A randomised, placebo controlled, comparative trial of the gastrointestinal safety and efficacy of AZD3582 versus naproxen in osteoarthritis

Abstract

Objective: To evaluate the gastrointestinal safety and efficacy of the COX inhibiting nitric oxide donator AZD3582 in patients with hip or knee osteoarthritis.

Methods: 970 patients were randomised (7:7:2) to AZD3582 750 mg twice daily, naproxen 500 mg twice daily, or placebo twice daily in a double blind study. The primary end point was the six week incidence of endoscopic gastroduodenal ulcers (diameter > or =3 mm). Overall damage measured on the Lanza scale was a secondary end point. Safety and tolerability assessments included endoscopic upper gastrointestinal erosions and the gastrointestinal symptom rating scale (GSRS). Efficacy was primarily assessed by WOMAC.

Results: The incidence of ulcers with AZD3582 was 9.7% and with naproxen 13.7% (p = 0.07, NS), v 0% on placebo. The incidence of Lanza scores >2 was higher with naproxen (43.7%) than with AZD3582 (32.2%) (p<0.001). Compared with baseline, significantly fewer ulcers and erosions developed in stomach and stomach/duodenum combined, and fewer erosions developed in stomach, duodenum, and both combined on AZD3582 than on naproxen. GSRS reflux and abdominal pain subscale scores were lower for AZD3582 than for naproxen but there was no difference for indigestion, constipation, and diarrhoea. AZD3582 was as effective as naproxen at improving WOMAC scores. Both agents were well tolerated, with no significant effects on blood pressure.

Conclusions: At doses with similar efficacy in relieving osteoarthritis symptoms, the primary end point of six week endoscopic gastroduodenal ulcer incidence was not significantly different between AZD3582 and naproxen. Most secondary endoscopic gastrointestinal end points favoured AZD3582.

Figure 1

Patient disposition in a six week placebo controlled trial of the gastrointestinal safety and efficacy of AZD3582 and naproxen in patients with osteoarthritis.

Figure 2

Incidence and location of ulcers ⩾3 mm or ⩾5 mm (with depth) in osteoarthritic patients treated with AZD3582 or naproxen.

Figure 3

Mean supine systolic blood pressure in patients with osteoarthritis receiving AZD3582, naproxen, or placebo. Error bars = SD.