Tonix Pharmaceuticals Announces Publication Of The Paper "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," In The Journal 'Clinical Pharmacology In Drug Development'

The publication reports findings from a single-center, randomized, open-label, multiple-dose, parallel-group pharmacokinetic study conducted in 60 healthy adult volunteers. Participants were randomized 1:1 to receive either sublingual cyclobenzaprine HCl 5.6 mg (two 2.8 mg tablets, the FDA approved dose of TONMYA for adults) or oral cyclobenzaprine HCl extended-release (ER) 30 mg capsules (AMRIX®) once daily for 20 consecutive days.

At steady state, exposure to both plasma cyclobenzaprine and norcyclobenzaprine for sublingual tablets (TNX-102 SL) 5.6 mg was substantially lower than that to the comparator listed drug, oral cyclobenzaprine HCl ER 30 mg capsules. Importantly, when exposures were normalized by dose, cyclobenzaprine bioavailability is higher for sublingual tablets at 5.6 mg relative to oral ER 30 mg capsules. Both treatments had comparable metabolic profiles of Phase I and II metabolites in human plasma. These pharmacokinetic results are consistent with the use of sublingual cyclobenzaprine HCl tablets at 5.6 mg to target nonrestorative sleep in fibromyalgia, reduce pain, and potentially improve other symptoms of the condition.

On Day 1, sublingual cyclobenzaprine was detectable within one hour of administration, with median time to peak plasma concentration (tmax) approximately three hours earlier than the oral ER capsule formulation (five vs. eight hours). At steady state on Day 20, the sublingual tmax remained two hours earlier (five vs. seven hours). The sublingual formulation demonstrated markedly higher cyclobenzaprine bioavailability when exposures were normalized by dose.

Daily morning administration of sublingual cyclobenzaprine HCl 5.6 mg over 20 days was generally safe and well tolerated. There were no serious adverse events or treatment discontinuations due to adverse events. All treatment-emergent adverse events were mild or moderate in severity. The most commonly reported adverse events with sublingual tablets occurring at rates higher than oral ER capsules were oral hypoesthesia, abnormal product taste, somnolence, back pain, and fatigue. Since TONMYA is intended for bedtime administration, the effects of somnolence are expected to be an attribute for bedtime dosing when sleepiness effects are beneficial. No metabolites unique to the sublingual route of administration were identified.