title: The gastrointestinal tolerability of the LOX/COX inhibitor, licofelone, is similar to placebo and superior to naproxen therapy in healthy volunteers: results from a randomized, controlled trial.
abstract: OBJECTIVE
  Concerns exist over the safety of conventional nonsteroidal antiinflammatory drugs (NSAIDs) and selective cyclooxygenase (COX)-2 inhibitors. In experimental models, licofelone, a competitive inhibitor of 5-lipoxygenase (5-LOX) and COX-1/-2, has been shown to have good gastrointestinal and general tolerability and analgesic and antiinflammatory properties. The aim of the present endoscopy trial was to investigate the gastroduodenal tolerability of licofelone compared to placebo and naproxen in healthy volunteers.
  
  
  METHODS
  In this randomized, parallel-group trial, healthy volunteers received licofelone 200 mg b.i.d. (n = 30), licofelone 400 mg b.i.d. (n = 30), naproxen 500 mg b.i.d. (n = 30), or placebo (n = 31). Tolerability was assessed by gastro/duodenoscopy following 4 wk of treatment. Laboratory parameters and the incidence of ulcers and adverse events were recorded.
  
  
  RESULTS
  Ulcers were observed in 20% of the naproxen-treated volunteers, compared with 0% of those receiving licofelone 200 mg, licofelone 400 mg, and placebo (p= 0.024). Posttreatment mean gastric Lanza scores were similar for volunteers who received placebo or either dose of licofelone, while Lanza scores were significantly worse following naproxen therapy (p < 0.00001). The gastric mucosa was normal in 93%, 89%, and 90% of volunteers who received licofelone 200 mg, licofelone 400 mg, or placebo, respectively, compared with 37% of volunteers receiving naproxen. The incidence of adverse events did not differ significantly between licofelone 200 mg or naproxen therapy. No clinically relevant changes in laboratory parameters were observed with licofelone or naproxen therapy.
  
  
  CONCLUSIONS
  The results from this trial indicate that licofelone has a potential gastrointestinal safety advantage over conventional NSAID therapy, as licofelone was associated with significantly superior gastric tolerability and a lower incidence of ulcers compared with naproxen in healthy volunteers. Further trials will be required to investigate the safety and efficacy of licofelone in the treatment of diseases such as osteoarthritis.
authors.affiliation: Pharos Contract Research, Ulm, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bias
authors.forename: Anton
authors.initials: A
authors.lastname: Buchner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Klesser
authors.forename: Stefan
authors.initials: S
authors.lastname: Laufer
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000328:Adult; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004384:Duodenoscopy; D004386:Duodenum / Q000187:drug effects / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D005773:Gastroscopy; D006801:Humans; D015994:Incidence; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D016859:Lipoxygenase Inhibitors; D008297:Male; D009288:Naproxen / Q000627:therapeutic use*; D010437:Peptic Ulcer / Q000139:chemically induced / Q000453:epidemiology; D011758:Pyrroles / Q000627:therapeutic use*
chemical_list: D000085:Acetates; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011758:Pyrroles; D009288:Naproxen; C088092:licofelone