Background and aims This is a prospective, single centre, two-part, three doses study. Part 1 is a Phase I, three cohorts, dose-ascending, open-label, safety study. Part 2 is a Phase II, randomised, parallel-group, double-blind, placebo-controlled, exploratory efficacy and safety study.
Methods Part 1 was designed with a dose-ascending design evaluating the safety of the 3 dose levels, enrolling 3 patients for each dose level (1 patient at a time, with the evaluation of each single patient in each cohort followed by the evaluation of each dose level cohort). The second and third cohorts were studied only after full safety assessments of the previous cohort(s).The objective of Part 1 was to evaluate and confirm the safety of the 3 doses of paracetamol 3% solution (D1: 60 mg, D2: 90 mg and D3: 120 mg) administered by intrathecal injection before the injection of hyperbaric bupivacaine HCl 0.5% (patient height ≤160 cm: 12.5 mg; patient height >160 cm: 15 mg).
Results Six adverse events (AEs) were experienced by 4 of the 9 patients enrolled. None of the 6 reported AEs was deemed related to the investigational medicinal product. All AEs were mild or moderate and resolved immediately. There were no severe AEs. No patient withdrew from the study for an AE.
Conclusions The present safety report shows the safety results obtained in the 3 cohorts of Part 1: intrathecal injection of paracetamol 3% is safe. Part 2, evaluating the efficacy of the treatment in reducing post-operative pain will be completed soon.