New Research Highlights an Investigational Single-Entity Formulation Hydrocodone Bitartrate Extended-Release Tablet at PAINWeek

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Sep 04, 2014, 04:00 ET

STAMFORD, Conn., Sept. 4, 2014 /PRNewswire/ -- Purdue Pharma is presenting results from several studies and post-hoc analyses evaluating extended-release, single-entity hydrocodone bitartrate tablets, including the analgesic effectiveness and safety among patients transitioning from immediate-release hydrocodone combination products and the formulation's abuse-deterrent potential in recreational opioid abusers at PAINWeek national conference Sept. 2 – 6 in Las Vegas.

Purdue Pharma L.P. logo. (PRNewsFoto/Purdue Pharma L.P.) (PRNewsFoto/) (PRNewsFoto/)

Purdue Pharma's investigational pain medication, once-daily hydrocodone bitartrate (which is expected to be marketed under the trade name, Hysingla™ ER) is a single-entity product that does not include acetaminophen. The tablets are formulated with 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).

Highlights of three of the several posters presented this week are as follows:

One poster, titled "Evaluation of once-daily hydrocodone (Hysingla™ ER) in users of immediate-release hydrocodone combination products," analyzed the analgesic effectiveness and safety of single-entity hydrocodone (Hysingla ER) in 20 mg to 120 mg tablets dosed once daily among patients with moderate to severe chronic pain and who were transitioning from hydrocodone products that are combined with acetaminophen. Data were from two phase 3 studies: a 12-week, placebo-controlled, double-blind study, and an open-label, long-term study with a 12-month maintenance treatment period. Among these patients in the placebo-controlled study, Hysingla ER (N=62) showed clinically meaningful and statistically significant pain relief at week 12 compared to placebo (N=67) in both primary and sensitivity analyses (deltas=0.64 to 0.98; P's = .0078 to .0357). Among patients in the long-term study, clinically significant improvements from baseline in pain relief (e.g., 30% reduction in pain) were achieved with Hysingla ER treatment, and these treatment effects were maintained throughout 12-month treatment period. Among patients who had previously used hydrocodone/acetaminophen products, adverse events were consistent with those associated with opioid analgesics. The most common treatment-emergent adverse events included constipation, nausea, vomiting, dizziness, and headache.
The next study, which is the first of two studies being presented on abuse potential, titled "Intranasal Abuse Potential Study of a Once-Daily, Single-Entity, Extended-Release Hydrocodone Tablet (Hysingla™ ER) in Recreational Opioid Users," compared the intranasal abuse potential of fine-milled and coarse-milled Hysingla ER (using an industrial mill and razor blade, respectively) to that of hydrocodone powder and placebo. Abuse potential was evaluated using pharmacokinetic measures of plasma samples and subjective pharmacodynamic measures of drug liking.
- The pharmacokinetic data showed that subjects had a higher concentration of hydrocodone in the blood following hydrocodone powder than they did following use of either fine-milled or coarse-milled Hysingla.
- The pharmacodynamic assessment showed that mean scores for overall drug liking were highest for hydrocodone powder followed by the two tampered Hysingla ER treatments and placebo. Compared with hydrocodone powder:
  - 68 percent of subjects using coarse-milled Hysingla ER had a reduction of at least 30 percent in drug liking where 64 percent had a reduction of at least 50 percent, and 44 percent had a reduction of at least 90 percent.
  - 72 percent of subjects using fine-milled Hysingla ER had a reduction of at least 30 percent in drug liking where 64 percent had a reduction of at least 50 percent, and 36 percent had a reduction of at least 90 percent.
The second of the two abuse-potential studies presented, titled "Oral Abuse Potential Study of a Once-Daily, Single-Entity, Extended-Release Hydrocodone Tablet (Hysingla™ ER) in Recreational Opioid Users," compared the oral abuse potential of Hysingla ER when chewed or when milled with an industrial mill to that of the intact Hysingla ER, immediate release hydrocodone solution and placebo. Abuse potential was evaluated using pharmacokinetic measures of plasma samples and subjective pharmacodynamic measures of drug liking.
- The pharmacokinetic results showed higher concentrations of hydrocodone among subjects using immediate release hydrocodone solution than subjects using milled, chewed or intact Hysingla ER, and the time to achieve maximum concentration was faster among subjects using hydrocodone IR than those using milled, chewed or intact Hysingla ER
- The pharmacodynamic assessments showed that mean scores for overall drug liking were highest for hydrocodone IR solution and milled Hysingla ER. Compared to the hydrocodone IR solution:
  - 83 percent of subjects using intact Hysingla ER had a reduction of at least 30 percent in drug liking where 74 percent had a reduction of at least 50 percent, and 37 percent had a reduction of at least 90 percent.
  - 69 percent of subjects using chewed Hysingla ER had a reduction of at least 30 percent in drug liking where 60 percent had a reduction of at least 50 percent, and 29 percent had a reduction of at least 90 percent.
  - 17 percent of subjects using milled Hysingla ER had a reduction of at least 30 percent in drug liking where 9 percent had a reduction of at least 50 percent, and 6 percent had a reduction of at least 90 percent.

"These studies continue to support the fact that, if approved by the Food and Drug Administration, Hysingla ER could be an important alternative for healthcare professionals treating patients in chronic pain with a hydrocodone product formulated with physicochemical properties intended to deter abuse," said Todd Baumgartner, M.D., MPH, Vice President of Research & Development and Chief Medical Officer at Purdue Pharma which funded the research.

The opioid hydrocodone in combination with acetaminophen (Vicodin® and its generic formulations) is the most commonly prescribed opioid analgesics in the United States.¹ However, acetaminophen may cause liver toxicity (i.e., hepatotoxicity), including serious liver failure, when a patient exceeds the total recommended dosage of less than 4g per day,² prompting the need for an extended release option without acetaminophen.

Immediate release hydrocodone combination products are also the most widely abused (nonmedical use) according to the Substance Abuse and Mental Health Services Administration.³ Currently available hydrocodone formulations do not incorporate abuse-deterrent technologies.

The U.S. Food and Drug Administration (FDA) recently granted Priority Review designation to Purdue's new drug application requesting approval to market Hysingla ER, which incorporates abuse-deterrent properties.

About Chronic Pain
Purdue is a leader in developing treatment options for the management of chronic pain, which is one of the most common reasons for visits to healthcare professionals. Chronic pain conditions affect more than 100 million U.S. adults and cost the American economy as much as $635 billion each year in direct healthcare expenses and lost productivity.

About Purdue Pharma L.P.
Purdue Pharma L.P. and its associated U.S. companies are privately-held pharmaceutical companies known for pioneering research on chronic pain. Headquartered in Stamford, CT, Purdue is engaged in the research, development, production, and distribution of both prescription and over-the-counter medicines and hospital products. Additional information about Purdue can be found at www.purduepharma.com.

¹ U.S. Pharmaceutical Sales - Q4 2013, Drugs.com, Accessed 09/04/2014
² Ferguson E, Nelson L. 2009. Silver Spring, MD: Food and Drug Administration. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/UCM179888.pdf. Accessed 09/04/14.
³ 2012 National Household Survey on Drug Use and Health, Table 1.89A, Substance Abuse and Mental Health Services Administration. Accessed 09/04/2014

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SOURCE Purdue Pharma L.P.