Bioequivalence study of a new formulation of paracetamol/ibuprofen during the COVID-19 pandemic

ABSTRACT

Objective: To determine the bioequivalence of two oral formulations of paracetamol 500 mg/ibuprofen 200 mg. Tolerability of both formulations of paracetamol/ ibuprofen were evaluated descriptively. Material and/or methods: Twenty-four healthy volunteers were enrolled at this random, single-dose, crossover, two-period design, open-label, bioequivalence study. After overnight fasting, two formulations (test and reference) of paracetamol/ibuprofen (paracetamol 500 mg/ ibuprofen 200-mg film coated tablets), were administered as a single dose on two treatment days separated by a 72 h (minimum) washout period. After dosing, blood samples were drawn for a period of 12 h. Pharmacokinetic parameters were determined from plasma concentrations for both formulations. The coronavirus disease 2019 (COVID-19) pandemic was declared a public health emergency of international concern by the WHO. Extraordinary safety measures were implemented at different levels that intended to preserve the clinical trial activities as far as possible, protecting the safety and preserving the traceability while no vaccine was available. These measures, locally, consisted of information about the importance of the measures, PCR test for COVID-19 at the screening visit (if IgG serology was positive) and PCR test at every period of admission to Trials Unit, the subject came into the Unit only after a negative result. Results: The highest effort made to assure the safety of participants led to a regular development of the study, with only two cases excluded primarily and one excluded after the first dose administration. Regarding pharmacokinetics, the results found for Paracetamol Ln (Cmax) ng/ml Ratio 92.83% (CI90 83.73%-102.94%);Ln (AUClast) h∗ng/ml Ratio 96.14% (CI90 93.24%-99.13%);for Ibuprofen Ln (Cmax) ng/ml Ratio 93.78% (CI90 85.43-102.96%), Ln (AUClast) h∗ng/ml Ratio 96.06% (CI90 93.75%-98.42%). No drug-related safety concerns appeared. Conclusions: The clinical development of the BE clinical trial was made available by the extraordinary safety measures adopted. The pharmacokinetics results comply with the regulatory requirements for bioequivalence. No significant findings concerning safety were found.