According to research, a morphine pill with a built-in anti-abuse factor did better than placebo at relieving pain in patients with osteoarthritis.
by Michael Smith, North American Correspondent, MedPage Today
NASHVILLE, Sept. 11 — A morphine pill with a built-in anti-abuse factor did better than placebo at relieving pain in patients with osteoarthritis, researchers said here.
Explain to interested patients that morphine is effective at relieving pain but is controversial in chronic pain because of the potential for abuse.
Note that this study shows a morphine pill that includes a method of reducing the risk of abuse appears to be effective at relieving osteoarthritis pain.
Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Patients taking ALO-01 (Embeda) had a significant improvement (at P=0.0445) in average weekly pain diary scores compared with those taking placebo, according to Joseph Stauffer, D.O., of Alpharma Pharmaceuticals, and colleagues.
The analysis also found that 72.5% of patients taking the drug responded, compared with 57.8% of those on placebo, the researchers reported in a poster at the annual clinical meeting of the American Academy of Pain Management.
Response was defined as more than 30% improvement in pain intensity score from baseline and the difference between the two groups was significant at P=0.005.
The findings come from a randomized, placebo-controlled study, supported by Alpharma, that forms the basis for a new drug application for the medication. The FDA accepted the application Sept. 2 for priority review, the company said.
If it’s approved, Dr. Stauffer said in a statement, it would be “the first opioid medicine to provide a pharmacologic abuse-deterrent feature while effectively treating patients with chronic pain.”
Opioids, such as morphine, are controversial for chronic pain because of the potential for abuse, he said.
To avoid that possibility, Dr. Stauffer said, ALO-01 capsules contain polymer-coated extended-release pellets of morphine sulfate and each has a core of naltrexone (Depade, ReVia), an opioid antagonist.
The idea is that the naltrexone will kick in and reduce the euphoric effects of morphine if the capsule is crushed or chewed. Otherwise, the naltrexone is intended to pass through the body without “clinically meaningful release or accumulation,” according to a company statement.
In the current study, the researchers enrolled 344 adult patients with moderate to severe pain from osteoarthritis of the hip or knee. After up to 14 days of screening and washout, they were titrated to effective pain management levels with ALO-01 in an open-label fashion.
Volunteers were then randomized in a double-blind fashion to either ALO-01 capsules or placebo for 12 weeks.
The main endpoint was mean change in weekly average pain diary score from randomization to the 12-week visit. Responder rate was a secondary efficacy endpoint.
The researchers analyzed the usual adverse events, but also evaluated the possibility of opioid withdrawal using the Clinical Opiate Withdrawal Scale — a clinician assessment of objective signs of withdrawal — and the Subjective Opiate Withdrawal Scale, a self-administered instrument.
For the primary efficacy endpoint, Dr. Stauffer and colleagues reported average weekly pain diary scores increased by 0.3 points for patients on placebo, but fell 0.2 points for those taking ALO-01.
On the Clinical Opiate Withdrawal Scale — which measures withdrawal from zero or none to 48 or severe — the average score was less than one throughout the study in both the placebo and treatment groups, indicating a low risk of opioid withdrawal.
Clinical review of both scales and adverse events “did not detect an increased risk of opioid withdrawal with ALO-01 capsules when taken as directed,” the researchers said.
The drug was generally well tolerated, the researchers said, with adverse events typical of morphine products, such as constipation and nausea.
There’s now a consensus that people with chronic pain should get opioids and the increasing use of such drugs has spawned an increase in abuse, commented Russell Portenoy, M.D., an expert in pain management at Beth Israel Medical Center in New York.
A range of abuse-deterrent drugs is now under development and ALO-01 is the first in the class of chemical deterrent medications, said Dr. Portenoy, who was not involved in the study.
Ironically, he said, they are being developed to curb abuse and to prevent what he called “diversion” — things like drugstore robberies or patients who sell their prescriptions to addicts — but the study presented here doesn’t deal with those issues.
Instead, he said, it shows that the medication works as if it were morphine and did not have the embedded opioid antagonist. “It works,” Dr. Portenoy said. “It’s morphine, who’s surprised?”
But, he added, “we have a public health issue in the rising rate of prescription drug abuse.”
He said abuse-deterrent drugs should be on the market because they have the potential to reduce the chance of an accidental overdose by people trying to get high. A possible consequence of that, he said, would be a reduction in the rate of diversion, as those involved realize the drug has no potential for abuse.
The study was supported by Alpharma Pharmaceuticals, of Bridgewater, N.J., which is developing the drug.
Dr. Stauffer is chief medical officer of the company.
Dr. Portenoy said he participated in a one-day advisory board for Alpharma, offering his views on the clinical acceptability of abuse-deterrent drugs.
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.
Published: September 11, 2008
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