PALATINE, IL, USA I September 29, 2014 I Acura Pharmaceuticals Inc. (NASDAQ: ACUR) announced today preliminary results from three clinical studies for its abuse deterrent AVERSION® hydrocodone bitartrate with acetaminophen (AVERSION H/A) development product with the key study demonstrating that AVERSION H/A met the objective of conformance with the Food and Drug Administration’s (FDA) standards for bioequivalence when compared to the reference drug NORCO®, when taken in the fasted state. A food effect was observed with the AVERSION H/A formulation with lower peak blood concentrations for both hydrocodone and acetaminophen than the comparator product.
Further, the studies demonstrated dose proportionality, or relatively consistent blood exposure, across all three dosage strengths of AVERSION H/A. Finally, Acura evaluated blood levels of hydrocodone compared to VICOPROFEN® and of acetaminophen compared to ULTRACET®, for additional safety. AVERSION H/A blood levels of hydrocodone were consistent with the comparator product while acetaminophen peak blood levels were higher than those observed for the comparator product.
AVERSION H/A was generally well tolerated in all the clinical studies with no serious adverse events observed. AVERSION H/A exhibited consistent exposure levels of hydrocodone and acetaminophen across all three studies. Acura continues to review the results from these studies.
The three Acura studies, Study AP-ADF-302, AP-ADF-303 and AP-ADF-304, conclude Acura’s planned clinical studies to demonstrate the pain relief efficacy and safety of AVERSION H/A. Acura believes the level of food effect observed and the increased peak exposure to acetaminophen are not clinically relevant, but all these results will be subject to FDA review and concurrence. Acura has previously indicated the need to provide additional clinical data on the snorting abuse deterrent features of AVERSION H/A which is pending the successful completion of a dispute resolution proceeding Acura initiated with the FDA regarding FDA’s determination that snorting is not a relevant route of abuse for hydrocodone combination products.
Study AP-ADF-302 is an open label, single dose, randomized, crossover study in 36 healthy adult subjects measuring blood concentration of hydrocodone and acetaminophen in fed and fasted states. In the fasted state, a single AVERSION H/A 10/325mg tablet was found to meet FDA’s standards for bioequivalence compared to an equivalent dose of NORCO. A finding of bioequivalence compared to an FDA approved drug is typically sufficient to establish the safety and efficacy of a test formulation. AVERSION H/A 10/325mg was also tested in the fed state following a standardized meal, which demonstrated a 13.7% and 34.4% average reduction in peak blood concentration for hydrocodone and acetaminophen, respectively, compared to NORCO in the fasted state. These food effect results are consistent with the AVERSION technology and also the known effect of food on acetaminophen in general and the reduction is not expected to have a meaningful clinical impact.
Study AP-ADF-303 is an open label, single dose, randomized, crossover study in 24 healthy adult subjects measuring blood concentration of hydrocodone and acetaminophen in the fasted state across three different dose levels of AVERSION H/A. The blood exposure of hydrocodone and acetaminophen were proportionately the same across all three doses of AVERSION H/A successfully demonstrating dose consistency of the formulation.
Study AP-ADF-304 is an open label, single dose, randomized, crossover study in 24 healthy adult subjects measuring blood concentration of hydrocodone and acetaminophen in the fasted state to determine pharmacokinetics and safety of AVERSION H/A 7.5/325mg compared to equivalent doses of VICOPROFEN (for hydrocodone) and ULTRACET (for acetaminophen), for additional safety. Extent of exposure, measured by Area Under the Curve or AUC, is comparable for both hydrocodone and acetaminophen between AVERSION H/A and the respective comparator products. The peak exposure, measured by maximum plasma concentration or Cmax, is consistent for hydrocodone but AVERSION H/A was approximately 23% higher than the comparator based on the geometric mean. A large variability in acetaminophen results is observed in the study and is being further evaluated.
About Acura Pharmaceuticals
Acura Pharmaceuticals is a specialty pharmaceutical company engaged in the research, development and commercialization of product candidates intended to address medication abuse and misuse, utilizing its proprietary LIMITX™, AVERSION® and IMPEDE® Technologies. LIMITX™ contains ingredients that are intended to reduce or limit the rate or extent of opioid release when multiple tablets are ingested. AVERSION® contains polymers that cause the drug to gel when dissolved; it also contains compounds that irritate the nasal passages. IMPEDE® is designed to disrupt the processing of pseudoephedrine from tablets into methamphetamine.
In June 2011, the U.S. Food and Drug Administration approved our oxycodone HCl immediate-release tablets which incorporate the AVERSION® Technology. The Company has a development pipeline of additional AVERSION® Technology products containing other opioids.
In December 2012, the Company commenced commercialization of NEXAFED® [pseudoephedrine hydrochloride (HCl)], a 30 mg immediate-release abuse-deterrent decongestant. The next generation pseudoephedrine tablet combines effective nasal congestion relief with IMPEDE® Technology, a unique polymer matrix that disrupts the conversion of pseudoephedrine into the dangerous drug, methamphetamine.
