Special Topics in Pain: Opioids
Abuse Potential with Oral Route of Administration of a Hydrocodone Extended-Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent, Recreational Opioids Users.
Author(s): Darwish M, et al.
Journal: Pain Med. 2016; Jun 21. 29 references.
Reprint: Mary Bond, MS, MBA, Teva Pharmaceuticals, 41 Moores Road, P.O. Box 4011, Frazer, PA 19355, USA. Email: email@example.com
Faculty Disclosure: Please see original article for disclosures. Abstracted by N Walea, who has nothing to disclose.
Objective: Review and evaluate the latest advances and newest information in the area of Opioids
Editor’s Note: This is a very thorough, well planned study of an abuse deterrent extended release hydrocodone formulation to demonstrate the effectiveness of the abuse deterrent as shown by the non preference of individuals known to have gotten “high” on recreational drugs within the past year. The non preference for this formulation speaks for its abuse potential.
A single-agent extended-release (ER) formulation of hydrocodone bitartrate (Teva Pharmaceuticals) has been developed to provide sustained pain relief with twice-daily dosing. This formulation employs CIMA® Abuse-Deterrence Technology(ADT), a novel platform that allows for controlled release of hydrocodone over an extended period and provides resistance against rapid release of hydrocodone when tablets are comminuted (broken into small pieces by crushing, milling, grating, or grinding) and resistance against dose dumping when tablets are taken with alcohol.
Hydrocodone immediate release (IR) reaches peak plasma concentrations within one to two hours and has a half-life of 4.0 to 4.5 hours, requiring repeated dosing every four to six hours for adequate management of pain.
This study enrolled 49 men and women (80% male and white 94%) with a median (range) age of 23 (18-43) years who were not physically dependent on opioids as show by successful completion of a naloxone challenge (i.e., no signs or symptoms of opioid withdrawal after administration of 0.8 mg intravenous naloxone). Subjects were required to have a history of recreational opioid use aimed at achieving a "high" at least 10 times in the last year and at least one occasion within 12 weeks before screening.
Qualified subjects entered the study phase and were randomly assigned to receive each of the following via oral route of administration once: one finely crushed 45-mg hydrocodone ER tablet; 45mg of hydrocodone bitartrate powder (representative hydrocodone IR); one intact 45-mg hydrocodone ER tablet; and placebo. Each treatment was separated by a minimum 14-day washout period.
The assessment measures included the "at the moment" drug liking question on the Drug Liking and Effects Questionnaire (DLEQ, using the parameter of peak score (maximum effect [Emax]) and pharmacodynamic measures of abuse potential in the Overall Drug Liking VAS score, (both, 100 point bipolar drug-liking visual analog scales [VAS; 0 =strong disliking, 50 =neutral, 100 =strong]). Other instruments included Take Drug Again Assessment (TDAA), and blood samples that were collected before the study and during the study at protocol specified intervals.
Significantly lower mean Emax for "at the moment" drug liking was observed after administration of intact and finely crushed hydrocodone ER compared with hydrocodone IR (53.9 and 66.9 vs 85.2, respectively). "At the moment" drug liking Emax was also significantly different after administration of intact hydrocodone ER compared with finely crushed hydrocodone ER (53.9 vs. 66.9).
The Overall Drug Liking VAS was administered at 24 hours post dose. Findings for Overall Drug Liking were comparable to those for "at the moment" drug liking. The hydrocodone IR Overall Drug Liking score was significantly higher than the scores for placebo and both intact and finely crushed hydrocodone ER. The TDAA assessment indicated subjects were significantly less likely to want to take intact or finely crushed hydrocodone ER again compared with hydrocodone IR (TDAA 46.4 and 58.7 vs 75.2, respectively).
During the treatment phase, the overall incidence of AEs were lower after administration of intact hydrocodone ER (53%) compared with crushed hydrocodone ER (73%) and hydrocodone IR (79%). No clinically relevant mean changes from baseline were noted for serum chemistry and hematology.
The outcomes for secondary measures showed that positive, negative and sedative drug effects were diminished with intact and finely crushed hydrocodone ER tablet compared with hydrocodone. It was noted that hydrocodone retained some of its extended-release properties after being finely crushed.
The abuse potential with oral use is significantly lower for intact and finely crushed hydrocodone ER tablets formulated with abuse-deterrence technology compared to hydrocodone IR in nondependent recreational opioid users based on "at the moment" and Overall Drug Liking over 24 hours. Positive, negative, and sedative drug effects were also diminished with intact and finely crushed hydrocodone ER tablets compared with hydrocodone IR. When administered as intended (intact orally), liking scores for hydrocodone ER were similar to those for placebo. The time course of the "at the moment" drug liking profiles for each treatment mimicked its corresponding plasma concentration-time profile. Additionally, assessment of pharmacokinetic parameters for the finely crushed hydrocodone ER tablet showed that it retained some of its ER properties. The reduced dosing frequency and lower abuse potential of this hydrocodone ER tablet may provide a much needed alternative to currently available combination hydrocodone IR products.