141 An open label investigation of the tolerability and pharmacokinetics of oral cysteamine in adults with cystic fibrosis

Abstract

Pre-clinical data obtained thus far suggests a role for cysteamine in CF. Cysteamine is a potent mucolytic, disrupts biofilms, is antimicrobial, and synergises with antibiotics. This study is the first to ascertain if oral cysteamine is absorbed in adult CF patients and enters bronchial secretions. Secondary aims were to explore tolerability and clinical outcomes. Patients aged ≥ 18 years with stable CF lung disease were started on oral cysteamine 450 mg od, this was increased weekly to 450 mg bd, 450 mg tds and 450 mg qds, subjects took 450 mg qds for 2 weeks. Patients were assessed weekly. To date 8 patients have been enrolled. When compared with cystinosis (for which oral cysteamine is already licensed), plasma half-life 240 min (SD 96) and volume of distribution 457 L (97) are increased in CF, but clearance 1.48 L/min (0.54), and maximal concentration 2.82 mg/L (1.91) are similar in CF. Cysteamine therapy was associated with a 0.8 (95% CI –1.6,3.2) log reduction in sputum microbial load (p = 0.4) and a 516% (110,922) reduction in sputum viscosity (p = 0.062). Weight declined by 0.75 kg (–0.42,1.93) (p = 0.166). Lung function did not change. Cysteamine therapy was associated with significant declines in CFQ-R domains of physical, vitality and treatment burden and improvement in role and health perception. This small study demonstrates that in stable patients with CF, oral cysteamine is absorbed and over 5 weeks is associated with promising improvements in sputum microbial load and viscosity. Trends in weight loss and quality of life are of concern. Oral cysteamine is a promising candidate adjunct for acute exacerbations of CF lung disease, long term oral use appears to be less promising.