We investigated potential drug-drug interactions between vandetanib and metformin [ organic cation transporter 2 ( OCT2 ) substrate ; NCT01551615 ] ; digoxin [ P-glycoprotein ( P-gp ) substrate ; NCT01561781 ] ; midazolam [ cytochrome P450 ( CYP ) 3A4 substrate ; NCT01544140 ] ; omeprazole ( proton pump inhibitor ) or ranitidine ( histamine H2-receptor antagonist ; both NCT01539655 ) .