Tonix Pharmaceuticals has reported positive results from a Phase ll, dose-finding clinical trial of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) in military-related post-traumatic stress disorder (PTSD), AtEase study.
PTSD can develop from witnessing or experiencing a traumatic event or ordeal whereby there was a severe threat of or actual occurrence of grave physical harm.
TNX-102 SL is designed to rapidly provide cyclobenzaprine to the bloodstream through sublingual, under the tongue, absorption and to bypass first-pass hepatic metabolism.
The AtEase Study was conducted to evaluate the potential clinical benefit of using TNX-102 SL for treating military-related PTSD at a dose of 2.8mg or 5.6mg.
During the randomised, placebo-controlled study of 231 patients with PTSD at 25 US clinical sites, a bedtime sublingual dose of 2.8mg TNX-102 SL or 5.6mg TNX-102 SL was compared to placebo for the treatment of military-related PTSD.
The retention rate found during the trial was higher than usual for a PTSD clinical trial, since 73% completed the study on placebo, 79% on TNX-102 SL 2.8mg and 84% on TNX-102 SL 5.6mg.
The primary efficacy endpoint was the 12-week mean change from baseline in the severity of PTSD symptoms, as measured by the clinician-administered PTSD Scale for DSM-5 (CAPS-5) between those treated with TNX-102 SL and those receiving placebo.
CAPS-5 is a standardised, structured clinical interview and serves as a standard in research for measuring the symptom severity of PTSD.
The AtEase study was designed to evaluate whether a 2.8mg dose would be an efficacious dose and to provide an opportunity for this study to be one of the major efficacy studies.
However, the 2.8mg dose trended in the direction of a therapeutic effect and it did not reach statistical significance on the primary endpoint.
On the contrary, the 5.6mg dose had a therapeutic effect as assessed by the CAPS-5, which was statistically significant by analysis of covariance, even though this arm of the study was designed to include half the number of patients of the 2.8mg arm.
Tonix noted that the AtEase study successfully demonstrated a dose-response relationship on multiple efficacy and safety measurements.
TNX-102 SL 2.8mg and 5.6mg were well tolerated as evidenced by the high overall completion rate in the active treatment groups, which surpassed the completion rate in the placebo group.
The three treatment arms were well balanced on demographic characteristics.
There were four distinct serious adverse events (SAEs), three in the placebo group, and one (proctitis / peri-rectal abscess) in the TNX-102 SL group, reported to be unrelated to TNX-102 SL.
Tonix Pharmaceuticals president and CEO Dr Seth Lederman said: "TNX-102 SL 5.6mg taken sublingually at bedtime demonstrated efficacy (reduction in CAPS-5 score) and safety for the treatment of military-related PTSD compared to placebo.
"We are pleased to have established a dose-response relationship of TNX-102 SL in this Phase ll PTSD study and identified the 5.6mg dose as appropriate for the Phase lll development.
"We plan to meet with the FDA to discuss the clinical programme for supporting the registration of TNX-102 SL 5.6mg for the treatment of PTSD."