Public Assessment Report for paediatric studies submitted in ...

More documents

Recommendations

Info

Due to the inability of 4 and 5-year olds to always perform the spirometry maneuver adequately, FEV1 data, if collected, was not analysed in these patients. PERF data was analysed for all patients 4-11 years old and FEV1 data was analyzed for all patients 6-11 years old. Using a paired t-test and a significance level of 0.05, 60 patients would provide at least 80% power in detecting a difference of 6.1% predicted FEV1 for any pairwise treatment comparison. This sample size would also provide at least 80% power to show a difference of 9,2% in percent of predicted PERF. The primary efficacy endpoints represented the peak effect, measured as a change from baseline in maximum above-baseline percent predicted FEV1 value (for patients aged 6-11) and percent of predicted PEFR value (for patients aged 4-11) observed within 30 minutes of dosing. Other measures of efficacy included some summary measures of serial FEV1 and PEFR (area under the curve, repeated measures [average of 6-hour serial measurements] and weighted average), functions of serial FEV1 and PEFR, and frequency of asthma exacerbations. The primary efficacy measures were assessed via covariance analysis with the percent of predicted same-day baseline as a covariate. The model included terms for treatment, patients within investigator, period, previous treatment, baseline covariate and patient. Results Safety results: Overall, both albuterol DISKUS and albuterol MDI were well tolerated. Adverse events occurred in < 5% of patients having undergone all treatments; no significant differences between doses or formulations or placebo were observed. None of the adverse events were thought by the investigator to be likely, probably, or almost certainly drug-related. None of the vital sign results demonstrated a safety concern. There were no deaths reported during the study. There was one serious adverse event, which was an asthma exacerbation requiring hospitalisation, but was consideredunrelated to study drug. Efficacy results All albuterol treatments were significantly greater than placebo (p≤0.001) based on the peak effect within 30 minutes of dosing of change from same-day baseline in percent predicted PEFR. The peak within 30 minutes of dosing of change from baseline in percent predicted PEFR was similar for albuterol DISKUS (16,0 and 16,1 percent predicted for 200 mcg and 400 mcg doses, respectively) and showed slight improvement for albuterol MDI 400 mcg (17.9 percent predicted) compared to 100 mcg and 200 mcg doses (14.5 and 13.8 percent predicted, respectively). A significant difference was seen in both percent predicted and change from baseline in percent predicted PEFR for albuterol MDI 400 mcg versus 100 mcg (p=0.002 and 0.015 respectively) and 400 mcg versus 200 mcg (p≤0.001 and p=0.003, respectively). Albuterol DISKUS 200 mcg and 400 mcg were not significantly different from each other. All albuterol treatments were significantly greater than placebo (p≤0.001) based on the peak effect within 30 minutes of dosing of change from same-day baseline in percent predicted FEV1. The peak within 30 minutes of dosing of change from baseline in percent predicted PEFR was similar for albuterol DISKUS (15,3 and 15,9 percent predicted for 200 mcg and 400 mcg doses, respectively) and showed slight improvement for albuterol MDI 400 mcg (18.8 percent predicted) compared to 100 mcg and 200 mcg doses (16.7 and 17.1 percent predicted, respectively). There was no significant difference between albuterol MDI 400 mcg and 100 mcg, therefore no other comparisons were considered. Treatment with albuterol DISKUS 200 mcg and albuterol MDI 200 mcg were comparable with respect to the peak within 30 minutes and change from baseline in percent predicted PEFR and FEV1. The percent predicted PEFR change from baseline was slightly greater for albuterol DISKUS 200 mcg compared to albuterol MDI 200 mcg (16.0 and 13.8% predicted, respectively) with a difference of 2.2 % predicted while the change from baseline in percent predicted FEV1 was slightly less for albuterol Salbutamol Final Public Assessment Report RO/W/0001/pdWS/001 Page 16/76
DISKUS 200 mcg compared to albuterol MDI 200 mcg (15.3 and 17.1% predicted, respectively) with a difference of -1.8% predicted. Efficacy results with the 400 mcg doses of albuterol DISKUS and albuterol MDI were relatively similar with respect to the peak effect within 30 minutes and change from baseline in percent of predicted PEFR and FEV1. However, in contrast to results with the 200 mcg doses, where efficacy results favored the DISKUS for PEFR and the MDI for FEV1, results observed with the 400 mcg doses favored the MDI for both PEFR and FEV1. The peak within 30 minutes of dosing of percent change from baseline in PEFR was similar for albuterol DISKUS for 200 mcg and 400 mcg doses and showed slightly greater improvements for albuterol MDI 400 mcg compared to 100 mcg and 200 mcg doses. A higher percentage of patients achieved a ≥ 15% increase from baseline in PEFR in the albuterol treatments compared to placebo throughout the entire 6-hour evaluation. The percent of patients who exhibited a ≥ 15% increase was similar for both doses of albuterol DISKUS. The percent of patients who exhibited a ≥ 15% increase was generally similar for albuterol MDI 100 mcg and 200 mcg doses and higher for albuterol MDI 400 mcg. As we have seen in the case of PEFR, a higher percentage of patients achieved a ≥ 15% increase from baseline in FEV1 with albuterol treatments compared to placebo throughout the entire 6-hour evaluation. The percent of patients who exhibited ≥ 15% increase from baseline in FEV1 was similar for both doses of albuterol DISKUS at most timepoints. A greater percentage of patients achieved ≥ 15% increase with albuterol MDI 400 mcg compared to 100 mcg or 200 mcg doses at most timepoints. For all functions of serial PEFR, the albuterol DISKUS and MDI 200 mcg doses were comparable, including the percent of responders. For FEV1, both devices showed similar median onset of effect, maximum effect and time to maximum effect at the 200 mcg. A greater proportion of patients responded to albuterol MDI compared to albuterol DISKUS at the 200 mcg dose (66 versus 56% respectively), and albuterol MDI 200 mcg appeared slightly better than albuterol DISKUS for offset of effect, duration of effect and AUC (bl). At the 400 mcg dose, a greater proportion of patients were responders with albuterol MDI compared to albuterol DISKUS for both PEFR and FEV1. For functions of PEFR, results with both devices at the 400 mcg dose were relatively similar, although the duration of effect with the DISKUS was slightly longer compared to the MDI (5.8 hours versus 5.18 hours, respectively. Comparison of FEV1 results indicate that albuterol MDI provided a longer duration of effect and median maximum effect compared to albuterol DISKUS, with the other results being comparable. The peak effect within 30 minutes of dosing in percent predicted PEFR or FEV1 for albuterol DISKUS 200 and 400 mcg were comparable without clear evidence of dose response. A dose-response was observed for the peak effect within 30 minutes of dosing for percent predicted PEFR among the three doses of albuterol MDI. Statistically significant differences were seen for the 400 versus 200 mcg ( p
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: central laboratory where this clini
Page 19 and 20: Study period 25 Nov 1996 - 28 May 1
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?