Australian public assessment for Ibuprofen - Therapeutic Goods ...

CPI-CL-006
Study design, objectives, location and dates
AusPAR Caldolor Ibuprofen Phebra Pty Ltd PM-2010-02393-3-1
Final 2 January 2013
Therapeutic Goods Administration
CPI-CL-006 was a randomised, double-blind, placebo-controlled trial that evaluated the
efficacy and safety of multiple doses of Caldolor 400 mg for the treatment of fever in
hospitalised adults with uncomplicated falciparum malaria. The study was conducted at a
single centre in Thailand from April to July 2002.
Inclusion and exclusion criteria
CPI-CL-006 enrolled hospitalised adults with uncomplicated falciparum malaria and a
fever >38.0°C (100.4°F), based on the 2 highest temperature measurements at least 1 h
apart during the 12 h prior to the first dose of study medication. Prospective patients were
excluded if they had received an antipyretic drug within the last 8 hs, had a
contraindication or major precaution to NSAID use (such as known NSAID allergy, platelet
abnormalities, bleeding risk, renal impairment), or whose fever was due to certain causes
for which NSAID treatment would not be expected to be useful (neurogenic fever, blood or
drug reaction).
All study participants were to have falciparum malaria. As noted for CPI-CL-004, this
means that the study population does not reflect the likely usage of Caldolor in Australia. It
serves as an adequate model for demonstrating antipyretic efficacy but not for assessing
safety in an Australian context.
Screening temperatures were taken up to 2 h before the first dose of study treatment, and
unlike CPI-CL-004, the protocol did not require patients to be febrile at the time of (or
soon before) the first dose. In actuality, however, all patients had a temperature ≥38.0°C at
the time of the first dose.
The exclusion criteria were almost the same as in CPI-CL-004 and reflect the standard
precautions and contraindications for ibuprofen.
Study treatments
Caldolor 400 mg or placebo were administered IV over 30 minutes, every 6 h for the first 3
days (72 hs) and then 6-hly as required for a further 2 days to treat a fever greater than
38.0°C (100.4°F). Each dose of Caldolor was diluted in 100 mL of normal saline.
The IV catheter used for administration of study medication was flushed with normal
saline before and after each infusion. If a central venous catheter was available, that route
of administration was preferred, however, a peripheral IV line with good blood return was
acceptable.
In addition, standard artemisinin-based combination anti-malarial therapy (ACT) was
initiated once study treatment had commenced and was continued throughout the study.
Antipyretic medications (including aspirin, other NSAIDs and paracetamol) and antipyretic
procedures (including cold packs, cooling blankets and alcohol baths) were not
permitted within 8 h before the start of study medication. Corticosteroids were not
permitted during the study. Once study medication had been commenced, the use of cold
packs, cooling blankets, alcohol baths, or other similar treatments was only permitted as
rescue treatment following treatment failure. Treatment failure was defined as a
temperature >41.1°C (106.0°F) a minimum of 2 h following the first dose of study
medication, or a temperature >39.4°C (103.0°F) a minimum of 2 h after the second or
subsequent doses of study medication.
The study report did not state that concomitant antipyretic medications (as distinct from
physical measures) were prohibited but the listing of concomitant medications shows that
such medications were not given. The use of antimalarial therapy would tend to reduce
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