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

Résumé fourni par la source

Abstract This single‐center, open‐label, randomized, multiple‐dose, pharmacokinetic bridging study was conducted to compare systemic exposure (AUC and C max ) 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 AUC 0‐24 and C max 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 AUC 0‐τ ss and C max 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.

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