The ACTION study: A randomized, open-label, multicenter trial comparing once-a-day extended-release morphine sulfate capsules (AVINZA®) to twice-a-day controlled-release oxycodone hydrochloride tablets (OxyContin®) for the treatment of chronic, moderate to severe low back pain

Richard L. Rauck, MD; Stephen A. Bookbinder, MD; Timothy R. Bunker, MD; Christopher D. Alftine, MD; Richard Ghalie, MD; Andres Negro-Vilar, MD, PhD; Egbert de Jong, MD; Steven Gershon, MD

doi:10.5055/jom.2006.0025

Authors

Richard L. Rauck, MD
Stephen A. Bookbinder, MD
Timothy R. Bunker, MD
Christopher D. Alftine, MD
Richard Ghalie, MD
Andres Negro-Vilar, MD, PhD
Egbert de Jong, MD
Steven Gershon, MD

DOI:

https://doi.org/10.5055/jom.2006.0025

Keywords:

AVINZA, OxyContin, chronic low back pain

Abstract

This large, open-label, randomized, parallel-group, multicenter study compared two oral sustained-release opioids (SROs)—AVINZA® (A-MQD), morphine sulfate extended-release capsules given once a day, and OxyContin® (O-ER), oxycodone modified-release tablets given twice a day—in SRO-naive subjects ages 30 to 70 with chronic, moderate to severe low back pain. Of the 392 subjects enrolled and randomized, 266 (132 in the AMQD group and 134 in the O-ER group) completed the opioid dose titration phase and entered an eight-week evaluation phase. During the evaluation phase, A-MQD achieved significantly better pain control than O-ER, as demonstrated by a greater decrease from baseline in pain scores obtained four times daily during weeks one, four, and eight (p = 0.002). The number of breakthrough-pain rescue medication doses adjusted for the number of patient days was significantly lower in the A-MQD group (p < 0.0001). Better pain control with A-MQD was achieved with a significantly lower daily opioid dose than with O-ER (mean 69.9 mg and 91 mg morphine equivalents, respectively; p = 0.0125). Quality of sleep was significantly better with A-MQD for the entire evaluation phase (p = 0.0026). The incidence and severity of elicited opioid side effects were similar in the two groups. This trial demonstrated that once-daily A-MQD provides consistent around-the-clock pain relief in patients with low back pain. In patients who completed opioid dose titration, A-MQD was significantly better than O-ER for reducing pain and improving sleep, while requiring a lower daily opioid dose.

Author Biographies

Richard L. Rauck, MD

Carolinas Pain Institute, Winston-Salem, North Carolina.

Stephen A. Bookbinder, MD

Ocala Rheumatology Research Center, Ocala, Florida.

Timothy R. Bunker, MD

The Birmingham Pain Center, Birmingham, Alabama.

Christopher D. Alftine, MD

Medford Medical Clinic, Medford, Oregon.

Richard Ghalie, MD

Ligand Pharmaceuticals Inc., San Diego, California.

Andres Negro-Vilar, MD, PhD

Ligand Pharmaceuticals Inc., San Diego, California.

Egbert de Jong, MD

Organon Pharmaceuticals USA Inc., Roseland, New Jersey.

Steven Gershon, MD

Advanced Pain Management and Rehabilitation PC, Virginia Beach, Virginia.

References

American Pain Society: Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain. Glenview: American Pain Society; 2003.

Gallup Organization (for Merck and Co., Inc.): Pain in America: A Research Report. New York: Ogilvy Public Relations, 2000.

Andersson G: Epidemiological features of chronic low-back pain. Lancet. 1999; 354: 581-585.

Luo X, Pietrobon R, Sun SX, et al.: Estimates and pattern of direct health care expenditures among individuals with back pain in the United States. Spine. 2004; 29: 79-86.

Chou R, Clark E, Helfand M: Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: A systematic review. J Pain Symptom Manage. 2003: 26: 1026-1048.

Desphande AA, Atlas S, Furlan AD, et al.: Opioids for chronic low back pain. The Cochrane Database of Systematic Reviews 4. Art. no. CD004959, 2004.

