Safety, tolerability and pharmacokinetics of CHF 6001, a novel selective inhaled PDE4 inhibitor, in healthy volunteers

BACKGROUND: CHF 6001 is under development for the treatment of chronic obstructive pulmonary disease (COPD) and asthma. Good safety and tolerability of CHF 6001 was demonstrated up to 2000µg doses in healthy volunteers (HV) (1) . The aim of this study was to assess safety and tolerability of higher doses. METHODS: Three doses (2400, 4000 and 4800µg) of CHF 6001 were administered using NEXThaler ® , a proprietary multidose reservoir dry powder inhaler (DPI) to one cohort of 12 HV (9 active: 3 placebo) according to a randomized, double-blind, single-dose, placebo-controlled ascending design and to three cohorts of 12 HV each (9 active: 3 placebo), as a 2-week twice-daily, sequential dose escalation, parallel-group design. RESULTS: CHF 6001 was well tolerated. No serious adverse events (AEs) were reported. Limited gastrointestinal (GI) AEs were reported: diarrhoea (n=1), abdominal pain (n=1), flatulence (n=1) and oral pain (n=1) out of 27 HV on CHF 6001 versus none out of 9 HV on placebo. CHF 6001 showed dose proportional systemic exposure (C max and AUC). Mean half-life (t 1/2 ) ranged from 40 to 49 h, the steady state was reached within 8 days of treatment with 6 fold higher exposure compared to the first administration. CONCLUSIONS: CHF 6001 was safe and tolerated at daily doses up to 4800µg for 14 days in HV. No significant GI intolerance was observed. CHF 6001 showed linear pharmacokinetics in the tested dose range. (1) O. Esposito et al. – ERS 2013 Poster Presentation.