Study of Possible Effects of the Drugs Propylthiouracil, Riociguat and Perphenazine on Circulation of Healthy Volunteers
Status:
Recruiting
Trial end date:
2021-04-30
Target enrollment:
Participant gender:
Summary
This trial is part of the Horizon 2020 project, REPO-TRIAL, on in-silico, mechanism-based
drug repurposing in high unmet-medical-need indications. This project aims to identify
causal, rather than symptomatic disease mechanisms for highly precise and effective
interventions. Here a signalling module comprised of reactive oxygen species (ROS) formation
and cyclic GMP signalling has been identified to be involved in post-stroke
blood-brain-barrier disruption and neuronal death. It can be targeted by repurposing three
drugs, which inhibit overshooting nitric oxide (NO) and ROS formation, respectively, and
stimulate compromised neuroprotective cyclic GMP formation. It is possible that two of the
drugs (riociguat, perphenazine) may cause a drop and one drug an elevation of blood pressure
(propylthiouracil) leading to an overall drop in blood pressure. On top of that, the three
drugs may synergise on blood pressure in a previously not recognised manner. These potential
safety concerns, expressed in a scientific advice meeting by the Federal Institute for Drugs
and Medical Devices (BfArM), shall be tested in the present phase I safety trial.
The trial consists of a screening visit (SCR), a treatment period, and an EOT visit. In the
treatment period, after a baseline evaluation, single doses of all three substances will be
administered concurrently. Provocation manoeuvres (tilt table) will be performed with the
goal of generating maximum safety information on drug-induced blood pressure changes.
Concurrently, a 24-h electrocardiogram (ECG) will be recorded (Holter ECG) and blood samples
will be drawn for exploratory biomarker analyses, quantification of riociguat, and optional
pharmacokinetic analyses of perphenazine and propylthiouracil.