COMPARATIVE EFFICACY OF DICLOFENAC DISPERSIBLE 50 MG AND IBUPROFEN 400 MG IN PATIENTS WITH PRIMARY DYSMENORRHEA - A RANDOMIZED, DOUBLE-BLIND, WITHIN-PATIENT, PLACEBO-CONTROLLED STUDY

Sixty female out-patients suffering from moderate to severe primary dy smenorrhea, aged 14-40 years (mean 27 years), entered this randomized, double-blind, 3-period, within-patient study, evaluating the efficacy and tolerability of diclofenac dispersible 46.5 mg (equivalent to 50 mg of diclofenac sodium), ibuprofen 400 mg and placebo taken up to 4 t imes daily for a maximum of 3 days. Pain relief was evaluated on a ver bal rating scale (0 = none, 1 = slight, 2 = moderate, 3 = considerable , 4 = complete) at 0.5, 1, 2, 3, 4, 5 and 6 hours after the first dose ; the weighted sum of pain relief scores over the 6-hour observation p eriod was also investigated (TOTPAR-6). Pain intensity was assessed on a verbal rating scale (0 = nil, 1 = mild, 2 = moderate, 3 = severe) a t baseline and at the above mentioned time points; the weighted sum of pain intensity differences at each time point was also analyzed (SPID -6). A rescue medication was permitted 1 hour or more after the intake of the test drug: in such cases the last value of pain intensity/reli ef scores was carried forward and used for the analysis. A global eval uation of efficacy and of trial medication as compared to her usual me dication was performed by the patient at the end of each treatment per iod. Finally, adverse experiences were recorded throughout the study p eriod. Analysis of covariance and Koch's adaptation of the Wilcoxon-Ma nn-Whitney rank sum test were used, where appropriate, for statistical analysis. Mean TOTPAR-6 values for diclofenac dispersible, ibuprofen and placebo were 16.5, 17.8 and 14.7, respectively. Diclofenac dispers ible showed a statistically significant superiority over placebo for t his main efficacy variable (p < 0.05), whereas ibuprofen showed only a trend of superiority over placebo (p = 0.076). Mean SPID-6 values for diclofenac dispersible, ibuprofen and placebo were 9, 10.2 and 7.9, r espectively. The contrast between diclofenac dispersible and placebo d id not quite achieve statistical significance (p = 0.08). Ibuprofen di fferentiated statistically from placebo on this measure (p < 0.05). Ov erall efficacy at the end of the treatment period (after multiple dose s) was rated as ''excellent'' or ''good'' by 66% of patients after dic lofenac dispersible, 59% after ibuprofen and 54% after placebo. Diclof enac dispersible was rated superior to the usual treatment by 44.4%, i buprofen by 42.6% and placebo by 34.5% of patients. Eight patients com plained of adverse experiences which were predominantly gastrointestin al, i.e. nausea, abdominal pain, dyspepsia and diarrhea. In 5 patients adverse experiences occurred only during 1 treatment period (4 on dic lofenac dispersible, one on ibuprofen), whereas 3 patients reported ad verse experiences during 2 treatment periods (2 on diclofenac dispersi ble and placebo, 1 on diclofenac dispersible and ibuprofen). The toler ability was assessed as excellent or good by the investigator for 85.7 % of the patients when on diclofenac dispersible, 92.8% when on ibupro fen and 96.5% when on placebo. No significant differences between trea tments were found for the investigator's assessment of overall tolerab ility. Both diclofenac dispersible and ibuprofen have been shown to be effective and well tolerated analgesics for the treatment of moderate to severe primary dysmenorrhea. Additionally, the assay sensitivity o f the trial has been demonstrated (significantly better efficacy of a reference drug, namely ibuprofen, over placebo) with no major differen ces being noted between diclofenac dispersible and ibuprofen with resp ect to the analgesic effect.