Efficacy and tolerability of Icatibant (Hoe 140) in patients with moderately severe chronic bronchial asthma

Bradykinin (BK) has been identified as a mediator in human bronchial asthma. The current phase II study was designed as a multicentered, double blinded, randomized, placebo-controlled, parallel-group pilot study to investigate the efficacy of the B-2 BK receptor antagonist Icatibant in adult patients with chronic asthma. Patients were treated t.i.d. with 900 mu g or 3000 mu g of nebulized Icatibant, or placebo, Treatment was for I weeks, followed by a 2-week placebo run-out, Icatibant was very well tolerated, and led to a dose-dependent improvement in objective pulmonary function tests (PFTs) measured by the investigators (e.g. FEV(1) and PEFR). At 3 mg t.i.d., a statistically significant difference (p < 0.001) between Icatibant and placebo of about 10% was achieved after if weeks of treatment for all PFTs. At 900 mu g t.i.d., the improvement in PFTs was smaller, By contrast, no clinically relevant improvement in global symptom score (nor a reduction of rescue medication) was found when compared with placebo. The observed improvement in objective PFTs started between weeks one and two, gradually increased until the end of active treatment, and slowly decreased during the placebo run-out phase, suggesting an anti-inflammatory effect. No acute bronchodilator effect was found. In conclusion, Icatibant showed a profile expected for an anti-inflammatory asthma drug.