Dose response and safety of cizolirtine citrate (E-4018) in patients with pain following extraction of third molars

The objectives of this study were to determine the dose response and safety of the oral analgesic cizolirtine citrate (E-4018) in patients with postop erative pain after third molar extraction. This was a placebo-controlled, d ouble-blind, randomised, parallel-group study. Doses of E-4018 were 50 mg, 100 mg, or 150 mg. The primary outcome measure of efficacy was patient asse ssment of pain severity determined from serial visual analogue scales (VAS) over a four-hour investigation period. Other efficacy measures included th e number of patients taking escape analgesic and the time before it was tak en, and an overall assessment of pain relief on a four-point categorical sc ale. There was no significant difference between any of the E-4018 treatment gro ups and placebo in terms of the AUC for VAS pain scores over time. The perc entages of patients who rook paracetamol within five hours of their dose we re 100%, 95%, 78% and 82% for the placebo, 50 mg, 100 mg and 150 mg E-4018 groups, respectively. The time to first use of paracetamol was significantl y different for the 100 mg and 150 mg E-4018 groups compared to placebo. Th ere were 17 adverse events, of which five were possibly related to the stud y medication (one in the placebo group and four in the 150 mg E-4018 group) . We conclude that there was a dose-related trend in the percentage of patien ts requiring paracetamol within five hours of their study medication, and i n the percentage of patients that recorded the treatment as providing good or excellent treatment of pain. There was, however, no firm evidence of a d ose-related analgesic effect over the dose range of Cizolirtine chosen for this study. E-4018 was well tolerated in all patients.