A randomized, double-blind, placebo-controlled study of the efficacy and safety of MNK-795, a dual-layer, biphasic, immediate-release and extended-release combination analgesic for acute pain

Abstract

Objective:

To investigate the efficacy and safety of a bilayer combination oxycodone (OC) and acetaminophen (APAP) analgesic with both immediate-release and extended-release (ER) components (OC/APAP ER) in patients with moderate to severe pain using an established acute pain model.

Research design and methods:

This was a randomized, double-blind, placebo-controlled trial. Adult patients were included in the study if they had a pain intensity score ≥4 on a 0–10 numerical rating scale after bunionectomy surgery, and were randomized (1:1) to receive four doses (two tablets q12h) of OC/APAP ER or placebo.

Clinical trial registration:

ClinicalTrials.gov identifier: NCT01484652.

Main outcome measures:

The primary efficacy endpoint was the summed pain intensity difference over the first 48 hours (SPID₄₈). Secondary endpoints included SPIDs and total pain relief (TOTPAR) over the dosing intervals; time to perceptible, meaningful, and confirmed pain relief; and the proportion of patients with ≥30% reduction in pain intensity scores.

Results:

A total of 329 patients were enrolled, of whom 266 (OC/APAP ER, n = 135; placebo, n = 131) completed the study. The mean (SE) SPID₄₈ was 114.9 (7.6) in the OC/APAP ER group and 66.9 (7.6) in the placebo group (P < 0.0001). SPID and TOTPAR values were significantly greater with OC/APAP ER than with placebo over all time periods analyzed, and the median times to perceptible, meaningful, and confirmed pain relief were significantly shorter. More patients showed ≥30% reduction in pain intensity scores with OC/APAP ER than with placebo at all times after 0.5 hours. OC/APAP ER was generally well tolerated. A limitation of this study was the lack of an active comparator.

Conclusions:

OC/APAP ER was efficacious and generally well tolerated in an established model of moderate to severe acute pain, providing an onset of analgesia in approximately 30 minutes and sustained pain relief over the 12 hour dosing period.

Keywords::

• Acute pain
• Bunionectomy
• Efficacy
• Opioid analgesic
• Pain intensity
• Pain relief

Transparency

Declaration of funding

This study was funded by Mallinckrodt Inc.

Declaration of financial/other relationships

N.S. received grants as a clinical investigator from Mallinckrodt Inc. T.B., L.S., J.Y., and M.G. are employees of Mallinckrodt Inc. K.K. is a paid consultant to Mallinckrodt Inc.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

Technical editorial and medical writing support for the development of this manuscript was provided by Michael Shaw PhD and Traci Stuve MA, Synchrony Medical Communications, LLC, West Chester, PA, USA. Funding for this support was provided by Mallinckrodt Inc., Hazelwood, MO, USA.

Previous presentation: Poster presented at PAINWeek 2013, 4–7 September 2013, Las Vegas, NV, USA.

Notes

*Percocet is a registered trade name of Endo Pharmaceuticals, Chadds Ford, PA, USA

†Vicodin is a registered trade name of AbbVie Inc., North Chicago, IL, USA

‡Acuform is a registered trade name of Depomed, Inc., Newark, CA, USA