Cold pressure test
Each subject performed CPT at screening, day -1, and day 10 of each
treatment period, approximately 3.5 hours after the start of a moderate
breakfast. CPT was conducted approximately at the same time of the day,
to reduce the impact of circadian variations of BP on the study
outcomes. BP and haemodynamic variables were collected during the CPT
using the Finapres® NOVA monitor (Finapres Medical Systems, Amsterdam).
The CPT procedure was conducted using the Advanced Hemodynamics software
application (Finapres Medical Systems, Amsterdam) to allow for the
characterisation of further haemodynamic parameters. The following
parameters were collected: SBP, DBP, HR, mean arterial pressure (MAP),
cardiac output (CO), cardiac index (CIn), stroke volume (SV), SV index
(SVI), total peripheral resistance (TPR), cardiac contractility (dP/dt)
and left ventricular ejection time (LVET).
The test included three phases: i) rest phase (5 minutes), ii) cold
stimulus phase (3 minutes), and iii) recovery phase (5 minutes). During
the cold stimulus phase of CPT, subjects inserted their left hand up to
the wrist in a temperature-controlled (4±0.5 ºC) water bath, for three
minutes.
The pharmacodynamics analysis set (PD population) included all subjects
who received at least one dose of the IMP and had at least one valid
post-dose for the corresponding PD assessment. Those subjects who belong
to the PD set and did not deviate from the protocol in a way that might
affect the evaluation of the corresponding PD variable were included in
the per-protocol pharmacodynamics analysis set (PP-PD population).