For example, a second-generation ON drug candidate, Volanesorsen, targeting Apolipoprotein C-III, which has been tested in a phase I clinical study in healthy subjects, showed a non-linear (4.5 fold) increase in exposure when doubling the dose from 200 mg to 400 mg per week, resulting in severe thrombocytopenia in an undisclosed number of patients at 300 mg/wk (IONIS press release; [39]). The gene discussed is APOC3; the disease is Thrombocytopenia.