Comparison of subjective effects of extended-release versus immediate-release
oxycodone/acetaminophen tablets in healthy nondependent recreational users of
prescription opioids: a randomized trial.
Author(s): Morton T(1), Kostenbader K, Montgomery J, Devarakonda K, Barrett T, Webster L.
Affiliation(s): Author information:
(1)Senior Principal Pharmacokinetic Scientist, PRA Healthsciences, Salt Lake City,
UT.
Publication date & source: 2014, Postgrad Med. , 126(4):20-32
BACKGROUND: Prescription opioids have substantial abuse potential. This study
compared the positive subjective drug effects of a newly developed
extended-release (ER) oxycodone (OC)/acetaminophen (acetyl-para-aminophenol
[APAP]) formulation with those of immediate-release (IR) OC/APAP.
METHODS: This randomized, double-blind, active- and placebo-controlled, 7-way
crossover study enrolled healthy volunteers who were recreational prescription
opioid users. The protocol was approved by an institutional review board and all
participants provided written informed consent. Participants received single
doses of intact ER and IR OC/APAP 15/650 mg, intact ER and IR OC/APAP 30/1300 mg,
crushed ER and IR OC/APAP 30/1300 mg, and placebo. Peak subjective effects
(Emax), time to Emax, and area under the drug-effect curves for drug liking, drug
high, and good drug effects were measured using visual analogue scales. Least
squares means with 95% confidence interval were compared using analysis of
variance.
RESULTS: Among completers (N = 55), intact ER OC/APAP produced delayed and lower
peak effects versus IR OC/APAP. Comparing intact tablets, the drug liking Emax
(least squares means [95% confidence interval]) was significantly lower for
OC/APAP 30/1300 mg (76.4 [72.8 to 80.0]) than for IR OC/APAP 30/1300 mg (85.6
[81.9 to 89.2]; difference, -9.2 [-13.1 to -5.2]; P < 0.001). Similar results
were observed for intact ER and IR OC/APAP (15 mg/650 mg). Crushing ER OC/APAP
30/1300 mg further delayed these effects compared with the same dose of crushed
IR OC/APAP and intact ER OC/APAP.
CONCLUSIONS: Extended-release OC/APAP produced lower subjective drug effects than
IR OC/APAP. Crushing ER OC/APAP further delayed onset of subjective effects
compared with intact ER OC/APAP. The ER OC/APAP may be less attractive for abuse
than IR OC/APAP.
CLINICAL TRIAL REGISTRATION: This phase 1 study conducted in the United States
was not registered.
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