Steady-State Pharmacokinetic Properties of TNX-102 SL, a Sublingual Tablet Formulation of Cyclobenzaprine Hydrochloride (HCl), With Daily Dosing in Healthy Volunteers: A Randomized, Open-Label Trial

Abstract

This single-center, open-label, randomized, multiple-dose, pharmacokinetic bridging study was conducted to compare systemic exposure (AUC and Cmax) of a sublingual tablet formulation of cyclobenzaprine hydrochloride (TNX-102 SL, approved as TONMYA) at steady-state with that of an approved reference product, an oral, extended-release (ER) capsule formulation, supporting development under the 505(b)(2) regulatory pathway. Healthy adults (N = 60) were randomly assigned 1:1 to receive two sublingual 2.8-mg tablets or one oral ER 30-mg capsule once daily for 20 days. At steady state, 2 sublingual 2.8 mg tablets provided lower exposure to cyclobenzaprine and norcyclobenzaprine compared with one oral 30-mg ER capsule. However, when exposures were normalized by dose, cyclobenzaprine AUC0-24 and Cmax were higher on both Day 1 and Day 20 with two sublingual tablets versus one oral ER capsule, supporting higher bioavailability of the sublingual tablet formulation. For Day 20, the dose-normalized ratios (two sublingual tablets: one oral ER capsule) for AUC0-τ ss and Cmax ss were 140% and 152%, respectively. Sublingual tablets and oral ER capsules had comparable metabolic profiles of Phase I and II metabolites in plasma over 20 days, with no unique metabolites by the sublingual route. Sublingual cyclobenzaprine HCl tablets were generally safe and well-tolerated.