Purdue Pharma seeks FDA authorization to market once-daily hydrocodone bitartrate tablet

Purdue Pharma L.P. announced that it has filed a New Drug Application (NDA) with the U.S. Food & Drug Administration (FDA) seeking authorization to market a once-daily, single-entity hydrocodone bitartrate tablet (HYD).  This investigational pain medication was formulated to incorporate abuse-deterrent properties designed to make the product more difficult to manipulate for the purpose of misuse or abuse by various routes of administration (e.g., chewing, snorting and intravenous injection). The formulation has not exhibited alcohol-induced dose dumping in laboratory studies. Data from clinical trials assessing the safety, efficacy, and abuse liability of this investigational medication are also being presented today at the 33^rd Annual Scientific Meeting of the American Pain Society (APS) in Tampa, Fla.

"This is another important step in our efforts to develop a portfolio of pain medications with abuse-deterrent technology," said Mark Timney, President and CEO of Purdue Pharma. "I'm proud of Purdue's leadership role in this important area of pharmaceutical innovation."

"Healthcare professionals need an array of therapeutic options in order to individualize the care they provide to their patients with chronic pain," said Todd Baumgartner, MD, MPH, Vice President of Regulatory Affairs and Chief Medical Officer at Purdue Pharma.  "If approved by the FDA, we believe this product will be a valuable therapy for use in treating chronic pain that is also expected to deter misuse and abuse by various routes of administration." 

Study data assessing HYD's safety and efficacy as well as data from studies of HYD's abuse potential, conducted in accordance with FDA draft guidance on development of abuse-deterrent formulations, are being presented at the APS meeting, including:

• "Long-term Safety and Effectiveness of Once-daily, Single-entity, Abuse-deterrent Hydrocodone in Chronic Nonmalignant and Nonneuropathic Pain: Results of a Long-term Open-label Study"
   W. Wen, L. Taber, S. Yu Lynch, E. He, C. Munera, S. Ripa

This study, with a 52-week maintenance-treatment period involving 922 patients, evaluated the safety and persistence of analgesic effect of HYD in both opioid-naive and opioid-experienced subjects with moderate to severe chronic nonmalignant and nonneuropathic pain. HYD was generally well tolerated, with the most common treatment-emergent adverse events being those typically associated with the use mu opioid analgesics, and no unanticipated safety concerns were identified. Comprehensive audiologic testing did not reveal any ototoxicity associated with HYD. During maintenance HYD treatment, persistence of analgesia and improvement in function were achieved with stable HYD doses. Short‐acting opioid use was stable at a reduced level from screening baseline during the 52‐week HYD treatment period.

• "A Single-Center, Randomized, Double-blind Crossover Study to Evaluate the Abuse Potential, Pharmacokinetics and Safety of Intranasally Administered Extended-Release Hydrocodone in Recreational Opioid Users"
  S. Harris, S. Colucci, R. Kapil, A. Cipriano, S. O'Keefe, P. Perrino, P. Geoffroy, T. Hopyan, N. Levy-Cooperman

The intranasal abuse-deterrent properties of HYD were evaluated in 31 healthy, non-dependent subjects with a history of recreational opioid drug use. Subjects received four intranasal treatments (coarse HYD particles, fine HYD particles, hydrocodone powder, and placebo) in a randomized, double-blind, crossover fashion. The fine HYD particle treatment, produced using an industrial mill, was included to test the limits of the abuse-deterrent technology. A primary endpoint for the study was drug liking, measured up to 36 hours after dosing using a visual analogue scale (VAS). The results showed that tampered HYD (coarse and fine particles) had significantly lower intranasal abuse potential than hydrocodone powder.

As compared to hydrocodone powder, 68 percent of subjects had a reduction of at least 30 percent in maximum drug liking score following coarse HYD, and 64 percent of subjects had a reduction of at least 50 percent. When fine HYD was compared to hydrocodone powder, 72 percent of subjects had a reduction of at least 30 percent in maximum drug liking score, and 64 percent of subjects had a reduction of at least 50 percent.

• "A Single-Center, Randomized, Double-Blind, Crossover Study to Evaluate the Abuse Potential, Pharmacokinetics, and Safety of Oral Intact, Chewed, and Milled Extended-Release Hydrocodone (HYD) Tablets in Recreational Opioid Users"
  S. Harris, S. Colucci, R. Kapil, A. Cipriano, S. O'Keefe, P. Perrino, P. Geoffroy, T. Hopyan, N. Levy-Cooperman

The oral abuse-deterrent properties of HYD were evaluated in 35 healthy, non-dependent recreational opioid drug users. Subjects received HYD intact, HYD chewed, HYD milled, hydrocodone solution, and placebo in a randomized, double-blind, crossover fashion. The HYD milled treatment, produced using an industrial mill, was included to test the limits of the abuse-deterrent technology. A primary endpoint for the study was drug liking, measured up to 36 hours after dosing using a visual analogue scale (VAS).  The results showed that HYD intact and HYD chewed had significantly lower drug liking scores than hydrocodone solution.

As compared to hydrocodone solution, 83 percent of subjects had a reduction of at least 30 percent in maximum drug liking score following intact HYD, and 74 percent of subjects had a reduction of at least 50 percent. When chewed HYD was compared to hydrocodone solution, 69 percent of subjects had a reduction of at least 30 percent in maximum drug liking score, and 60 percent of subjects had a reduction of at least 50 percent. When milled HYD was compared to hydrocodone solution, 17 percent of subjects had a reduction of at least 30 percent in maximum drug liking score, and 9 percent of subjects had a reduction of at least 50 percent.

• "In Vitro Assessment of the Effects of Alcohol on the Release Rate of Hydrocodone Bitartrate from a Once-daily, Single-Entity, Hydrocodone Bitartrate Formulation" 
  Jennifer Giordano, Hugh Huang, Jenny Kianto

This in vitro dissolution study evaluated the effects of varying ethanol (EtOH) concentrations in simulated gastric fluid (SGF) (4 % EtOH/96% SGF, 10% EtOH/90% SGF, 20% EtOH/80% SGF, 40% EtOH/60% SGF) on the rate of release of hydrocodone from HYD tablets.  The results showed that, as the percentage of alcohol in SGF was increased, the rate of release of hydrocodone from the HYD formulation decreased.

Purdue has also conducted a series of additional laboratory-based in vitro abuse-deterrence studies with this investigational formulation. These data along with the results of the human clinical studies have been submitted to the FDA as part of the New Drug Application.

Hydrocodone products are the most commonly prescribed opioid analgesics in the United States. They are also the most widely abused (nonmedical use), according to the Substance Abuse and Mental Health Services Administration. Currently available hydrocodone formulations do not incorporate abuse-deterrent technologies. 

SOURCE Purdue Pharma L.P.