title: Civamide cream 0.075% in patients with osteoarthritis of the knee: a 12-week randomized controlled clinical trial with a longterm extension.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of civamide cream 0.075% for the treatment of osteoarthritis (OA) of the knee.
  
  
  METHODS
  We conducted a 12-week, multicenter, randomized, double-blind study with a 52-week open-label extension. Patients with OA of the knee received either civamide cream 0.075% or a lower dose of civamide cream, 0.01%, as the control. The 3 co-primary endpoints in the double-blind study were the time-weighted average (TWA) of change from baseline to Day 84 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, the WOMAC physical function subscale, and the Subject Global Evaluation (SGE). In the 52-week open-label extension study, the Osteoarthritis Pain Score and SGE were assessed.
  
  
  RESULTS
  A total of 695 patients were randomized to receive civamide cream 0.075% (n = 351) or civamide cream 0.01% (control; n = 344) in the double-blind study. Significance in favor of civamide cream 0.075% was achieved for the TWA for all 3 co-primary efficacy variables: WOMAC pain (p = 0.009), WOMAC physical function (p < 0.001), and SGE (p = 0.008); and at Day 84 for these 3 variables (p = 0.013, p < 0.001, and p = 0.049, respectively). These analyses accounted for significant baseline-by-treatment interactions. In the 52-week open-label extension, efficacy was maintained. Civamide cream 0.075% was well tolerated throughout the studies.
  
  
  CONCLUSIONS
  These studies demonstrate the efficacy of civamide cream for up to 1 year of continuous use. Civamide cream, with its lack of systemic absorption, does not have the potential for serious systemic toxicity, in contrast to several other OA treatments.
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schnitzer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pelletier
authors.forename: Doug M
authors.initials: DM
authors.lastname: Haselwood
authors.forename: William T
authors.initials: WT
authors.lastname: Ellison
authors.forename: John E
authors.initials: JE
authors.lastname: Ervin
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gordon
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Lisse
authors.forename: W Tad
authors.initials: WT
authors.lastname: Archambault
authors.forename: Allan R
authors.initials: AR
authors.lastname: Sampson
authors.forename: Heidi B
authors.initials: HB
authors.lastname: Fezatte
authors.forename: Scott B
authors.initials: SB
authors.lastname: Phillips
authors.forename: Joel E
authors.initials: JE
authors.lastname: Bernstein
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D002211:Capsaicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000503:physiopathology*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: C117479:zucapsaicin; D002211:Capsaicin