LIMITX Technology

LIMITX Technology is intended to address an oral Excessive Tablet Abuse (ETA) or accidental consumption of multiple tablets and provide a margin of safety during accidental over-ingestion of tablets. LIMITX is also expected to exhibit barriers to abuse by snorting and injection.

Status

LTX-03, an immediate-release hydrocodone bitartrate with acetaminophen tablet, is our lead LIMITX development program.

Previously, we have run two exploratory human pharmacokinetic studies, AP-LTX-400 & AP-LTX-401, on LTX-04P. These studies demonstrated:

  • we have too much buffer ingredient in a single tablet so that the micro-particles are not completely and immediately releasing all of the drug even at a single tablet
  • up to a 65% reduction in maximum plasma concentration (Cmax) when multiple tablets are ingested.

Based on the above conclusions for Studies 400 & 401, we then completed Study AP-LTX-300 (Study 300), the first study for LTX-03 which was a buffer dose ranging study. This study included an active component that contained 10mg of hydrocodone bitartrate micro-particles and 325mg of acetaminophen. The active component did not contain any buffering capacity. We also produced a buffering component which had a fraction of the buffering capacity that was used in previous Studies 401 & 401 for product LTX-04. For this study, we encapsulated the active component with an incremental number of buffering units. Subjects in the first group of this study were placed into one of seven subgroups and were administered with either no buffering units or up to 5 buffering units. The second group was only be administered an encapsulated commercially available reference product containing 10mg of hydrocodone bitartrate and 325mg of acetaminophen as a positive control. Our goal in this study was to identify the highest buffer level that allowed for a full release of hydrocodone at a single tablet dose relative to the positive control before the LIMITX buffering effect is observed.

Since the results of Study 300 were unable to identify a precise buffer level for a single LIMITX tablet due to the erratic release of the drug from the over-encapsulated tablets that was used in the Study. We conducted another dose ranging study, AP-LTX-301 (Study 301), without using over-encapsulated tablets in December 2017. We believe that Study 301 identified a formulation that 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.

We intend to advance LTX-03 to clinical development for a New Drug Application, to which an IND (Investigational New Drug Application) was submitted to the FDA in the first quarter of 2018, effective April 2018. We have begun the scale-up of the commercial manufacturing process during the second quarter of 2018, however we may run additional exploratory studies before manufacturing scale-up is complete to further understand the LIMITX Technology.