SOURCE: Acura Pharmaceuticals
Post Views: 218
PALATINE, IL, USA I September 29, 2014 I Acura Pharmaceuticals Inc. (NASDAQ: ACUR) announced today preliminary results from three clinical studies for its abuse deterrent AVERSION® hydrocodone bitartrate with acetaminophen (AVERSION H/A) development product with the key study demonstrating that AVERSION H/A met the objective of conformance with the Food and Drug Administration’s (FDA) standards for bioequivalence when compared to the reference drug NORCO®, when taken in the fasted state. A food effect was observed with the AVERSION H/A formulation with lower peak blood concentrations for both hydrocodone and acetaminophen than the comparator product.
Further, the studies demonstrated dose proportionality, or relatively consistent blood exposure, across all three dosage strengths of AVERSION H/A. Finally, Acura evaluated blood levels of hydrocodone compared to VICOPROFEN® and of acetaminophen compared to ULTRACET®, for additional safety. AVERSION H/A blood levels of hydrocodone were consistent with the comparator product while acetaminophen peak blood levels were higher than those observed for the comparator product.
AVERSION H/A was generally well tolerated in all the clinical studies with no serious adverse events observed. AVERSION H/A exhibited consistent exposure levels of hydrocodone and acetaminophen across all three studies. Acura continues to review the results from these studies.
The three Acura studies, Study AP-ADF-302, AP-ADF-303 and AP-ADF-304, conclude Acura’s planned clinical studies to demonstrate the pain relief efficacy and safety of AVERSION H/A. Acura believes the level of food effect observed and the increased peak exposure to acetaminophen are not clinically relevant, but all these results will be subject to FDA review and concurrence. Acura has previously indicated the need to provide additional clinical data on the snorting abuse deterrent features of AVERSION H/A which is pending the successful completion of a dispute resolution proceeding Acura initiated with the FDA regarding FDA’s determination that snorting is not a relevant route of abuse for hydrocodone combination products.
Study AP-ADF-302 is an open label, single dose, randomized, crossover study in 36 healthy adult subjects measuring blood concentration of hydrocodone and acetaminophen in fed and fasted states. In the fasted state, a single AVERSION H/A 10/325mg tablet was found to meet FDA’s standards for bioequivalence compared to an equivalent dose of NORCO. A finding of bioequivalence compared to an FDA approved drug is typically sufficient to establish the safety and efficacy of a test formulation. AVERSION H/A 10/325mg was also tested in the fed state following a standardized meal, which demonstrated a 13.7% and 34.4% average reduction in peak blood concentration for hydrocodone and acetaminophen, respectively, compared to NORCO in the fasted state. These food effect results are consistent with the AVERSION technology and also the known effect of food on acetaminophen in general and the reduction is not expected to have a meaningful clinical impact.
Study AP-ADF-303 is an open label, single dose, randomized, crossover study in 24 healthy adult subjects measuring blood concentration of hydrocodone and acetaminophen in the fasted state across three different dose levels of AVERSION H/A. The blood exposure of hydrocodone and acetaminophen were proportionately the same across all three doses of AVERSION H/A successfully demonstrating dose consistency of the formulation.
Study AP-ADF-304 is an open label, single dose, randomized, crossover study in 24 healthy adult subjects measuring blood concentration of hydrocodone and acetaminophen in the fasted state to determine pharmacokinetics and safety of AVERSION H/A 7.5/325mg compared to equivalent doses of VICOPROFEN (for hydrocodone) and ULTRACET (for acetaminophen), for additional safety. Extent of exposure, measured by Area Under the Curve or AUC, is comparable for both hydrocodone and acetaminophen between AVERSION H/A and the respective comparator products. The peak exposure, measured by maximum plasma concentration or Cmax, is consistent for hydrocodone but AVERSION H/A was approximately 23% higher than the comparator based on the geometric mean. A large variability in acetaminophen results is observed in the study and is being further evaluated.
About Acura Pharmaceuticals
Acura Pharmaceuticals is a specialty pharmaceutical company engaged in the research, development and commercialization of product candidates intended to address medication abuse and misuse, utilizing its proprietary LIMITX™, AVERSION® and IMPEDE® Technologies. LIMITX™ contains ingredients that are intended to reduce or limit the rate or extent of opioid release when multiple tablets are ingested. AVERSION® contains polymers that cause the drug to gel when dissolved; it also contains compounds that irritate the nasal passages. IMPEDE® is designed to disrupt the processing of pseudoephedrine from tablets into methamphetamine.
In June 2011, the U.S. Food and Drug Administration approved our oxycodone HCl immediate-release tablets which incorporate the AVERSION® Technology. The Company has a development pipeline of additional AVERSION® Technology products containing other opioids.
In December 2012, the Company commenced commercialization of NEXAFED® [pseudoephedrine hydrochloride (HCl)], a 30 mg immediate-release abuse-deterrent decongestant. The next generation pseudoephedrine tablet combines effective nasal congestion relief with IMPEDE® Technology, a unique polymer matrix that disrupts the conversion of pseudoephedrine into the dangerous drug, methamphetamine.
SOURCE: Acura Pharmaceuticals
Post Views: 218
