New Orleans—A unique formulation of an extended-release oxycodone plus sequestered naltrexone (an opioid antagonist), ALO-02, may deliver safety and efficacy for pain control and also mitigate the drug “high” from tampering with the capsule (e.g., crushing) that often occurs with abuse of prescription opioids. The compound is currently in Phase III of testing.
“We are one of the first companies to advance this technology as an abuse deterrent. Each pellet within each capsule contains oxycodone and a sequestered core of naltrexone. The naltrexone is not intended to be released if the capsule is taken as prescribed. But if a person tries to manipulate the capsule by crushing it, naltrexone is released, possibly reducing the analgesic and euphoric effects of oxycodone. This may mitigate the quick high,” said Kenneth Sommerville, MD, vice president, Clinical Sciences, Pfizer Pharmaceuticals Inc.
At the 2013 annual meeting of the American Pain Society, Dr. Sommerville and his colleagues presented the first report of safety data from a 12-month, open-label, single-arm study that included a total of 395 adult patients with moderate to severe, chronic noncancer pain (abstract 414).
Doses of ALO-02 could be adjusted upward or downward; the total daily dose range was 20 to 160 mg of oxycodone. A total of 193 patients (48.9%) received ALO-02 for at least 181 days and 105 patients (26.6%) were treated with the drug for more than 361 days.
Although the trial was not designed to show efficacy, the analgesic effects of oxycodone were evident over time. Pain scores improved over the course of the study, and withdrawal was not induced by the naltrexone component of the formulation. Dr. Sommerville said withdrawal occurred in one patient and that patient did not take the medication correctly.
Adverse events (AEs) of the innovative drug were similar to those reported of other opioids. The most common treatment-emergent AEs were nausea (25.3%), constipation (21.3%), vomiting (13.9%) and headache (11.6%). The most commonly reported treatment-related AEs included constipation (18%), nausea (14.9%), somnolence (8.4%), fatigue (6.8%), dizziness (5.6%) and vomiting (5.1%). The most common treatment-emergent serious AEs, each seen in 0.5% of patients, were acute myocardial infarction, noncardiac chest pain, pneumonia, convulsion and nephrolithiasis.
The treatment discontinuation rate was 60%, which is similar to other long-term opioid trials, according to Dr. Sommerville. The two most common AEs leading to discontinuation were nausea (4.6%) and constipation (2.5%).
Efficacy data are not yet available from an ongoing double-blind, placebo-controlled trial of ALO-02.
Commenting on this study, Nathaniel Katz, MD, president of Analgesic Solutions and adjunct assistant professor of anesthesia at Tufts University School of Medicine in Boston, said ALO-02 is an example of one of two approaches for abuse deterrents. The first approach is a physicochemical barrier, making it more difficult to crush or dissolve the pill or capsule. “All currently marketed abuse deterrents, including extended-release tapentadol [Nucynta, Johnson & Johnson] and reformulated OxyContin [Purdue Pharma], are based on this,” Dr. Katz said.
The second approach is to combine an opioid with an antagonist that becomes active only when the drug is tampered with. One such drug, Embeda, a morphine/naltrexone formulation, was on the market but was voluntarily recalled by Pfizer in 2011, due to insufficient product stability. (Pfizer currently is pursuing options for reintroducing it, according to Dr. Sommerville.) ALO-02 is the second drug based on this principle.
“It is not clear which approach will work better or whether both approaches will be effective. The jury is out on approach No. 1; the second approach may work better. It is challenging to figure out how to defeat abuse. In general, my sense is abuse deterrents will reduce abuse, and the marketplace will tell us which approach works best,” Dr. Katz said.