Efficacy and Safety of Piroxicam Patch versus Piroxicam Cream in Patients with Lumbar Osteoarthritis

Abstract

In order to assess the efficacy and safety of a new patch containing 14 mg of Piroxicam (CAS 36322–90-4) 1%, applied once daily, in comparison with a reference marketed formulation, piroxicam 1% cream applied three times a day, placebo patch applied once daily, a randomized, placebo-controlled, parallel-group clinical trial was carried out by general practitioners in patients with lumbar osteoarthritis aged between 18 and 75 years. Pain during daily activities scored on a 100 mm visual analogue scale was the primary outcome measure. Other secondary outcome measures were pain on isometric contraction, on full passive motion, and on pressure, and functional disability. Statistical analysis was performed on the differences between the three groups in the intention-to-treat population (ITT).

One hundred and eighty patients were enrolled. The available ITT population comprised 179 patients. The compliance was very good. Decrease in pain score during daily activities after the eight days of study treatment (at the final visit, V_f) was 42.2%, 41.7% and 25.8% in the piroxicam patch, piroxicam cream and placebo groups, respectively. The difference between the pain scores in two active treatments arms was not statistically sig-

nificant at the V_f whereas the differences between the pain scores of two active treatment arms vs the placebo arm were statistically significant validating the study design.

All efficacy measures improved during the study, for both the active treatment groups, and the results for the secondary efficacy variables were generally consistent with those concerning the main efficacy criterion.

The difference between the two active treatments in pain during daily activities were statistically significant at the final visit; in fact the 95% CI of the difference between the mean of responder rate of the piroxicam patch and piroxicam cream was −18.3%, +24.4% indicating a trend of superiority of the piroxicam patch versus the cream (per-protocol analysis).

The data obtained during the intermediate visit (V₂, day 4) allow us to assess that the piroxicam patch was on average better than the piroxicam cream in terms of fast pain reduction (change from baseline:–29.1% for piroxicam patch in comparison to −24.6% for piroxicam cream). Moreover the piroxicam patch proved to be on average more effective than the piroxicam cream in terms of secondary efficacy endpoints. Safety was considered satisfactory in all groups.

Conclusions:

The piroxicam patch is effective in the treatment of lumbar osteoarthritis and has demonstrated to be well tolerated and it improves patients compliance. The piroxicam patch offers a comparable alternative to the marketed piroxicam cream for the treatment of lumbar osteoarthritis with the advantage of a better compliance with the once a day application of the patch compared to three daily applications for the piroxicam cream.

Key words

CAS 36322–90-4 - Lumbar osteoarthritis - Non-steroidal anti-inflammatory drug (NSAID), patch - Piroxicam, efficacy, safety

• References

• 1 Zizic TM, Sutton JD, Stevens MB. Long term experience with piroxicam in osteoarthritis. Semin Arthritis Rheum. 1985; 14: 14-9
• 2 Meisel AD. Clinical benefits and comparative safety of piroxicam. Am J Med. 1986; 81 (Suppl 5B) 15-21
• 3 Rasetti-Escargueil C, Grangé V. Pharmacokinetic profiles of two tablet formulations of piroxicam. Int J Pharm. 2005; 295: 129-34
• 4 Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. BMJ. 2004; 329-324
• 5 Huskisson EC. Measurement of pain. J Rheumatol. 1982; 9: 768-9
• 6 World Medical Association Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subject. 52nd WMA General Assembly, Edinburgh (Scotland); October 2000.
• 7 The European Agency for the Evaluation of Medicinal Products. Note for Guidance on Good Clinical Practice. July 2002 CPMP/ICH/135/95.
• 8 Lee JS, Hobden E, Stiell IG, Wells GA. Clinically important change in the visual analog scale after adequate pain control. Acad Emerg Med. 2003; 10 (10) 1128-30
• 9 Cepeda MS, Africano JM, Polo R, Alcala R, Carr DB. What decline in pain intensity is meaningful to patients with acute pain? Pain. 2003; 105 (l–2) 151-7
• 10 Guidance for Industry. Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products. U.S. Department of Health and Human Services, Food and Drug Administration; May 1998.
• 11 The European Agency for the Evaluation of Medicinal Products. Points to consider on switching between superiority and non-inferiority. London, 27 July 2000 CPMP/EWP/482/99.
• 12 The European Agency for the Evaluation of Medicinal Products. Note for guidance on statistical principles for clinical trials. September 1998 CPMP/ICH/363/96.
• 13 Newcombe RG. Interval estimation for the difference between different proportions: comparison of eleven method. Statist Med. 1998; 17: 873-90
• 14 Newcombe RG, Altman DG. Proportions and their differences. In: Altman DG, D. Machin, Bryant TN, Gardner MJ, editors. Statistics with Confidence. 2nd ed. London: BMJ Books; 2000.