Cindunistat hydrochloride maleate (SD-6010) is an orally-administered, selective, time-dependent and irreversible inhibitor of human iNOS (hiNOS). In vivo studies using the canine anterior cruciate ligament-transection model have demonstrated that cindunistat improves synovial fluid nitrite and nitrotyrosine biomarkers, osteophyte formation and cartilage lesions. Cindunistat has also been shown to improve pain behaviour in rodent models of inflammatory and neuropathic pain. Based on its potential to inhibit NO production and an early clinical development programme, the disease-modifying efficacy and safety profile of cindunistat was studied in a 2-year proof-of-concept clinical trial of patients with knee OA. Cindunistat (50 or 200 mg/day) did not slow the rate of joint space narrowing versus placebo. After 48-weeks, KLG2 patients showed less joint space narrowing; however, the improvement was not sustained at 96-weeks. iNOS inhibition did not slow OA progression in KLG3 patients.