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)-..