Low-dose SoluMatrix diclofenac in the treatment of osteoarthritis: A 1-year, open-label, Phase III safety study

Abstract

Introduction. Diclofenac is used for the treatment of osteoarthritis (OA); however, like other nonsteroidal anti-inflammatory drugs (NSAIDs) it can be associated with serious dose-related adverse events (AEs). Low-dose SoluMatrix® diclofenac has been developed to provide efficacy at lower diclofenac doses. A recently published Phase III study evaluated the efficacy and safety of SoluMatrix diclofenac 35 mg twice daily (b.i.d.) and thrice daily (t.i.d.) in patients with OA pain treated for 12 weeks. Methods. This Phase III multicenter, open-label study assessed the safety of SoluMatrix diclofenac in patients with OA dosed up to 52 weeks (ClinicalTrials.gov: NCT01510912). The study enrolled 602 chronic NSAID/acetaminophen users, aged ≥40 years with OA of the knee or hip. Patients received SoluMatrix diclofenac 35 mg b.i.d., which could be increased to t.i.d. and subsequently reduced to b.i.d. as needed. Safety assessments included AEs, vital signs, physical examination findings, 12-lead electrocardiogram, and clinical laboratory test results. Patient-reported outcomes were evaluated by the Short Form-36 (SF-36). Results. A total of 601 patients received SoluMatrix diclofenac; 373 of 601 patients (62.1%) received treatment for ≥11 months. The most frequent AEs included upper respiratory tract infection, headache, urinary tract infection, diarrhea, nasopharyngitis, and nausea. Serious gastrointestinal, cardiovascular, renal, and hepatic AEs were uncommon. A small proportion (99 patients, 16.5%) of patients discontinued participation in the study due to AEs. Clinically meaningful improvements from baseline in Physical Component Summary Scores of the SF-36 were noted at week 12 and were sustained through week 52. Improvements in six of the eight individual physical and mental SF-36 domains were also noted. Conclusion. SoluMatrix diclofenac treatment for up to 1 year was generally well tolerated in patients with OA pain and associated with improvement in quality of life measures. Trial Registration: www.clinicaltrials.gov identifier: NCT01510912.

Keywords :

• Diclofenac
• osteoarthritis
• pain
• safety
• Short Form-36
• SoluMatrix

Acknowledgments

The authors thank the following individuals: Susan Whitcher, Michael Kuss, Melanie Funke, Daniel Solorio, Claire Sheridan, and the investigators and patients who participated in this study. AlphaBioCom, LLC (King of Prussia, PA, USA), provided editorial support for this manuscript. Funding for editorial support was provided by Iroko Pharmaceuticals, LLC.

Declaration of interest

This study was funded by Iroko Pharmaceuticals, LLC. R. Altman is a consultant to Pfizer, Teva Pharmaceutical Industries Ltd, Petah Tikva, Oletec, Novartis Pharma, and Johnson & Johnson; consultant and member of the speaker’s bureau for Ferring Pharmaceuticals and Iroko Pharmaceuticals, LLC. A. Gibofsky is a stock shareholder of GlaxoSmithKline plc, Bristol-Myers Squibb, Amgen, Pfizer, AbbVie, Regeneron, and Johnson & Johnson; consultant for Takeda, Amgen, AbbVie, Antares, Genentech, Horizon, and Iroko Pharmaceuticals, LLC; and speaker for Amgen, AbbVie, Celgene, Antares, UCB, Pfizer and Iroko Pharmaceuticals, LLC. B. Cryer has served as a consultant for Iroko Pharmaceuticals, LLC, Ritter Pharmaceuticals, Sanofi Pharmaceuticals, Sandoz Pharmaceuticals, and Sucampo, Inc. M.C. Hochberg is a consultant for Iroko Pharmaceuticals, LLC, Amgen, AstraZeneca, Covidien, Eli Lilly and Company, EMD Serono, Genentech Inc., Merck & Co Inc., Novartis Pharma AG, Pfizer, and Pozen Inc. W. E. Hopkins and V. Strand are consultants for Iroko Pharmaceuticals, LLC. J. A. Markenson is a member of the speakers’ bureau of AbbVie, Amgen, Bristol-Myers Squibb, Iroko Pharmaceuticals LLC, Anteres, Pfizer, Celgene, and Janssen and a member of advisory boards for AbbVie, Amgen, Pfizer, and Iroko Pharmaceuticals, LLC. A. Kivitz is a speaker, consultant, and investigator for Iroko Pharmaceuticals, LLC. J. Nezzer is a director of biostatistics at Premier Research. O. Imasogie and C. Young are employees of Iroko Pharmaceuticals, LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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