Acura Pharmaceuticals, Inc., a specialty pharmaceutical company, has reported top-line results from Study AP-ADF-301 (Study 301), a phase II clinical study in 40 recreational drug abusers assessing the abuse liability of snorting a crushed hydrocodone bitartrate with acetaminophen tablet formulated with its abuse deterrent AVERSION technology (AVERSION H&A).
The results for AVERSION H&A in Study 301 were consistent in certain respects with the results of a similar study for another AVERSION product containing oxycodone hydrochloride, which has been approved by the US Food and Drug Administration (FDA). Study 301's primary endpoint indicated AVERSION H&A had slightly lower numeric mean maximum drug liking (Emax: 72.1) compared to an equivalent dose of a generic hydrocodone/ acetaminophen tablet (Generic H&A: Emax: 75.6) currently on the market, however these results were not statistically significant (p > 0.025).
The secondary endpoints demonstrated the effects of the AVERSION ingredients on drug snorting. AVERSION H&A's mean minimum liking (Emin: 40.2) was less than Generic H&A (Emin: 50.4) (the difference being statistically significant at p=0.0003). The mean minimum drug liking for AVERSION H&A and the placebo control were 40.2 and 48.8, respectively (the difference being statistically significant at p=0.0042). A score below 50 indicates a subject disliked the drug they were taking at some point during the treatment (a score of 50 means neither like or dislike), and a score greater than 50 indicates they liked the drug they were taking.
The mean minimum liking results correlated closely the Overall Drug Liking score (ODL) and Take Drug Again assessment (TDA). ODL assessed the subject like or dislike for the drug experience 12 hours after taking the dose. The ODL for AVERSION H&A (52.7) was lower than Generic H&A (71.0) (the difference being statistically significant at p=0.0001) with a score of 50 indicating a neither a like or dislike. TDA assessed a subject's willingness to take the drug again assessed 12 hours after taking the dose. The TDA for AVERSION H&A (45.1) was lower than Generic H&A (71.0) (the difference being statistically significant at p=0.0001) with the AVERSION H&A score below 50 indicating an unwillingness to take the drug again.
There were no serious adverse events reported for AVERSION H&A. There was no sequence effect identified in the study but a carryover effect between the five study crossover periods was identified for the Emax measure but not the Emin measure. This effect is being further evaluated.
Acura intends to further evaluate the data from this study and plans to meet with the FDA to discuss these results. AVERSION H&A tablets contain a unique composition of inactive ingredients intended to deter common methods of prescription drug abuse such as snorting. Given the absence of statistical significance in Study 301s primary endpoint relating to maximum drug liking, the timeline for submission of a New Drug Application (NDA) for AVERSION H&A is expected to be delayed. The revised projected timeline for submission of the NDA for Aversion H&A will be determined following our meeting with the FDA. Although we do not expect the need to conduct additional nasal abuse like/dislike studies for AVERSION H&A, this will not be confirmed until our meeting with the FDA to discuss the Study 301 results.
Some of the significant differences observed in Study 301 compared to the results seen for the AVERSION oxycodone hydrochloride product study include, but are not limited to: (a) mean maximum drug liking scores for the active comparator (i.e. Generic H&A) were significantly lower, (b) the time to mean minimum drug liking for AVERSION H&A was longer, (c) almost all AVERSION H&A subjects snorted the entire dose compared to only 48% for AVERSION oxycodone hydrochloride, and (d) AVERSION oxycodone hydrochloride achieved a statistically significant reduction in mean maximum drug liking scores before adjusting for an observed sequence effect.
Study 301 was a phase II, single-centre, randomized, double-blind, five-period crossover assessment of the abuse liability potential of snorting crushed AVERSION H&A tablets. Fourty subjects with a history of insufflating opioids were randomized into the treatment phase of the study after demonstrating they could adequately distinguish euphoria or "high" (measured as drug liking) between placebo and two different doses of hydrocodone/APAP (the drug discrimination phase).
In the blinded treatment phase. fasted subjects snorted a single dose of five different crushed study drugs every 48 hours, using either 10mg or 20mg of hydrocodone bitartrate based on the lowest dose the subject could adequately distinguish in the drug discrimination phase. Study drugs were administered in a randomized crossover design. The primary study drugs were placebo, Generic H&A, and AVERSION H&A. Two active control drugs were used to blind the subjects to the different powder volumes of the primary study drugs and provide information on the impact of powder volume and the AVERSION ingredients on drug liking scores.
Subjects snorted the crushed study drugs using both nostrils over five minutes in a design to visually blind the study drugs. The primary endpoint was the subjects' maximum score (Emax) of their drug like/dislike on a 101-point visual analog scale (VAS) at various intervals following administration, with a score of 0 indicating a strong dislike, 100 a strong like and 50 a neutral response. Secondary endpoints measured on a 101-point VAS scale included the minimum score (Emin) of their drug like/dislike, the subjects' willingness to take drug again, assessment of overall drug like/dislike, and assessment of drug high. Subjects also responded to a 6-point Likert scale for nasopharyngeal and facial side effects associated with the AVERSION technology. Pharmacokinetic blood samples were also collected and analyzed for each subject.
Acura Pharmaceuticals is engaged in the research, development and commercialization of product candidates intended to address medication abuse and misuse, utilizing its proprietary AVERSION and IMPEDE technologies.