The FDA has issued a complete response letter (CRL) regarding the new drug application for Apadaz (benzhydrocodone/acetaminophen, KemPharm, Inc.), an investigational abuse-deterrent product candidate for the short-term management of acute pain. The FDA issues CRLs to indicate that the agency considers the review cycle for an application to be complete and that the application is not ready for approval in its present form.
Apadaz is an immediate-release fixed-dose combination product consisting of benzhydrocodone hydrochloride, a prodrug of hydrocodone and benzoic acid, and acetaminophen. KemPharm was seeking a proposed indication for the short-term management (no more than 14 days) of acute pain. The company submitted its new drug application in December 2015.
Apadaz was developed to provide deterrence against non-oral routes of abuse. It was not designed to provide barriers against oral abuse, even though epidemiological data have shown that oral use is the most common route of abuse for hydrocodone immediate-release combination products. Currently, there are no marketed immediate-release formulations of hydrocodone with abuse-deterrent properties.
Apadaz is bioequivalent to Norco (acetaminophen/hydrocodone, Actavis). A study of the safety and gastrointestinal effects of Apadaz compared with those of Norco found that the total digestive transit times and the incidence of gastrointestinal adverse events of the two products were similar. Study results did not support a lower oral abuse potential for Apadaz compared with Norco.
Sources: KemPharm; June 13, 2016; and FDA Briefing Document; May 5, 2016.