Public Assessment Report for paediatric studies submitted in ...

More documents

Recommendations

Info

were fewer significant differences between the 200 mcg and 400 mcg doses of albuterol MDI and no significant differences between 200 mcg and 400 mcg doses of albuterol DISKUS. The albuterol DISKUS 200 mcg and albuterol MDI 200 mcg comparisons were generally similar for PEFR. There were occasional differences favoring albuterol MDI 200 mcg for FEV1. Assessor’s Comment This report contains an adequate efficacy and safety review of albuterol DISKUS 200 mcg and 400 mcg. Patients were aged between 4 and 11 years. However, no sub-analysis for the paediatric population was provided for patients between 4 and 6 years of age. Therefore this study is of limited value for indication of salbutamol DISKUS for children aged 4-6 years. It is acknowledged that the lower limit for this device (DISKUS) for paediatric use is 6 years. No recommendation for inclusion the age 4-6 years for albuterol DISKUS will be made. Single dose of albuterol DISKUS 200 mcg and 400 mcg induced significant bronchodilatation measured by peak effect within 30 minutes of dosing in change from same-day baseline in percent predicted PEFR and FEV1. There were no significant differences in efficacy between the two doses. No clinically relevant difference in efficacy was observed for treatment with albuterol DISKUS 200 mcg compared to that of albuterol MDI 200 mcg. The occurrence of in-clinic asthma exacerbations was similar across all albuterol treatments. All doses of albuterol MDI also induced significant bronchodilation when compared to placebo. For FEV1, a trend towards dose-response was observed among the doses of albuterol MDI. Albuterol DISKUS 200 mcg induced slightly better bronchodilation to that of albuterol MDI 200 mcg, as assessed by peak effect within 30 minutes in change from baseline in percent predicted PEFR whereas for FEV1, albuterol MDI appeared to provide a slightly greater benefit. Peak change in PEFR within 30 minutes of dosing observed with albuterol DISKUS 200 was slightly greater than that for albuterol MDI 200 mcg, but no statistically significant. Since measurement of PEFR included 4 and 5-year old children, this difference may reflect a more efficient use of the DISKUS than of MDI in younger children. Similar findings for secondary and other efficacy measures have also supported the efficacy of albuterol DISKUS and MDI. All albuterol treatment periods demonstrated efficacy versus placebo through 6 hours following treatment, with the exception of albuterol MDI 100 mcg for which the efficacy was demonstrated for only 4 hours following treatment. Albuterol DISKUS and albuterol MDI treatments were well tolerated during this single-dose study. The safety profile (adverse events and serial vital signs) of the albuterol treatments was comparable to that of placebo. 2.1.2 Pressurized metered dose inhaler (pMDI) Ventolin Evohaler studies in children aged 4 years and over: Study/Protocol Number: SALA 3006 Study title: A Randomized, Double Blind, Parallel Group, Clinical Trial Assessing the Safety and Efficacy of Albuterol 200 mcg (180 mcg ex-actuator) QID in CFC Propellant 11/12 Versus Albuterol 200 mcg (180 mcg ex-actuator) QID in GR 106642X Propellant versus Placebo (GR 106642X) in Paediatric Subjects Aged 4-11 Years with Asthma Salbutamol Final Public Assessment Report RO/W/0001/pdWS/001 Page 18/76
Study period 25 Nov 1996 - 28 May 1997 GSK Study Report Number: Report No. RM1997/00818/00. Methods • Objective – To compare the efficacy and safety of Albuterol 200 mcg in CFC Propellant 11 and 12 (P11/12) given QID to Albuterol 200 mcg in GR106642X Propellant given QID with placebo (GR106642X) via the MDI when administered for 2 weeks in paediatric subjects with asthma. • Study design - Multicenter Study, 10 centres in the USA and 1 centre in Puerto Rico, Phase III • Study population /Sample size – 135 male or premenarchal female patients 4 to 11 years of age, with asthma (ATS definition) requiring chronic pharmacotherapy for at least 6 months prior to screening. Patients have demonstrated a baseline FEV1 of 50 - 80% of predicted normal value and showed reversibility (>15% increase in FEV1 following inhalation of VENTOLIN MDI). • Treatments - During the treatment period, patients were randomized to receive albuterol GR 106642X, 200 mcg via inhalation, albuterol P11/12, 200 mcg via inhalation and placebo GR106642X via inhalation The treatment per age group was as follows: - for 4 – 8 year group – 25 subjects received placebo GR106642X - 26 subjects received albuterol GR106642X - 23 subjects received albuterol P 11/12 - for 9 – 11 year group – 18 subjects received placebo GR106642X - 20 subjects received albuterol GR106642X - 23 subjects received albuterol P 11/12 � Outcomes/endpoints - The primary measures of efficacy were serial measurements of FEV1 (for 6 – 11 years old and those 4-5 years old patient capable of performing spirometry) and PEFR (using the Mini the Wright Peak Flow Metter) for all patients. Secondary measures of efficacy were AM and PM assessment of PEFR, subject rated asthma symptom scores, frequency of night time awakening, use of back-up albuterol and frequency of asthma exacerbation. Safety assessments included clinical adverse events, clinical laboratory tests, vital signs, 12-lead electrocardiograms and physical examinations. FEV1 and PEFR measurements were recorded at each visit as the primary assessments of efficacy. � Statistical Methods Enrollment was planned for 90 evaluable patients (30 completed patients per treatment group).Data from previous studies have suggested that a reasonable assumption for the standard deviation of FEV1 percent of predicted is 12.23%. Using a significance level of 0.05, 30 patients per treatment group provided at least 80% power in detecting a difference of 10% in percent of predicted FEV1 between any treatment groups. Serial PEFR and FEV1 were summarized descriptively by treatment groups at both visits where serial PFTs were performed (Treatment day 1 and Treatment week 2). Change from baseline (either same day baseline or Treatment Day 1 baseline) was calculated for each patient as the PTF at each time point minus the baseline PFT. Percent change was the increase in the PTF as a percentage of the baseline PFT. Predicted PFT was based on the patient’s age, height and sex (Polgar). Repeated Measure Analysis of Variance was used to analyse PEFR for each post-randomization visit where serial PFTs were performed. Repeated measures analysis includes both the equally and unequally weight averages of all measurements. Repeated measures analysis and the individual timepoint analysis, based on percent of predicted PEFR used an Analysis of Covariance F-test with baseline percent of predicted PEFR used an Analysis of Covariance F-test with baseline percent of predicted PEFR as the covariate. Repeated Measures Analysis and the individual timepoint analysis was also based on the change from same day baseline using an Analysis of Variance F-test. Serial FEV1 was analyzed in the same manner. Salbutamol Final Public Assessment Report RO/W/0001/pdWS/001 Page 19/76
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: DISKUS 200 mcg compared to albutero
Page 21 and 22: Investigational products for this s
Page 23 and 24: 180mcg 1 inhalation of 90mcg (Can B
Page 25 and 26: Efficacy results Primary efficacy v
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
show all

Public Assessment Report for paediatric studies submitted in ...

Create successful ePaper yourself

Delete template?

Save as template?