Bioequivalence Trial of Orally Disintegrating Mirtazapine Tablets and Conventional Oral Mirtazapine Tablets in Healthy Volunteers

Abstract

Background: Mirtazapine is a well tolerated and effective antidepressant agent that is currently available as a tablet. Patient compliance with antidepressant treatment that has to be swallowed is very low. Therefore, an orally disintegrating formulation of mirtazapine, which dissolves in the mouth, was devised to improve patient compliance. Objective: To establish the bioequivalence of these two formulations of mirtazapine. Design: Under fasting conditions, participants received in a two-way, single-dose crossover fashion the orally disintegrating formulation of mirtazapine (30mg tablet) [Remeron® Soltab™] and the marketed formulation of mirtazapine (30mg tablet) [Remeron®], separated by a 2-week washout period. Patients and Participants: 40 healthy individuals (20 men, 20 women). Main Outcome Measures and Results: The ratio of geometric means (new formulation: marketed formulation) of pharmacokinetic parameters was 1.072 for the peak concentration of mirtazapine (Cmax) [90% confidence interval (CI) 0.948 to 1.212], 1.103 for the area under the concentration-time curve from zero to the last time-point with a measurable concentration (AUC0-tlast) [90% CI 1.052 to 1.156] and 1.101 for the area under the concentration-time curve from zero to infinity (AUC0-∞) [90% CI 1.049 to 1.156]. The two study formulations were found to be bioequivalent, as all the 90% CIs fell within the acceptance range of 0.80 to 1.25. The adverse events reported were not unexpected and were more likely related to the protocol than to the drug. Somnolence was the most common adverse event, followed by fatigue and dizziness. No clinically significant effects on laboratory safety parameters, vital signs or ECG were observed. Conclusion: A new orally disintegrating formulation of mirtazapine was shown to be bioequivalent to the marketed tablet formulation. This formulation may increase compliance in depressed patients and therefore offer an appropriate alternative for depressed patients currently taking tablets.