ABSTRACT
INTRODUCTION: The clonidine mucoadhesive buccal tablet (MBT) is a novel delivery system resulting in high and sustained concentrations of clonidine in the oral cavity. In a phase II clinical trial, clonidine MBT reduced the incidence of severe oral mucositis (OM) compared to placebo in head and neck cancer patients undergoing chemoradiation. This study compared the pharmacokinetics (PK), safety and tolerability of clonidine MBT with a reference oral tablet (OT). METHODS: This was a randomised, three-period, single-dose crossover study in 36 healthy subjects aged 18-50 years. Eligibility was assessed within 14 days of the first dose. IMP was administered in the fasted state on day 1 of each treatment period. PK samples were collected up to 24 h (saliva)/96 h (blood) for measurement of the clonidine concentration. Safety and tolerability were evaluated at specified times throughout the study. A washout period of at least 7 days was observed between administrations. RESULTS: Clonidine MBT (50 and 100 µg) applied to the upper gum resulted in a dose-proportional increase in saliva (C max and AUC0-t ) and plasma (Cmax and AUC0-inf) clonidine levels. Clonidine MBT was considered to mimic a continuous release of clonidine in plasma, significantly decreasing the C max and AUC and increasing the T max when compared with the reference clonidine HCl tablets. Clonidine MBT exhibited high and prolonged concentrations in saliva where concentrations with the clonidine HCl tablet were negligible. Clonidine MBT exhibited a favourable safety profile with significantly fewer subjects reporting AEs (dry mouth and fatigue) and a reduction in blood pressure when compared to the reference clonidine HCl tablets. CONCLUSION: Clonidine MBT is well tolerated and exhibits proportional saliva and plasma PK over the 50-100-µg dose level. The MBT results in higher saliva concentrations and lower systemic exposure than OT, which was associated with a trend towards fewer adverse events and less dry mouth, fatigue and hypotensive effect. FUNDING: Onxeo SA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02548806.
