Alpharma Inc (BRIDGEWATER, New Jersey), a global specialty pharmaceutical company, announced results from its phase III pivotal efficacy trial that showed ALO-01 (Embeda™) (morphine sulfate extended-release with sequestered naltrexone hydrochloride) capsules provided significant pain relief in patients with moderate-to-severe pain due to osteoarthritis (OA) of the hip or knee compared with placebo. Findings also showed that the capsules were safe and well-tolerated with an overall safety profile consistent with that of other opioid products. If approved by the US FDA, ALO-01 would be the first opioid medicine to provide a pharmacologic abuse-deterrent feature while effectively treating patients with chronic pain. When ALO-01 capsules are taken as directed, the naltrexone passes through the body without clinically meaningful release or accumulation.

The 12-week, double-blind, randomized, placebo-controlled enriched enrollment phase III pivotal trial assessed the effectiveness of the capsules in 344 adult patients. After a screening and washout period ≤14 days from previous treatments, patients were administered two periods of treatment with study drugs: they were first titrated to effective pain management levels with ALO-01 capsules during open-label titration, then they were randomized to double-blind treatment with either ALO-01 capsules or placebo for 12 weeks. Study participants were allowed to use acetaminophen up to 500 mg every 6 hours as a rescue medication. Efficacy assessments included pain intensity scores on the Brief Pain Inventory (BPI), recorded in a subject diary and assessed at in-clinic visits.

According to the study findings, patients who were taking ALO-01 capsules reported significantly more effective pain relief, as measured by mean change in the weekly BPI Average Pain Intensity Score from baseline to the 12-week study endpoint, compared with placebo patients. Additionally, 72.5% of patients reported taking the capsules experienced pain relief of at least 30% from baseline, compared with 57.8% for patients given placebo.

Safety and tolerability included measurements by rates of self-reported adverse events and a measure of opioid withdrawal, an indication of naltrexone leakage from the capsules, called clinical opiate withdrawal scores (COWS). COWS data suggest that naltrexone did not leak out of the capsules and there was no increased risk of opioid withdrawal versus placebo. Adverse events during titration of ALO-01 were constipation (30.5%) and nausea (21.0%); during the 12-week maintenance phase, adverse events for ALO-01and placebo groups, respectively, were diarrhea (12.3% and 12.1%) and nausea (11.7% and 7.5%).

On 2 September 2008, Alpharma announced that the FDA had accepted its New Drug Application (NDA) for ALO-01 capsules for priority review. The priority review status provides for a review period of 6 months from the date of submission. The capsule NDA was submitted on June 30, 2008. Alpharma recently rejected a $1.4 billion takeover bid from King Pharmaceuticals Inc.