Plasma Catecholamines
At day 10, zamicastat elicited a significant increase of 12.63 ng/L (p=0.040) and 19.22 ng/L (p=0.001) in plasma DA before CPT and after CPT. For day -1 and 10, following treatment with zamicastat and placebo, no differences were observed for DA, EPI, and NE plasma concentrations, when adjusted to baseline plasma concentrations, after CPT and before CPT. After CPT, a significant difference between zamicastat and placebo of 15.93 ng/L was observed (p=0.040) on the change from baseline EPI plasma concentration. For DA and NE change from baseline plasma concentrations, no statistically significant differences (p>0.05) were observed (Table 5 ).
Twenty-four-hour urinary excretion profile of catecholamines and catecholamine metabolites The observed 24-hour urinary excretion of DA, EPI, and NE was generally lower with zamicastat than with placebo from day 3 to day 10 (n=21). At day 10, zamicastat was shown to have a statistically significant decrease in EPI (-3.96 μg/24h, p=0.007) and NE (-7.54 μg/24h, p=0.017) on the change from baseline 24-hour urine excretion profile when compared to placebo. No difference was observed for DA 24-hour urinary excretion profile, following 10 days of treatment (Figure 2 ). Compared to placebo, zamicastat was associated to an increase in HVA urinary excretion of 1.75 mg/24 h (p<0.001) and a decrease in VMA urinary excretion of 1.97 mg/24 h (p<0.001), which was observed from baseline up to day 10 (Figure 2 ). No differences were observed for normetanephrine or metanephrine.