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Ann Rheum Dis 72:187-195 doi:10.1136/annrheumdis-2012-202239
  • Clinical and epidemiological research
  • Extended report

A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee

  1. Eric Vignon7
  1. 1Primary Care Medicines Development Group, Pfizer Inc, Groton, Connecticut, USA
  2. 2Department of Radiology, Virginia Commonwealth University Health System, Richmond, Virginia, USA
  3. 3Department of Rheumatology, Kansas University Medical Center, Kansas City, Kansas, USA
  4. 4Division of Rheumatology, New York School of Medicine, New York, New York, USA
  5. 5Vasculox, Inc, St Louis, Missouri, USA
  6. 6Department of Medical Affairs, BioClinica, Inc., Newtown, Pennsylvania, USA
  7. 7Claude Bernard University, Lyon, France
  1. Correspondence to Dr Marie-Pierre Hellio Le Graverand, Medicines Development Group, Primary Care Business Unit, Pfizer Inc., 445 Eastern Point Road, Groton, CT 06340, USA; helliomp{at}pfizer.com
  • Accepted 21 October 2012
  • Published Online First 10 November 2012

Abstract

Objective To determine if inhibition of inducible nitric oxide synthase (iNOS) with cindunistat hydrochloride maleate slows progression of osteoarthritis (OA)

Methods This 2-year, multinational, double-blind, placebo-controlled trial enrolled patients with symptomatic knee OA (Kellgren and Lawrence Grade (KLG) 2 or 3). Standard OA therapies were permitted throughout. Patients were randomly assigned to cindunistat (50 or 200 mg/day) or placebo. Randomisation was stratified by KLG. Radiographs to assess joint space narrowing (JSN) were acquired using the modified Lyon-schuss protocol at baseline, week 48 and 96.

Results Of 1457 patients (50 mg/day, n=485; 200 mg/day, n=486; placebo, n=486), 1048 (71.9%) completed the study. Patients were predominantly women; 56% had KLG3. The primary analysis did not demonstrate superiority of cindunistat versus placebo for rate of change in JSN. In KLG2 patients, JSN after 48 weeks was lower with cindunistat 50 mg/day versus placebo (p=0.032). Least-squares mean±SE JSN with cindunistat 50 mg/day ( −0.048±0.028 mm) and 200 mg/day (−0.062±0.028 mm) were 59.9% (95% CI 6.8% to 106.9%) and 48.7% (95% CI -8.4% to 93.9%) of placebo, improvement was not maintained at 96 weeks. No improvement was observed for KLG3 patients at either time-point. Cindunistat did not improve joint pain or function, but was generally well tolerated.

Conclusions Cindunistat (50 or 200 mg/day) did not slow the rate of JSN versus placebo. After 48-weeks, KLG2 patients showed less JSN; however, the improvement was not sustained at 96-weeks. iNOS inhibition did not slow OA progression in KLG3 patients.

Clinical trial listing NCT00565812