Acura Pharmaceuticals, Inc. announced that preliminary topline results from study AP-LTX-311 successfully demonstrated that a nine-tablet dose of LTX-03 (hydrocodone bitartrate and acetaminophen tablets) had mean peak plasma concentrations (Cmax) of hydrocodone 16% lower than a two-tablet dose of LTX-03 and 30% lower than expected from a marketed reference standard. The 2-tablet LTX-03 dose mean Cmax was 83% compared to the reference standard. LTX-03 tablets incorporate Acura?s LIMITx?

technology in the hydrocodone component of the tablet which is designed to mitigate the risks of drug overdose by retarding the release of the hydrocodone as excessive tablets are ingested. The acetaminophen component is not subject to the LIMITx technology and demonstrated mean Cmax of 100% of the reference standard. Mean total exposure of drug (measured by Area Under the Curve or AUC) for both hydrocodone and acetaminophen in LTX-03 were comparable to the reference standard with amounts ranging from 90% to 113%.

Study 311 was a randomized, crossover bioavailability study in fasted healthy adult subjects taking 2, 5 and 9 tablet doses of LTX-03 10/325mg tablets to simulate drug overdose. All subjects received doses of naloxone, an opioid blocker. 30 subjects completed at least 1 study dose, 28 subjects completed all doses, and 4 doses were excluded from analysis due to aberrant pre-dose data.

There were no reported serious adverse events. Reported adverse events were mild and consistent with those typically reported with hydrocodone and acetaminophen tablets. LTX-03 tablets were well-tolerated.

Means reported are based on geometric mean calculations and denominated as ng/mL for Cmax and hr*ng/mL for AUC. Mean hydrocodone results for the 2, 5 and 9 tablet doses on a per tablet basis were 20.6, 21.8, and 17.2 for Cmax and 143.5, 159.4, and 162.2 for AUC. Mean acetaminophen results for the 2, 5 and 9 tablet doses on a per tablet basis were 4895, 5560, and 4767 for Cmax and 13650, 15580, and 17222 for AUC.

As a comparison, the geometric mean CMax for a single, fasted NORCO (hydrocodone bitartrate and acetaminophen) 10/325mg tablet dose observed in a separate study from 2012 owned by Acura was 24.7 and 4753 for hydrocodone and acetaminophen, respectively. The AUC for NORCO was 149.9 and 15220 for hydrocodone and acetaminophen, respectively. NORCO tablets have been discontinued from the US market but previously served as the FDA?s reference standard.

LTX-03 is an investigational drug for the treatment of pain. The LIMITx technology incorporates the hydrocodone bitartrate ingredient in an acid soluble micro-particle and acid neutralizing ingredients in the broader tablet which is designed to slow the dissolution, release and subsequent systemic absorption of the hydrocodone when excessive tablets are ingested. Hydrocodone is an opioid analgesic whose overdose can induce respiratory depression possibly leading to death.

Study 311 included an exploratory arm in which study completers were randomized to take a 2, 5 or 9 tablet LTX-03 dose with 7.5 ounces of an acidic beverage (as opposed to water). On a dose normalized basis, the acidic beverage increased the hydrocodone Cmax by 18%, decreased the acetaminophen Cmax by 19%, and had less than a 10% effect on AUC of both hydrocodone and acetaminophen. The final Study 311 report and analysis is expected to be completed as soon as possible, at which time Acura and its LTX-03 partner, Abuse Deterrent Pharma, LLC, plan to move forward with a New Drug Application submission to the FDA with an expected request for priority review.