Kalso E, Edwards JE, Moore RA, et al.: Opioids in chronic noncancer pain: Systematic review of efficacy and safety. Pain. 2004; 112: 372-380.

McNicol E, Horowicz-Mehler N, Fisk RA, et al.: Management of opioid side effects in cancer-related and chronic non-cancer pain: A systematic review. J Pain. 2003; 4: 231-2567.

Watson CP, Watt-Watson JH, Chipman ML: Chronic noncancer pain and the long term utility of opioids. Pain Res Manag. 2004; 9: 19-24.

Caldwell JR, Rapoport RJ, Davis JC, et al: Efficacy and safety of a once-daily morphine formulation in chronic, moderate-tosevere osteoarthritis pain: results from a randomized, placebocontrolled, double-blind trial and an open-label extension trial. J Pain Symptom Manage. 2002;23(4):278-291.

Portenoy RK, Sciberras A, Eliot L, et al.: Steady-state pharmacokinetics comparison of a new, extended-release, once-daily morphine formulation, AVINZA, and a twice-daily controlled-release morphine formulation in patients with chronic moderate-to-severe pain. J Pain Symptom Manage. 2002; 23(4): 292-300.

Mandema JW, Kaiko RF, Oshlack B, et al.: Characterization and validation of a pharmacokinetic model for controlledrelease oxycodone. Br J Clin Pharmacol. 1996; 42: 747-756.

Hale ME, Fleischmann R, Salzman R, et al.: Efficacy and safety of controlled-release versus immediate-release oxycodone: Randomized, double-blind evaluation in patients with chronic back pain. Clin J Pain. 1999; 15: 179-183.

Eliot L, Geiser R, Loewen G: Steady-state pharmacokinetic comparison of a new, once-daily, extended-release morphine formulation (Morphelan™) and Oxycontin® twice daily. J Oncol Pharm Practice. 2001; 7: 1-8.

Keller S, Bann CM, Dodd SL, et al.: Validity of the brief pain inventory for use in documenting the outcomes of patients with non-cancer pain. Clin J Pain. 2004; 20: 309-318.

Buysse DJ, Reynolds CF III, Monk TH, et al.: Quantification of subjective sleep quality in healthy elderly men and women using the Pittsburgh Sleep Quality Index (PSQI). Sleep. 1991; 14: 331-338.

Rauck R, Bookbinder S, Bunker T, et al.: Randomized multicenter study of oral once-a-day AVINZA (morphine sulfate extended-release capsules) vs. twice-daily OxyContin (oxycodone hydrochloride controlled-release) for the treatment of chronic moderate-to-severe low back pain. J Pain. 2005; 6(suppl. 1, abstr. 747).

Rauck R, Bookbinder S, Bunker T, et al.: Randomized multicenter, open-label extension (Part II) to the ACTION Trial (AVINZA vs. OxyContin Trial in opioid-naive patients) for the treatment of chronic moderate to severe low back pain. Proced Am Acad Pain Med: annual meeting. Poster #54. 2006

Hale M, Dvergsten C, Gimbel J: Efficacy and safety of oxymorphone extended release in chronic low back pain: Results of a randomized, double-blind, placebo-controlled and activecontrolled Phase III study. J Pain. 2005; 6: 21-28.

Hale MF, Rauck R, Ma T, et al.: Open-label titration of oxymorphone extended release in opioid-experienced patients with chronic low back pain. Proced Am Acad Pain Med: annual meeting. Poster #138. 2006.

Markenson JA, Croft J, Zhang PG, et al.: Treatment of persistent pain associated with osteoarthritis with controlledrelease oxycodone tablets in a randomized controlled clinical trial. Clin J Pain. 2005; 21: 524-535.

Marcus DA, Glick RM: Sustained-release oxycodone dosing survey of chronic pain patients. Clin J Pain. 2004; 20: 363-366.

Rosenthal M, Spinweber C, Dziewanowska Z, et al.: Once-aday AVINZA® effects on sleep quality measurements (polysomnographic and subjective) in patients treated for chronic moderate and sever osteoarthritis (OA) pain. American Pain Society: annual meeting. Poster #746. 2005.