Open Access Open Access  Restricted Access Subscription or Fee Access

A randomized, placebo-controlled, double-blinded, parallel-group, 5-week study of buprenorphine transdermal system in adults with osteoarthritis

Catherine Munera, PhD, Margaret Drehobl, MD, Nelson E. Sessler, PharmD, Craig Landau, MD

Abstract


Background: This multicenter, parallel-group, 35-day study in adults with osteoarthritis (OA) pain evaluated the analgesic efficacy and safety of buprenorphine transdermal system (BTDS) designed for 7-day wear.
Methods: Patients with OA pain inadequately controlled with nonsteroidal antiinflammatory drugs or patients who had taken opioids for OA pain within the past year entered a 7-day run-in period during which they took ibuprofen only. Patients with pain ≥7 on a 0-10 scale had their ibuprofen discontinued and were randomized into a 28-day double-blinded period to receive either BTDS at 1 of 3 dose levels (5, 10, or 20 g/h) or placebo. Doses were titrated to effectiveness over a period of 21 days and maintained for 7 days. No rescue medication was allowed during the study. The primary efficacy measure was the proportion of patients who achieved treatment success, defined as a patient satisfaction score of good, very good, or excellent (on day 28 or at early discontinuation) for those who did not discontinue due to ineffective treatment.
Results: More BTDS-treated patients experienced treatment success than placebo TDS-treated patients (44 percent and 32 percent; odds ratio = 1.66, p = 0.036). Fewer patients taking BTDS titrated to the highest dose compared with placebo (p < 0.05). There were two serious adverse events (both in the placebo group) and no deaths. The most common (≥5 percent) adverse events reported in BTDStreated patients were nausea, headache, dizziness, somnolence, application site pruritus, and vomiting.
Conclusion: Compared with placebo, BTDS treatment was effective in treating patients with moderate to severe pain due to OA of the knee or hip. BTDS was welltolerated.

Keywords


buprenorphine, transdermal, pain, analgesia, osteoarthritis, randomized controlled trials

Full Text:

PDF

References


National Center for Chronic Disease Prevention and Health Promotion: Osteoarthritis. Available at http://www.cdc.gov/arthritis/basics/osteoarthritis.htm. Accessed January 6, 2010.

Lawrence RC, Felson DT, Helmick CG, et al.; for National Arthritis Data Workgroup: Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008; 58(1): 26-35.

Berenbaum F: New horizons and perspectives in the treatment of osteoarthritis. Arthritis Res Ther. 2008; 10(Suppl 2): S1.

Xie F, Thumboo J, Li S: True difference or something else? Problems in cost of osteoarthritis studies. Semin Arthritis Rheum. 2007; 37: 127-132.

Buckwalter JA, Saltzman C, Brown T: The impact of osteoarthritis: Implications of research. Clin Orthop Relat Res. 2004: 427(Suppl): S6-S15.

American College of Rheumatology Subcommittee on Osteoarthritis Guidelines: Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 2000; 43(9): 1905-1915.

Pendleton A, Arden N, Dougados M, et al.: EULAR recommendations for the management of knee osteoarthritis: Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2000; 59: 936-944.

Zhang W, Doherty M, Arden N, et al.: EULAR evidence based recommendations for the management of hip osteoarthritis: Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2005; 64: 669-681.

Zhang W, Moskowitz RW, Nuki G, et al.: OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008; 16: 137-162.

Heel RC, Brogden RN, Speight TM, et al.: Buprenorphine: A review of its pharmacological properties and therapeutic efficacy. Drugs. 1979; 17: 81-110.

Johnson RE, Fudala PJ, Payne R: Buprenorphine: Considerations for pain management. J Pain Symptom Manage. 2005; 29(3): 297-326.

Evans HC, Easthope SE: Transdermal buprenorphine. Drugs. 2003; 63(19): 1999-2010.

Bohme K: Buprenorphine in a transdermal therapeutic system—A new option. Clin Rheumatol. 2002; 21 (Suppl 1): S13-S16.

US National Institutes of Health: Safety and efficacy of the buprenorphine transdermal delivery system in subjects with osteoarthritis pain. Available at http://www.clinicaltrials.gov/ct2/show/NCT00314652?id=NCT00314652&rank=1. Accessed October 16, 2009.

ICH Topic E 9: Statistical principles for clinical trials. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. European Medicines Agency Web site. Available at http://www.emea.europa.eu/pdfs/human/ich/036396en.pdf. Accessed August 18, 2009.

ICH Topic E 10: Committee for proprietary medicinal products. Notes for guidance on choice of control groups for clinical trials. European Medicines Agency Web site. Available at http://www.emea.europa.eu/pdfs/human /ich/036496en.pdf. Accessed August 18, 2009.

Committee for Proprietary Medicinal Products: Points to consider on clinical investigation of medicinal products used in the treatment of osteoarthritis. European Medicines Agency Web site. Available at http://www.tga.health.gov.au/docs/pdf/euguide/ewp/078497en.pdf. Accessed August 18, 2009.

Dworkin RH, Turk DC, Farrar JT, et al.: Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005; 113: 9-19.

Food and Drug Administration: Guideline for the Clinical Evaluation of Analgesic Drugs. Rockville, MD: US Department of Health and Human Services, 1992.

Salzman RT, Roberts MS, Wild J, et al.: Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain control? J Pain Symptom Manage. 1999; 18: 271-279.

Parris WCV, Johnson BW, Croghan MK, et al.: The use of controlled-release oxycodone for the treatment of chronic cancer pain: A randomized, double-blind study. J Pain Symptom Manage. 1998; 16: 205-211.

Landau CJ, Carr WD, Razzetti AJ, et al.: Buprenorphine transdermal delivery system in adults with persistent non-cancer-related pain syndromes who require opioid therapy: A multicenter, 5-week run-in and randomized, double-blind maintenance-of-analgesia study. Clin Ther. 2007; 29(10): 2179-2193.

Spyker D, Hale M, Munera C, et al.: Effectiveness and safety of buprenorphine transdermal system (BTDS) compared with hydrocodone/acetaminophen in the treatment of patients with chronic low back pain. J Pain. 2002; 3(2 Suppl 1): 14 Abstr 653.

Steiner D, Munera C, Hale M, et al.: The efficacy and safety of buprenorphine transdermal system (BTDS) in subjects with moderate to severe low back pain: A double-blind study. J Pain. 2009; 10 (Suppl. 1): S51.

Food and Drug Administration: Guidance for industry: Clinical development programs for drugs, devices, and biological products intended for the treatment of osteoarthritis (OA)—Draft guidance. Available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM071577.pdf. Accessed January 6, 2010.

Bove SE, Flatters SJL, Inglis JJ, et al.: New advances in musculoskeletal pain. Brain Res Rev. 2009; 60: 187-201.

Kantor TG, Furst DE: Osteoarthritis. In Max MB, Portenoy RK, Laska EM (eds.): The Design of Analgesic Trials. Philadelphia: Lippincott-Raven Publishers, 1997: 309.




DOI: https://doi.org/10.5055/jom.2010.0017

Refbacks

  • There are currently no refbacks.