title: Randomized clinical trial evaluating transdermal Ibuprofen for moderate to severe knee osteoarthritis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  A randomized, placebo-controlled, double blind, multi-center Phase 2 clinical trial.
  
  
  METHODS
  An academic medical center, and private rheumatology and interventional pain management practices.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 satisfaction slightly improved across both groups; however, no statistical significance was detectable as compared to the baseline.
  
  
  CONCLUSIONS
  The sample size of 64 subjects in the final data analysis and the lack of including an orally administered drug group are limitations of this study.
  
  
  CONCLUSIONS
  The use of transdermal VALE-ibuprofen has beneficial clinical effects on the pain levels experienced in some patients with moderate to severe osteoarthritis of the knee as measured by the WOMAC Osteoarthritis Indices for stiffness, pain, physical function, and total. Visual Analog Scales (VAS) tests, VASMotion and VASWeight-bearing, again while appeared superior to placebo, were not statistically different from placebo.
  
  
  BACKGROUND
  NCT01496326.
authors.affiliation: BioChemics and Alterix Inc., Dept. of Research and Development, Danvers, MA.
authors.forename: Gyula
authors.initials: G
authors.lastname: Varadi
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhu
authors.forename: Thomas
authors.initials: T
authors.lastname: Blattler
authors.forename: Manfred
authors.initials: M
authors.lastname: Hosle
authors.forename: Alfons
authors.initials: A
authors.lastname: Loher
authors.forename: Rolf
authors.initials: R
authors.lastname: Pokorny
authors.forename: Diana
authors.initials: D
authors.lastname: Frey
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Carter
mesh_terms: D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010147:Pain Measurement
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen