Randomized clinical trial evaluating transdermal Ibuprofen for moderate to severe knee osteoarthritis

• Published in: Pain physician 2013-11, Vol.16 (6), p.E749-E762
• Main Authors: Varadi, Gyula, Zhu, Zhen, Blattler, Thomas, Hosle, Manfred, Loher, Alfons, Pokorny, Rolf, Frey, Diana, Carter, Stephen G
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Arthritis; Clinical trials; Double-Blind Method; Female; Humans; Ibuprofen - administration & dosage; Male; Middle Aged; Nonsteroidal anti-inflammatory drugs; Osteoarthritis; Osteoarthritis, Knee - drug therapy; Pain Measurement; Patient satisfaction
• ISSN: 1533-3159; 2150-1149
• DOI: 10.36076/ppj.2013/16/E749

Osteoarthritis is a common condition, typically treated with orally administered analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Chronic administration of NSAIDs, serotonin-norepinephrine reuptake inhibitors (SNRIs, i.e., duloxetine), and opioid medications (i.e., tramadol) is regularly associated with multiple, serious side effects, in part due to the route of administration. Transdermal delivery of NSAIDs, such as ibuprofen, represents a potentially alternative treatment for this inflammatory pain condition with a better therapeutic profile. Investigate the safety and efficacy of a novel transdermal ibuprofen formulation (VALE®-ibuprofen) containing 10% ibuprofen, compared to a placebo in a randomized, double-blinded clinical trial, for clinical improvement in patients with moderate to severe painful osteoarthritis of the knee. A randomized, placebo-controlled, double blind, multi-center Phase 2 clinical trial. An academic medical center, and private rheumatology and interventional pain management practices. The Phase 2 clinical study included patients with primary osteoarthritis in a single knee joint with a progression level of moderate to severe based in part on a grade II or III designation according to the Kellgren and Lawrence classification system. Patients received the corresponding, randomly assigned study formulation (VALE-ibuprofen or placebo) for application to the target knee at a dose of 2.0 grams of drug product (200 mg ibuprofen) twice daily for 14 days. The evaluation of the efficacy of the treatments utilized the widely accepted methods of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index and the Visual Analog Scale (VAS) scores for the patients. The results indicate that the transdermal VALE-ibuprofen formulation was very well tolerated from a safety perspective during the 2-week trial and also produced significant, positive clinical improvements superior to the placebo in all clinical endpoints tested. In particular, the WOMACTotal and WOMACPhysical Functioning, for the VALE-ibuprofen, were superior compared to the placebo (P = 0.0283 and P = 0.0201, respectively). Other clinical endpoints including the WOMACPain, WOMACStiffness, and VASResting scores were superior to those obtained from the placebo group, trending towards statistical significance compared to placebo (P = 0.0811, 0.1103, and 0.0785, respectively). Based on the Patient and Physician Global Impression of Change survey, patient sat