Acurox® Tablets
Acurox® (oxycodone HCl/niacin) Tablets
Acurox® is an immediate release opioid analgesic tablet with a proposed indication for relief of moderate-to-severe pain and is designed to deter common methods of misuse and abuse. Acurox® Tablets are being developed in two tablets strengths of 5/30mg and 7.5/30mg.
Status
On September 2, 2009, Acura and King met with the U.S. Food and Drug Administration (FDA) to discuss the issues raised in the FDA’s June 30, 2009 Complete Response Letter (”CRL”) following their review of the New Drug Application for Acurox® (NDA). The CRL raised issues regarding the potential abuse deterrent benefits of Acurox®. The FDA and the Companies agreed to take the NDA to an FDA Advisory Committee to consider the evidence to support the potential opioid abuse deterrent effects of Acurox® Tablets. While the FDA indicated that no new clinical trials are required at this time, Acura and King are performing an additional clinical study (Study AP-ADF-114) to further assess the abuse deterrent features of Acurox®. The FDA has not yet set a meeting date for the Advisory Committee’s review of the NDA.
If the Acurox® Tablets NDA is ultimately approved by the FDA, for which no assurances can be provided, the Companies believe Acurox® Tablets will be the first approved immediate release opioid analgesic designed to deter the most common methods of opioid misuse and abuse.
Development Program
The NDA for Acurox® Tablets includes results from numerous clinical and laboratory studies assessing the efficacy and safety of Acurox® Tablets and to demonstrate abuse deterrent features and benefits, including the data and results from studies set forth in the table below.
| Studies in the Acurox® Tablets 505(b)(2) NDA Submission (click study number for summary of results) |
|
|---|---|
| AP-ADF-101 Phase I |
Niacin dose-response (0-75mg) |
| AP-ADF-104 Phase I |
Bioequivalence to non Aversion® Technology Reference Listed Drug |
| AP-ADF-108 Phase I |
Single dose linearity and food effect |
| AP-ADF-109 Phase I |
Multi-dose linearity |
| AP-ADF-106 Phase I |
Evaluate effects of nasal snorting in subjects with a history of snorting and nasal drug abuse |
| AP-ADF-103 Phase II |
Repeat dose safety and tolerability |
| AP-ADF-107 Phase II |
Niacin dose-response (0-600mg) |
| AP-ADF-102 Phase II |
Evaluate relative dislike of oxycodone HCl/niacin versus oxycodone HCl alone |
| AP-ADF-111 Phase II |
Evaluate abuse liability of oxycodone HCl/niacin versus oxycodone HCl alone |
| AP-ADF-114 Phase II |
Assess relative abuse potential of Acurox® Tablets in non-dependent recreational opioid users |
| AP-ADF-105 Phase III |
Evaluate safety and efficacy in relief of moderate to severe pain |
| Extraction Testing | Laboratory test quantifying I.V. abuse deterrent properties |
| Syringeability Testing | Laboratory test quantifying I.V. abuse deterrent properties |
At this stage, the Company cannot provide any assurance that FDA will not require additional clinical studies for Acurox® Tablets.
Expectations Product Labeling
The FDA has publicly stated that explicit claims of abuse deterrence will not be permitted in product labeling unless such claims are supported by double blind controlled clinical studies demonstrating an actual reduction in product abuse by patients or drug abusers. We believe the cost, time and practicality of designing and implementing clinical studies adequate to support explicit labeling claims of abuse deterrence are prohibitive. The FDA has stated that scientifically derived data and information describing the physical characteristics of a product candidate and/or the results of laboratory and clinical studies simulating product abuse may be acceptable to include in the product label. We included in the proposed labeling of our NDA for Acurox® Tablets both a physical description of the abuse deterrent characteristics and information from our laboratory and clinical studies designed to simulate the relative difficulty of abusing our product candidates. The extent to which such information will be included in the FDA approved product label will be subject to discussions with and agreement by the FDA as part of the NDA review process. Because the FDA closely regulates promotional materials, even if the FDA initially approves labeling that includes a description of the abuse deterrent characteristics of the product, the FDA will continue to review the acceptability of promotional labeling claims and product advertising campaigns for our product candidates.
