Australian public assessment for Ibuprofen - Therapeutic Goods ...

AusPAR Caldolor Ibuprofen Phebra Pty Ltd PM-2010-02393-3-1
Final 2 January 2013
Therapeutic Goods Administration
Finally, while it might possibly be relevant to the use of Caldolor specifically in patients
with malaria, it does not represent a safety issue that would be relevant to the most of the
anticipated usage of Caldolor in Australia.
Sample size
A sample size of 60 patients (30 per treatment) was planned. Based on incomplete data
from a published study, it was hoped that this would be sufficient to detect a betweentreatment
difference in AUC-T0-24 of 12°C×h. An interim analysis was originally planned to
adjust the sample size if necessary but was cancelled prior to unblinding.
Randomisation and blinding methods
Randomisation to Caldolor 400 mg or placebo was on a 1:1 basis. Randomisation and
blinding methods were the same as in CPI-CL-004.
Analysis populations
The Safety Analysis Population (SAP) comprised all randomised patients who received at
least one dose of study medication.
The ITT population included all patients from the safety population who had a baseline
assessment and at least one post-baseline evaluation of the primary endpoint.
The EEP included all patients from the ITT population who had no major protocol
violations with regard to inclusion and exclusion criteria, and who had the required
primary efficacy assessments (temperature measurements in the first 24 h after the start
of study treatment). If 2 or more consecutive temperature measurements were missing in
the first 24 hs, the patient was not eligible for inclusion in the EEP.
Statistical methods
All statistical tests were two-sided, with p-values less than 0.05 for treatment differences
considered significant.
The primary outcome was to be analysed in the ITT population with a supportive analysis
in the EEP. Secondary outcomes were to be analysed only in the EEP. However, the EEP
included all 60 randomised patients, so all outcomes were, in effect, analysed in the ITT
population. Missing temperature values were imputed by linear interpolation or LOCF as
previously described for the primary endpoint. Patients who received rescue treatment
were withdrawn from study medication and temperature measurements subsequent to
recue treatment were substituted with the mean of the treatment group temperature for
that corresponding time point.
Participant flow
The study report did not state the number of prospective participants who were screened.
A total of 60 patients were randomised and progressed as follows:
SAP: 60 patients received study medication and were included in the SAP.
ITT: All 60 patients in the SAP were included in the ITT population.
EEP: The EEP included all 60 patients from the ITT.
A total of 59 patients completed the entire study. One patient in the Caldolor 400 mg
group completed the 5-day treatment period but filed to return from the Day 21 follow-up.
Table 12 summarises the disposition of patients according to treatment group and
analysis population.
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