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 a sthma. The current phase II study was designed as a multicentered, dou ble blinded, randomized, placebo-controlled, parallel-group pilot stud y to investigate the efficacy of the B-2 BK receptor antagonist Icatib ant 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, Treat ment 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 ob jective pulmonary function tests (PFTs) measured by the investigators (e.g. FEV(1) and PEFR). At 3 mg t.i.d., a statistically significant di fference (p < 0.001) between Icatibant and placebo of about 10% was ac hieved after if weeks of treatment for all PFTs. At 900 mu g t.i.d., t he improvement in PFTs was smaller, By contrast, no clinically relevan t improvement in global symptom score (nor a reduction of rescue medic ation) was found when compared with placebo. The observed improvement in objective PFTs started between weeks one and two, gradually increas ed until the end of active treatment, and slowly decreased during the placebo run-out phase, suggesting an anti-inflammatory effect. No acut e bronchodilator effect was found. In conclusion, Icatibant showed a p rofile expected for an anti-inflammatory asthma drug.