Mallinckrodt has reported that a Phase 3 efficacy trial of investigational MNK-155 met the study's primary endpoint of improved pain scores vs. placebo over the first 48 hours following bunionectomy (p<0.001). This difference in pain scores was statistically significant in favor of MNK-155. The data was presented at PAINWeek 2014, a national conference on pain for frontline practitioners, held in Las Vegas, Nevada September 2-6, 2014.

MNK-155 is an investigational extended-release oral formulation of hydrocodone and acetaminophen being studied for the management of moderate to moderately severe acute pain where the use of an opioid analgesic is appropriate. MNK-155 is formulated with both immediate- and extended-release components. The release profile of MNK-155 combines Mallinckrodt-proprietary, patented technology and Depomed's advanced Acuform® drug delivery technology. The NDA for MNK-155 was accepted for review by the U.S. FDA in May 2014 and included results from this study.

"In this study, MNK-155 showed rapid, significant and superior pain relief to placebo with a 12-hour dosing interval throughout the 48-hour study period," said Dr. Mario Saltarelli, Chief Science Officer, Mallinckrodt Pharmaceuticals. "These positive Phase 3 findings are great news as we strive to develop new medications with less frequent dosing for patients with acute pain."

Study Details

The Phase 3 trial was a multicenter, randomized, double-blind, placebo-controlled, parallel-arm study comparing the efficacy and safety of MNK-155 and placebo in 403 patients with moderate to moderately severe acute pain following a unilateral first metatarsal bunionectomy. Subjects received a single 3-tablet loading dose of MNK-155 (7.5 mg hydrocodone and 325 mg acetaminophen tablets; 22.5 mg/975 mg total dose), followed by 2 tablets every 12 hours (15 mg /650 mg total dose) over 48 hours or placebo. Rescue ibuprofen up to 400 mg every 4 hours was allowed for both the MNK-155 and placebo arms.

The primary endpoint was the summed pain intensity difference (change in pain from baseline) over 48 hours (SPID48). Secondary measures included: Cumulative SPID at 0-4, 0-8, 0-12, 0-24, and 0-36 hours; mean PID beginning 15 minutes after dosing, mean total pain relief (TOTPAR) for the time periods 0-4, 0-8, 0-12, 0-24, 0-36, and 0-48 hours; and time to perceptible, confirmed, and meaningful pain relief. The most common adverse events associated with the use of MNK-155 were nausea, dizziness, vomiting, headaches, constipation, pruritus and somnolence (sleepiness).