Acura Pharmaceuticals, Inc. announced that results from clinical study AP-LTX-301 (Study 301) for its LIMITx™ excess oral abuse deterrent drug LTX-03 identified a formulation that it believe optimizes the balance between providing therapeutic blood levels of drug for pain relief at a single tablet dose while retarding the bioavailability of drug when higher buffer levels are ingested. The Company intends to submit an Investigational New Drug application (IND) for LTX-03 to the US Food and Drug Administration (FDA) in the first quarter of 2018 and advance to clinical development for a New Drug Application (NDA). Current FDA approved abuse deterrent opioid formulations do not address abuse by swallowing excess numbers of tablets. The patented LIMITx technology works by neutralizing stomach acid with buffering ingredients as increasing numbers of tablets are swallowed and relies on stomach acid to play a role in the release and subsequent systemic absorption of the active ingredient from micro-particles contained in the tablets. Prior clinical studies demonstrated the ability of LIMITx tablets to deliver efficacious levels of drug with no buffering added while reducing the maximum blood level (Cmax) by up to 65% when multiple tablet are ingested. Study 301 was designed to determine the optimal buffer level per tablet. Study 301 was an open-label, parallel design pharmacokinetic study testing Acura’s LIMITx formulation LTX-03 in 72 healthy adult subjects randomized into 9 groups (8 subjects per group). One group swallowed a single Norco® 10/325mg tablet, the marketed comparator or reference drug. The remaining 8 groups swallowed a single LTX-03 tablet with increasing buffering amounts starting with no buffer, LTX-03 formulation A through H, respectively. All 72 subjects completed the study and the doses were generally well tolerated with no serious adverse events. One subject in the Formulation E group was not analyzed due to emesis. LTX-03 is a combination of hydrocodone bitartrate and acetaminophen. In study 301 bioequivalence (BE) was examined to generate information for future registration studies. Results demonstrated a trend toward BE for both active ingredients in LTX-03 formulations A through E, with one at no buffer and four at lower buffer strength tablets. Formulation E had BE ratios (log transformed) for hydrocodone of 0.89 and 0.97 for Cmax and Area Under the Curve (AUC), respectively. In this small sample size study both hydrocodone BE confidence intervals were below the acceptable lower BE range of 0.80 at 0.74 and 0.79 for Cmax and AUC, respectively. For acetaminophen, Formulation E’s BE Ratios were 1.15 and 1.03 for Cmax and AUC, respectively. While the acetaminophen AUC’s met the BE standards, the Cmax upper confidence interval of 1.61 was above the acceptable upper BE range of 1.25. The Company believes that bioequivalence of this formulation may be achieved by reducing data variability that can be achieved through an adequately powered crossover study design with sufficient numbers of subjects in the study. For LTX-03 Formulations F though H, the higher buffer level tablets, Study 301 demonstrated a progressively increasing reduction in hydrocodone Cmax culminating in a 34% Cmax reduction associated with Formulation H, the highest level evaluated. The Cmax for acetaminophen did not decline in Formulations F through H in Study 301.