TNX-102 SL · program
TNX-102 SL (cyclobenzaprine HCl sublingual) for Acute Stress Disorder
Indications for TNX-102 SL: Fibromyalgia · Approved Acute Stress Disorder · Phase 2 Major depressive disorder · Phase 2 Post-traumatic stress disorder · Discontinued
Investigator-initiated Phase 2 study (OASIS, NCT06636786) of bedtime TNX-102 SL for the early reduction of acute stress reaction (ASR) and acute stress disorder (ASD), and prevention of adverse post-traumatic neuropsychiatric sequelae (including PTSD), in recent trauma survivors. The trial is led by the University of North Carolina (UNC) Institute for Trauma Recovery under a Physician-Initiated IND, funded by a ~$3 million U.S. Department of Defense grant, with Tonix Pharmaceuticals supplying study drug (CT.gov-listed collaborator alongside McLean Hospital and Cooper University Health Care). Approximately 180 motor-vehicle-collision survivors are randomized in the emergency department to a two-week course of TNX-102 SL (an initial 2.8 mg half-dose in the ED followed by 5.6 mg nightly for 14 days) versus placebo. Primary endpoint is change in the 14-item Acute Stress Disorder Scale at weeks 1 and 3. The study is recruiting; topline data are expected in the second half of 2026. No FDA expedited designation has been reported for this indication. This program is distinct from, and developmentally separate from, the discontinued TNX-102 SL PTSD-treatment program.
Development timeline
- UpcomingPhase 2 OASIS topline (TNX-102 SL for acute stress reaction/disorder in ED trauma survivors) anticipated in 2H 2026.↗
- First patient dosed in the Phase 2 OASIS study of TNX-102 SL for reduction of acute stress reaction (Tonix press release); topline results expected in 2H 2026.↗
- OASIS Phase 2 study (NCT06636786) opened; CT.gov actual study start date. Investigator-initiated, UNC-led, DoD-funded (~$3M), Tonix supplying drug; ~180 MVC trauma survivors randomized in the ED to a 2-week course of TNX-102 SL vs placebo, primary endpoint change in the 14-item Acute Stress Disorder Scale.
Readouts
- 2H 2026AnticipatedTopline dataNCT06636786
Phase 2 OASIS topline (TNX-102 SL for acute stress reaction/disorder in ED trauma survivors) anticipated in 2H 2026. ↗
Clinical trials in Acute Stress Disorder
NCT06636786Phase 2Recruitingn=180
Prevention/Reduction of ASRs and PTSD to Sustain Civilian Performance With Sublingual Cyclobenzaprine HCl (TNX-102 SL) (OASIS)
pendingprimaryChange in ASD score on the 14-item Acute Stress Disorder Scale at weeks 1 and 3
Primary endpoint of the recruiting Phase 2 OASIS study: change in the 14-item Acute Stress Disorder Scale (ASD score) at weeks 1 and 3 in MVC trauma survivors randomized in the ED to TNX-102 SL (2.8 mg in the ED, then 5.6 mg nightly x14d) vs placebo. No results yet; topline expected 2H 2026.
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| TNX-102 SL (TONMYA) sublingual tabletsublingual transmucosal disintegrating tablet (bypasses hepatic first-pass metabolism, reducing formation of the long-half-life metabolite norcyclobenzaprine) 2.8 mg starting dose (days 1-14); 5.6 mg target dose (two 2.8 mg tablets, day 15+) once daily at bedtime; maximum 5.6 mg/day | Sublingual | Once nightly | t½ 36 h · Tmax 4.3 h |
Mechanism of action
Cyclobenzaprine is a multifunctional, centrally acting antagonist at several aminergic GPCRs. Reported high-affinity radioligand-binding antagonism at histamine H1 (Ki ~1.3 nM), serotonin 5-HT2A (Ki ~5.2 nM), alpha-1A adrenoceptor (Ki ~5.6 nM) and muscarinic M1 (Ki ~7.9 nM) receptors. In PTSD the therapeutic hypothesis is that bedtime H1/5-HT2A/alpha-1 antagonism improves sleep quality and reduces hyperarousal, with potential disease-modifying effects on sleep-dependent trauma processing. The sublingual formulation is designed to limit the long-lived active metabolite norcyclobenzaprine.
| Target | Action | Affinity |
|---|---|---|
| H1 receptorprimaryHRH1 | Antagonist | Ki 1.3 nMⓘ |
| 5-HT2AHTR2A | Antagonist | Ki 5.2 nMⓘ |
| alpha-1A adrenoceptorADRA1A | Antagonist | Ki 5.6 nMⓘ |
| M1CHRM1 | Antagonist | Ki 7.9 nMⓘ |
← Full TNX-102 SL compound page (identity, identifiers, all indications)
Sources
- Cyclobenzaprine and Its Major Metabolite Norcyclobenzaprine Are Potent Antagonists of Human 5-HT2A, H1 and alpha-Adrenergic Receptors (Daugherty, Gershell, Lederman) — ACR/ARHP Annual Meeting (American College of Rheumatology), 2012
- OASIS: Prevention/Reduction of ASRs and PTSD to Sustain Civilian Performance With Sublingual Cyclobenzaprine HCl (TNX-102 SL) (NCT06636786) — ClinicalTrials.gov
- The Skeletal Muscle Relaxer Cyclobenzaprine Is a Potent Non-Competitive Antagonist of Histamine H1 Receptors — Journal of Pharmacology and Experimental Therapeutics (JPET), 2024
- Tonix Pharmaceuticals Announces First Patient Dosed in Phase 2 OASIS Study of TNX-102 SL for Reduction of Acute Stress Reaction — Tonix Pharmaceuticals / IR (21 May 2025)
- TONMYA (cyclobenzaprine hydrochloride sublingual tablets) FDA Prescribing Information — DailyMed / U.S. FDA