Florin Constantin Enache
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

A clinical study was performed in order to prove the non-inferiority in relieving headache of a unique dose of treatment using Algopirin®, a fixed combination with acetylsalicylic acid (ASA, aspirine), acetaminophen, caffeine and clorpheniramine a new analgesic combination versus Excedrin®, which contains the same active substances but in much higher doses. Pain intensity was quantified using a Visual Analog Scale (VAS) score which was established by patients on a 1 – 100 points scale, before and 30 min, 60 min, 120 min, 180 min and 240 min after drug intake. The clinical trial was a cross-over study with two periods and two sequences, usual in bioequivalence studies, each subject being its own control. Consequently in this study were applied specific statistical methods for bioequivalence studies. The primary endpoint in the statistical evaluation was the Area Under the Pain Curve (AUC).

For verification of therapeutic equivalence there were applied both parametric (method of confidence intervals) and non-parametric methods (Wilcoxon-Man Whitney two one-sided test for bioequivalence, and confidence interval associated with Wilcoxon signed rank statistic based of Hodges - Lehmann estimator). If the 90 % confidence interval for ratio of means of areas under curve was included in the interval 80 – 125 % the products were considered as therapeutically equivalent. The results of all applied tests indicated a therapeutic equivalence of the formulations though amounts of active substances are much lower in Algopirin®.