PALM SPRINGS, California — Buprenorphine delivered through a buccal film can relieve chronic low back pain with few adverse effects, a new phase 3 study shows.
"Everything about this drug is really exciting," first author Joseph Gimbel, MD, an orthopedic surgeon and medical director of the Arizona Research Center in Phoenix, told Medscape Medical News.
Dr Gimbel presented the study here at the American Pain Society (APS) 34th Annual Scientific Meeting. The study was funded by the drug's maker, Endo Pharmaceuticals.
A schedule III partial opioid agonist, buprenorphine appears to reach a ceiling for gastrointestinal adverse events, Dr Gimbel reported.
In addition, its pharmacokinetic properties may reduce its risk for abuse, setting it apart from other drugs being described at the meeting, he said. "You won't find anything here that has less chance of addiction."
However, buprenorphine's oral bioavailability is poor, and a transdermal patch has limited dose titration capacity: It does not seem effective in patients needing a morphine sulfate equivalent dose of 80 mg/day.
In a buccal film delivery system, Endo's BioErodible MucoAdhesive, the drug is 46% to 51% bioavailable, said Dr Gimbel.
Endo anticipates action in October by the US Food and Drug Administration on its application to market BioErodible MucoAdhesive buprenorphine for pain requiring around-the-clock, long-term opioid treatment.
To test whether the drug worked for such patients, Dr Gimbel and colleagues recruited 815 patients who were already using opioids to treat moderate to severe chronic low back pain.
They tapered the patients' opioid doses to the equivalent of less than 30 mg morphine sulfate equivalent per day. At that point, the patients rated their pain at a mean of 6.84 on a numeric rating scale from 0 to 10, where 10 is the most intense.
The researchers then provided the patients with the buccal film buprenorphine in a dose that provided adequate analgesia and was generally well tolerated for 14 days. Doses ranged from 150 to 900 μg every 12 hours.
During this titration phase, 304 patients dropped out of the study because of adverse reactions, lack of efficacy, or protocol violations. The mean pain score of the remaining patients fell to 2.88.
Next, the researchers split the remaining patients randomly into two groups: 254 patients continued on buccal film buprenorphine and 257 patients switched to a placebo. The patients did not know which treatment they were getting.
As a rescue medication, they were allowed two doses of one to two tablets of 5 mg hydrocodone and 325 mg acetaminophen for the first 2 weeks. After that they were allowed one dose per day.
Pain rose in both groups during the next 12 weeks, but it increased more in the placebo group than in the buprenorphine group. Rates of adverse events were comparable between the two groups and were generally low for opioid drugs.
Table. Buccal Film Buprenorphine vs Placebo
||Placebo (n = 256)||P Value|
|≥30% pain reduction, %||64||31||<.001|
|≥50% pain reduction, %||40||17||<.001|
|12-week pain increase (numeric rating scale points)||0.88||1.92||<.001|
At the same meeting, another phase 3 trial funded by Endo showed similar results for buccal film buprenorphine in patients with moderate to severe low back pain who had not previously been treated with opioids.
"This is an amazing drug," said Dr Gimbel. "This is one of the few drugs that my patients come back and ask me about."
If it is approved, some physicians may consider buccal film buprenorphine as a replacement for hydrocodone with acetaminophen, said Edward Michna, MD, director of the Pain Trials Center at Brigham and Women's Hospital, Boston, Massachusetts.
And this study makes a good case for the drug, he told Medscape Medical News. "It's hard to treat low back pain," he said.
However, Dr Michna said he has some reservations about buprenorphine in general. In other formulations, it reaches an efficacy ceiling, where higher doses do not achieve more efficacy, he said.
Yet it does have some potential for abuse, he said. "In Europe it's a big drug of abuse," he said. "Are addicts going to be extracting it and injecting it?"
This study was funded by Endo Pharmaceuticals. Dr Gimbel has reported no relevant financial interests. Dr Michna has consulted for Pfizer, Purdue Pharma, and Insys Therapeutics.
American Pain Society (APS) 34th Annual Scientific Meeting: Abstracts 437, 439. Presented May 2013.
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Cite this: Buprenorphine Buccal Film Reduces Chronic Low Back Pain - Medscape - May 19, 2015.