treatment. Too few subjects had asthma exacerbations to draw any meaningful conclusions regarding time to exacerbation. Salbutamol Final Public Assessment Report RO/W/0001/pdWS/001 Page 25/76
Page 1 and 2: Public Assessment Report for paedia
Page 3 and 4: Pharmacovigilance and PSUR Name: Da
Page 5 and 6: Rapid-acting inhaled β 2 -agonists
Page 7 and 8: The MAHs are requested to submit a
Page 9 and 10: Neonatal onset of symptoms (associa
Page 11 and 12: Study Code: RID/CT/84 (D140/B16); D
Page 13 and 14: of predicted FEV1 to be 12%, the re
Page 15 and 16: central laboratory where this clini
Page 17 and 18: DISKUS 200 mcg compared to albutero
Page 19 and 20: Study period 25 Nov 1996 - 28 May 1
Page 21 and 22: Investigational products for this s
Page 23: 180mcg 1 inhalation of 90mcg (Can B
Page 27 and 28: At Week 4, mean changes from baseli
Page 29 and 30: In the ITT population the daytime a
Page 31 and 32: This study demonstrated similar saf
Page 33 and 34: Protocol deviations were summarised
Page 35 and 36: The overall (based on all evaluable
Page 37 and 38: Three studies regarding the clinica
Page 39 and 40: The improvment in PEF was 51 L. min
Page 41 and 42: eported by the ≤ 6 year age group
Page 43 and 44: suitable for this age because young
Page 45 and 46: In the group treated with salbutamo
Page 47 and 48: common complaints associated with h
Page 49 and 50: although being gradually replaced b
Page 51 and 52: Based on the data submitted, the MA
Page 53 and 54: Inhaled Table 1 Key Differences bet
Page 55 and 56: GDS wording National SmPCs with sig
Page 57 and 58: GDS wording National SmPCs with sig
Page 59 and 60: Question 4 (Rapporteur): With regar
Page 61 and 62: Question 3 In case of divergences b
Page 63 and 64: United Kingdom: Salbulin MDPI Novol
Page 65 and 66: 2. Completely depress the coloured
Page 67 and 68: The harmonised SmPC as outcome of t
Page 69 and 70: Assessment of the Applicant’s res
Page 71 and 72: SALBUTAMOL WZF POLFA 2 mg SALBUTAMO
Page 73 and 74: symptoms. Increased consumption of
Page 75 and 76:
sympathomimetic amines. High doses
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