The effect of the inhaled PDE4 inhibitor CHF6001 on allergen-induced inflammation in asthmatics

The anti-inflammatory effect of CHF6001, a novel phosphodiesterase-4 (PDE4) inhibitor delivered via a dry powder inhaler, was evaluated in asthmatics on the airway response to allergen challenge (AC). METHODS: Thirty-six steroid-naive asthmatics with dual response to AC were enrolled in a randomized, double-blind, placebo-controlled, 3-way crossover trial. They received daily treatment with CHF6001 low dose (400 µg), high dose (1200 µg) or placebo for 9 days. On Day 9 subjects underwent AC and pharmacokinetic evaluation. RESULTS: Both doses of CHF6001 significantly attenuated the late asthmatic response (LAR): the weighted FEV1 AUC4-10h was reduced by 20% (p=0.014) and 30% (p<0.01) respectively with low and high dose compared with placebo. The maximum FEV1 fall during LAR was reduced by 16% (p=0.027) and 24% (p<0.01) with low and high dose, respectively. There was no effect on the early asthmatic response (0-2h post AC). Exposure to CHF6001 increased dose proportionally with peak plasma levels at 2 h post-dose and elimination half-lives of approximately 24 h. Systemic exposure to metabolites was low compared to the parent compound, suggesting limited formation in vivo . There were no gastrointestinal adverse events, except dyspepsia in one patient after both CHF6001 400 µg and placebo. CONCLUSIONS: CHF6001, a novel PDE4 inhibitor, optimized for inhaled delivery to improve efficacy and tolerability, significantly reduces LAR after allergen challenge. Both doses of CHF6001 were safe and well tolerated, particularly with respect to gastrointestinal side effects.