Purpose <p>Trientine dihydrochloride <b>(</b>TETA-2HCl) – a copper-selective chelator that forms a stable soluble complex with copper (Cu) and promotes excretion of this complex via the urine – is used as a treatment in Wilson Disease (WD) patients who are intolerant to D-penicillamine. Although in clinical practice patients are instructed to take TETA-2HCl on an empty stomach at least one hour before meals or two hours after meals, the effect of food on the pharmacokinetics of TETA-2HCl has not previously been systematically investigated in humans.</p> Methods <p>In this open-label, single dose, randomized, two period cross-over study in healthy adults, a single oral dose of 600&#xa0;mg of TETA-2HCl (2 × 300&#xa0;mg capsules) was once administered under fed and once under fasted conditions with a wash-out period of at least one week. Blood samples were collected for up to 48&#xa0;h after each dosing for analysis of plasma trientine (TETA) and its metabolites N1-acetyltriethylenetetramine (MAT) and N1-N10-diacetyltriethylenetetramine (DAT).</p> Results <p>Food had a significant effect on the pharmacokinetics of TETA and its metabolites MAT and DAT. Maximum plasma concentrations, and the exposures of TETA are significantly reduced by food (C_max: 45%, AUC_0 − t and AUC_{0 − inf}: 44%.). Similar effects were seen for the metabolites MAT and DAT. The tolerability of treatment with TETA-2HCl was not affected by the intake of food.</p> Conclusion <p>The study shows a significant impact of food on the pharmacokinetics of TETA, supporting the current instruction on administration of TETA-2HCl on an empty stomach in clinical practice.</p> <p>ClinicalTrials.gov Identifier: EudraCT number: 2018-001982-17. Date registered: 16 May 2018.</p>