Extended-Release Hydrocodone with Abuse-Deterrent Properties

Phoenix—Healthy people who are not physically dependent on opioids are less likely to abuse hydrocodone extended-release (ER) if the tablets contain abuse-deterrent properties, according to a randomized, double-blind, triple-dummy, placebo-controlled, crossover study.

The study’s results were presented at the AAPM meeting during a poster session titled Evaluation of the Abuse Potential of an Extended-Release Hydrocodone Bitartrate Tablet Formulated with Abuse-Deterrence Technology in Non-Dependent, Recreational Opioid Users.

The authors mentioned that hydrocodone in combination with acetaminophen is the most commonly prescribed treatment in the United States. They added that most hydrocodone products to treat pain are immediate-release and used in combination with analgesics, such as acetaminophen, ibuprofen, and aspirin. Although ER formulations require a total drug load, they may have less potential for abuse, according to the authors.

In this study, the authors examined an investigational, 45 mg single-agent ER formulation of hydrocodone bitartrate taken orally twice daily that includes abuse-deterrent technology. The drugs are resistant when patients attempt to crush the pills or take them with alcohol.

The trial included healthy patients 18 to 50 years of age with a body mass index (BMI) between 18 kg/m² and 32 kg/m² and those with a history of opioid use in order to get high at least 10 times in the past year and at least once in the 12 weeks prior to screening. They were also not physically dependent on opioids, had a negative urine drug screening, and had a negative alcohol breath test.

Patients were excluded if they had any clinically significant uncontrolled medical condition; abnormalities in laboratory, electrocardiogram, or physical examination findings; or a history of drug or alcohol abuse and heavy smoking.

Of the 45 patients evaluated for pharmacodynamic analysis, 94% were white and 80% were male. The patients ranged in age from 18 to 43 years and had a BMI range of 19.5 kg/m² to 32.6 kg/m².

The authors evaluated drug liking by using the Drug Liking and Effects Questionnaire. They found there was a significantly lower drug liking after administering intact and crushed hydrocodone ER compared with hydrocodone immediate-release. After patients received immediate-release hydrocodone, drug liking peaked almost immediately and then declined to the baseline level approximately 12 weeks later. Patients who received crushed ER hydrocodone had a slower increase to a lower peak drug liking, while patients who received intact ER hydrocodone had minimal drug liking that was comparable to a placebo group.

When using the Visual Analog Scale drug liking measurement, the authors found that there was significantly lower drug liking in patients who received intact and crushed ER hydrocodone compared with those who took immediate-release hydrocodone. Drug liking following 24 hours was similar between patients who received intact ER hydrocodone and those who received crushed ER hydrocodone.

During the study, there were no deaths or serious adverse events, although there was a death due to a self-inflicted gun shot wound reported approximately 2.5 hours after the study ended. Two patients discontinued the study due to adverse events after they received intact ER hydrocodone: 1 for a toothache and 1 for catheter site cellulitis. The authors mentioned that neither of those instances was related to the study’s medication.

Adverse events were reported in 79% of patients in the immediate-release group, 53% of patients in the intact ER group, and 73% of patients in the crushed ER group. Most of the adverse events were mild, according to the authors.—Tim Casey

This study was sponsored by Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd.