Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of sonidegib in healthy volunteers

AimsThis study aimed to evaluate the impact of esomeprazole on the pharmacokinetics of sonidegib. MethodsThis Phase I study evaluated the impact of the proton pump inhibitor (PPI) esomeprazole on the oral absorption and pharmacokinetics (PKs) of a single dose of sonidegib under fasted conditions. A total of 42 healthy subjects were enrolled to receive either sonidegib alone (200mg single dose) or sonidegib in combination with esomeprazole (40mg pre-treatment 5days and combination were given on day 6). Primary PK parameters assessed in the study were area under the concentration-time curve (AUC) from 0-14days and 0-7days and maximum observed plasma concentration (C-max). ResultsThe plasma exposure (AUC0-14d, AUC0-7d and C-max) of a single 200mg oral dose of sonidegib was decreased by 32-38% when sonidegib was co-administered with esomeprazole compared with sonidegib alone, with no apparent change in elimination slope and t(max). Baseline gastric pH was similar between the two arms. ConclusionsThese results suggest a modest reduction in the extent of sonidegib absorption by esomeprazole. There was no obvious metabolic drug-drug interaction between the two agents. Both sonidegib and esomeprazole were well tolerated in the study population.