Tonix Pharmaceuticals Reports Topline Results from Phase 2 AtEase Study of TNX-102

Loading...
Loading...
Tonix Pharmaceuticals Holding Corp.
TNXP
(Tonix), which is developing next-generation medicines for fibromyalgia and post-traumatic stress disorder (PTSD), today announced topline results of the Phase 2 dose-finding clinical study of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) in military-related PTSD (AtEase Study). The goal of the AtEase Study was to evaluate the potential clinical benefit of using TNX-102 SL to treat military-related PTSD at a dose of 2.8 mg or 5.6 mg. In a randomized, placebo-controlled study of 231 patients with PTSD at 25 U.S. clinical sites, a bedtime sublingual dose of 2.8 mg TNX-102 SL (n=90) or 5.6 mg TNX-102 SL (n=49) was compared to placebo (n=92) for the treatment of military-related PTSD. The retention rate was higher than typical for a PTSD clinical trial, since 73% completed the study on placebo, 79% on TNX-102 SL 2.8 mg and 84% on TNX-102 SL 5.6 mg. 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. The CAPS-5 is a standardized structured clinical interview and serves as the gold standard in research for measuring the symptom severity of PTSD. This dose-finding study was designed to evaluate whether a 2.8 mg dose would be an efficacious dose and to provide an opportunity for this study to be one of the pivotal efficacy studies. Although the 2.8 mg dose trended in the direction of a therapeutic effect, it did not reach statistical significance on the primary endpoint. In contrast, the 5.6 mg dose had a therapeutic effect as assessed by the CAPS-5, which was statistically significant by analysis of covariance (ANCOVA) (p-value = 0.038), even though this arm of the study was designed to include half the number of patients of the 2.8 mg arm. The AtEase Study successfully demonstrated a dose-response relationship on multiple efficacy and safety measurements. TNX-102 SL 2.8 mg and 5.6 mg were well tolerated as evidenced by the high overall completion rate in the active treatment groups, which exceeded 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 were in the placebo group, and one (proctitis/peri-rectal abscess), in the TNX-102 SL group, was reported to be unrelated to TNX-102 SL. Seth Lederman, M.D., president and chief executive officer of Tonix, stated, "TNX-102 SL 5.6 mg 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 2 PTSD study and identified the 5.6 mg dose as appropriate for Phase 3 development. We plan to meet with the FDA to discuss the clinical program to support the registration of TNX-102 SL 5.6 mg for the treatment of PTSD." Jonathan R.T. Davidson, M.D., emeritus professor in the Department of Psychiatry and Behavioral Sciences at Duke University Medical Center and former Director of the Anxiety and Traumatic Stress Program, and consultant to Tonix, commented, "There is a continuing need to develop effective and well-tolerated treatments for people whose daily living is impaired by PTSD. I am encouraged by the results that have emerged from this well-designed and carefully executed study and look forward to seeing this drug treatment advance into a registration clinical program." Dr. Lederman added, "In the last decade, there has been little activity in the recruitment of military-related PTSD patients to participate in industry-sponsored, large-scale randomized controlled clinical studies of experimental medicines. We were successful in recruiting a relevant patient population. The AtEase Study evaluated the dose-response relationship of TNX-102 SL and identified the 5.6 mg dose as a clinically effective and well-tolerated dose for registration studies. The results of the AtEase Study not only support the development of TNX-102 SL 5.6 mg towards commercialization, but also help to better understand PTSD, a serious and disabling condition affecting many veterans who have served our country. We are grateful to the participants and their families for supporting this study." Summaries of the preliminary efficacy and safety results are provided in the following tables: Table 1. Preliminary Efficacy of TNX-102 SL in the AtEase Study Assessment Domain Analysis p Values 2.8 mg (N=90) 5.6 mg (N=49) CAPS-5 Total MMRM1 with Multiple Imputation 0.211 0.031* Total ANCOVA 0.090 0.038* Arousal and Reactivity MMRM 0.141 0.048* Sleep E6 Item MMRM 0.185 0.010* Startle E4 Item MMRM 0.336 0.015* CGI-I2 Responder 0.240 0.041* PGIC3 MMRM 0.075 0.035* Sheehan Disability Scale Total MMRM 0.174 0.079 Work/school Item MMRM 0.123 0.050* Social/leisure Item MMRM 0.198 0.031* Family life/home responsibilities Item MMRM 0.375 0.524 1MMRM = Mixed Model Repeated Measures 2CGI-I = Clinician Global Impression-Improvement 3PGIC = Patient Global Impression of Change *p < 0.05 Table 2. Preliminary Adverse Events Reported in > 5% of Subjects in Any Treatment Arm TNX-102 SL Placebo 2.8 mg 5.6 mg Total TNX-102 SL (N=94) (N=93) (N=50) (N=143) Local Administration Site Conditions Hypoaesthesia oral 2 (2.1%) 36 (38.7%) 18 (36.0%) 54 (37.8%) Paraesthesia oral 3 (3.2%) 15 (16.1%) 2 (4.0%) 17 (11.9%) Glossodynia 1 (1.1%) 3 (3.2%) 3 (6.0%) 6 (4.2%) Systemic Adverse Events Somnolence 6 (6.4%) 11 (11.8%) 8 (16.0%) 19 (13.3%) Dry mouth 10 (10.6%) 4 (4.3%) 8 (16.0%) 12 (8.4%) Headache 4 (4.3%) 5 (5.4%) 6 (12.0%) 11 (7.7%) Insomnia 8 (8.5%) 7 (7.5%) 3 (6.0%) 10 (7.0%) Sedation 1 (1.1%) 2 (2.2%) 6 (12.0%) 8 (5.6%) Upper respiratory infection 5 (5.3%) 3 (3.2%) 2 (4.0%) 5 (3.5%) Abnormal dreams 5 (5.3%) 1 (1.1%) 1 (2.0%) 2 (1.4%) Weight increased 5 (5.3%) 1 (1.1%) 1 (2.0%) 2 (1.4%) Tonix's chief medical officer, Gregory Sullivan, M.D., will present topline data from the AtEase Study at the American Society of Clinical Psychopharmacology Annual Meeting to be held in Scottsdale, Arizona on May 31, 2016. TNX-102 SL is an Investigational New Drug and has not been approved for any indication.
Loading...
Loading...
Posted In: NewsFDA
Benzinga simplifies the market for smarter investing

Trade confidently with insights and alerts from analyst ratings, free reports and breaking news that affects the stocks you care about.

Join Now: Free!

Loading...