Long-term safety and efficacy of zafirlukast in the treatment of asthma: Interim results of an open-label-extension trial

Purpose: To evaluate long-term safety and efficacy of oral zafirlukast (Z; 20 mg BID) during first 39 wks of ongoing non-randomized, multicenter, open-label extension (OLE) of a 13-wk, randomized (2:1), double-blind, placebo(P)-controlled trial in mild-to-moderate asthmatic patients maintained on β₂-agonist therapy. Methods: Patients (aged 12-76 yrs; FEV₁≥55% predicted) could elect to enter OLE after completing double-blind trial. Safety was evaluated by adverse events (AEs), laboratory tests, and physical and electrocardiographic examinations. Efficacy was assessed by spirometry measurements (FEV₁, FEV₁ % predicted, personal-best FEV₁) and treatment failure rates. Compliance was calculated as a percentage of treatment dispensed. After a visit at OLE wk 3 (wk 16), patients had visits every 12 wks. Results: A total of 443 patients (N_Z→_Z=310, N_P→_Z=133) entered OLE trial. Results through OLE wk 39 (wk 52) showed that 276 (62.3%) patients reported AEs and 17 (3.8%) withdrew for an AE or intercurrent illness; these results are consistent with those reported for double-blind trial [Fish JE et al. Clin Ther 1997;19:675-690]. Review by quarters showed occurrence of AEs in Z-treated groups (Q2-4) was similar to that in P group (Q1). Compared with baseline (wk 0), significant improvements (p≤0.02) in all spirometry measurements were noted in Z→Z and P→Z groups at OLE wk 3, with consistent and sustained effects noted at every OLE time point. Treatment failure rates ranged from 6.1% (Q2) to 3.0% (Q4) and were comparable with rates of worsening asthma reported by Fish et al. Mean compliance ranged from 98% (OLE wk 3) to 95% (OLE wk 39). Conclusions: Zafirlukast was well tolerated in asthmatic patients during 39-wk OLE period, with safety profile similar to that of placebo. Sustained efficacy and asthma control and good compliance were observed over extended treatment period. Clinical Implications: Results demonstrate long-term safety and effectiveness of anti-leukotriene agent.