Prescription drug abuse is epidemic, with pain and analgesic prescription medication abuse increasing among all ages, according to statistics gathered from 1965 to 2002 by the National Institute on Drug Abuse (NIDA). The nonmedical use of prescription drugs ranks second only to marijuana as the most prevalent category of drug abuse.

One of the most abused pain management drugs has been oxycodone. According to reports, abusers seeking to defeat the controlled-release effect of the drug crush oxycodone tablets and snort the resulting powder or dissolve it in water or alcohol and inject the solution to attain the immediate "high" resulting from the rapid absorption of the drug. This kind of abuse is associated with several hundred deaths a year in the US.

However, Pain Therapeutics, Inc, has recently reported positive phase III results with Remoxy, a long-acting oxycodone capsule with abuse-resistant properties. Initial tests indicate that crushing or physically manipulating the capsule does not defeat the controlled release of the drug. Since the majority of the oxycodone is bound inside the formulation, Remoxy also resists extraction by acids or alcohol. In fact, data show that freezing, crushing, or submerging Remoxy in high-proof alcohol for hours at a time releases just a fraction of oxycodone compared to that obtained from OxyContin at time points when abusers presumably expect to get high.

Remoxy has been shown to decrease pain and improve quality of life in osteoarthritis (OA) patients with moderate-to-severe chronic pain, compared with placebo. Pain Therapeutics plans to begin an additional phase III study at year end prior to submitting a new drug application with the FDA.

Promising phase III results

In the phase III randomized, double-blinded study, 209 patients from more than 20 clinical sites in the US were randomized to receive 20 mg of Remoxy or matching placebo twice a day over a 4-week study period. Patient demographics and baseline pain scores were similar in both arms.

When compared with OA patients receiving placebo, OA patients taking Remoxy showed a greater decrease in pain scores from baseline to final study based on a standard Likert Pain Scale and also scored better on each component of the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index as well as in measures of physical function, according to a standard SF-12(R) Health Survey and patients' self-reports.

Safety profile similar to traditional opioids

No drug-related safety issues were noted in the phase III trial. Opioid-related adverse events including nausea/vomiting, dizziness, pruritus, and somnolence/sedation were higher in the Remoxy arm compared with placebo. The patient dropout rate was also higher in the Remoxy arm (35%) compared with placebo (24%), mainly due to opioid-related adverse events among Remoxy users. Patients in the placebo arm dropped out mainly due to lack of efficacy, the study showed.

Search for the holy grail continues

While "abuse resistant" formulations may take scientists closer to the holy grail of effective pain relief, a nonaddictive opioid by itself is probably not enough to curb the growing rates of oxycodone abuse and diversion, experts tell CIAOMed.

"We have been trying to develop a nonaddictive opioid in earnest for 60 years," says Frank Vocci, PhD, director of the division of pharmacotherapies and medical consequences of drug abuse at NIDA in Bethesda, Maryland. "Some progress has been made, especially with partial agonists, but the whole idea of an abuse-resistant opiate is still a goal rather than a completed task," he says. Partial agonists include buprenorphine nalbuphine, butorphanol, proxorphan, levallorphan, and nalorphine.

"The bugaboo of the whole thing is that we don't have good treatments for chronic pain; the hope has been that we would develop something as good as opiates at treating pain that didn't have abuse liability," Dr. Vocci explains, adding that all the current drugs have their own issues.

"A formulation that cannot be snorted or injected will help," he admits, noting, however, that a lot of people abuse opioids orally. "Abuse of opioids is increasing, and while sustained release and [formulations] that can't be crushed will be an advance, if people go an oral route, [that] may still [offer] sufficient highs or subjective responses for them to still abuse it."

References

Pain Therapeutics announces positive phase III results [press release]. South San Francisco: Pain Therapeutics, Inc; September 9, 2005. Available at:

http://phx.corporate-ir.net/phoenix.zhtml?c=120834&p=irol-newsArticle&ID=754551&highlight. Accessed September 19, 2005.

Abuse resistant oxycodone clears trial [press release]. In-Pharma Technologist.com; July 7, 2004. Available at:

http://in-pharmatechnologist.com/news/news-ng.asp?id=53367. Accessed September 19, 2005.