Cold pressure test
The arithmetic means of SBP, DBP, and HR in each of the three phases of CPT, at day -1 and day 10, following administration of zamicastat and placebo are presented in Table 1 . The CPT was effective in eliciting a BP and HR response. During the cold stimulus phase of the CPT, SBP, DBP, and HR increased significantly in relation to the rest phase, irrespective of study day (day -1 or day 10) and treatment (zamicastat or placebo) (Table 2 ).
In comparison to placebo, the difference between cold stimulus and rest phases at day 10 adjusted to baseline (day -1), following administration of zamicastat, showed an estimated decrease of -4.62 mmHg for SBP which attained statistical significance (p=0.020). For DBP and HR, the difference between zamicastat against placebo was -1.86 mmHg and 0.81 bpm respectively; however, they were not statistically significant (p>0.05) (Table 3 ).
Compared to placebo, the difference between cold stimulus and rest phases at day 10, adjusted to baseline (day -1) following administration of zamicastat showed a statistically significant decrease of -2.62 mmHg in MAP response to cold stimulus during CPT (p=0.025), but not for the other haemodynamic parameters assessed (Table 4 ). Maximum response achievable (Emax) and time to occurrence of Emax (TEmax) for SBP, DBP, and HR were similar between zamicastat and placebo treatments, and the area under the effect time curve (AUEC) was slightly decreased with zamicastat treatment when compared to placebo. However, there were no statistically significant differences between zamicastat and placebo in Emax, TEmax and AUEC derived for SBP, DBP, and HR, following 10 days of treatment.
At each CPT phase (rest, cold stimulus, and recovery), no differences between zamicastat and placebo adjusted to baseline were observed for SBP, DBP, HR, MAP and haemodynamic parameters (CO, CI, SV, SVI, TPR, dP/dT and LVET)-..