|
Meloxicam is a new nonsterial anti-inflammatory drugs(NSAIDs),
of the enolic acid class. The structure of meloxicam is similar
to piroxicam and tenoxicam. It inhibited prostaglandin
production, like other NSAIDs. Meloxicam has been approved in
Europe, in 1995, for treatment of rheumatic arthritis(RA) and
osteoarthritis(OA). More than 20,000 patients completed clinical
trial, but in Taiwan we have no more information about its
safety profile. So with thistrial, wewant to known the safety
profile of meloxicam in OA patients ofTaiwan.We designed a
prospective, double-blind, double-dummy, randomized, parallel-
group clinical trial, in ten medical centers in Taiwan. The
subjects must be the outpatients of hip or knee OA, over 18
years old and pain on active movement exceeding 35mm by Visual
Analogue Scale(VAS). The patients with active peptic ulcer,
impairment of hepatic and renal function, or hyper- sensitivity
to the trial drugs or other NSAIDs must be excluded. Following
awash-out period for the previously taken NSAIDs of at least
three days,patients were administered either meloxicam 7.5mg
with one diclofenac-placebo once daily or diclofenac slow-
releases 100mg with meloxicam-placebo once dailyaccording to the
randomization scheme for 28 days. Final gloabl assessment of
efficacy, pain on active movement, pain at rest, chang of
arthritis condition,withdrawal due to inadequate efficacy and
improvement of the Western Onterioand McMaster Universities
Osteoarthritis Index were the main efficacy endpoints.Adverse
events in terms of incidence, intensity, causal relationship to
the trial drugs, withdrawals due to adverse events and change in
laboratory valuesand tolerability were the main safety
endpoints. In the inten-to-treat analysis, the frequencies of
AEs in the two treatment groups were compared by calculat-ing
odds rations; GI adverse events were compared by Fisher''s exact
test. Differences of efficacy endpoints on the VAS were analyzed
by two-side t-test.This trial was carried out in accordance with
the Declaration of Helsinki, in accordance with Good Clinical
Practice(GCP) and local laws. This protocol wassubmitted to the
Joint Institution Review oard of Taiwan(JIRB) for ethicalreview,
and reviewed by the Institution Review Board(IRB) of the
hospital.October 1997 throug may 1998, overall of 343 patients
were evaluated for studyeligibility, of which 282 patients
received trial medication (meloxicam140;diclofenac 142). A total
of 236 patients completed the trial (meloxicam 124;diclofenac
112). There was no difference between the two treatment groups
withrespect to the efficacy variables. Withdrawals due to lack
of efficacy occurredrarely in the both group, 1.43% in meloxicam
group, and 3.5% in diclofenacgroup. The number of premature
discontinuations due to AEs was significantlylower in the
meloxicam group (3.57%) than in the diclofenac group
(11.97%)(p=0.009; odds ratio 0.272). Significantly fewer
gastrointestinal adverse eventswere reported in the meloxicam
group (40.0%) compared with the diclofenac (54.23%)(p=0.017;
odds ratio 0.563). The overall clinical laboratory findingsof
meloxicam were comparable to those of diclofenac. SAEs were
reported in zeropatient receiving meloxicam and one patient
receiving diclofenac. AEs of the PUB category (perforation,
ulceration, bleeding) were reported in three patients (all
ulcer) treated with diclofenac and in no patient treated
withmeloxicam. In conclusion, meloxicam 7.5mg once daily was as
effective as diclofenac 100mg s.r. once daily in Taiwan patients
with acute symptomtic osteoarthritis. Meloxicam demonstrated a
more favourable gastrointestinal tolerability compared with
diclofenac s.r.
|