Bioequivalence of 2 Naproxen Sodium Tablet Formulations in Healthy Male and Female Volunteers

Abstract Purpose This current study aimed to assess comparative bioavailability between the Test medicinal product, RB naproxen sodium 220 mg tablets, and a Reference medicinal product, Aleve® naproxen sodium 220 mg, in the fasted state. Methods This was a randomized, single-dose, 2-way crossover, open-label, comparative bioavailability, pharmacokinetic study in 18 healthy male and female subjects with a 5-8-day washout permitted between doses (based on the anticipated minimum washout period for naproxen determined from the known terminal elimination half-life of up to 17 hours). Blood samples were taken periodically over a 72-h period following dosing and analysed for plasma naproxen concentration using a validated liquid-chromatography tandem mass-spectrometry method. Noncompartmental pharmacokinetic analysis was used to derive pharmacokinetic parameters for naproxen; safety and tolerability were evaluated throughout the study. Findings Following a single-dose administration of naproxen sodium tablets (2 × 220 mg), the C max and AUC 0-t (geometric LSmean) for the Test product was 65.88 µg/mL and 893.37 h*µg/mL respectively; and for the Reference product was 64.59 µg/mL and 890.60 h*µg/mL. The geometric LSmean Test/Reference ratio 90% CI for both C max (93.98-110.70) and AUC 0-t (98.04-102.63) was contained entirely within the pre-defined 80.00% - 125.00% lower and upper limits; additionally, there was no statistically significant difference in T max (p=0.9878) following fasted administration of the Test and Reference product. There was 1 treatment emergent adverse event reported during the study; there were no serious adverse events, no suspected unexpected serious adverse events and no clinically significant changes in laboratory safety, vital signs or 12-lead ECG measurements reported. Conclusions This single-dose study found that the Test product (RB naproxen sodium tablets) and Reference product (Aleve® naproxen sodium tablets) met the regulatory criteria for bioequivalence in these fasted male and female volunteers; both Test and Reference products were found to be safe and well tolerated.