MedTrace Logo

Possible Effects of Propylthiouracil, Riociguat and Perphenazine on Circulation of Healthy Volunteers

NCT04776499 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 8

Last updated 2022-04-04

No results posted yet for this study

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.

Conditions

  • Drug Drug Interaction
  • Safety Issues

Interventions

DRUG

Propylthiouracil, Riociguat, Perphenazine

Administration of propylthiouracil, riociguat, and perphenazine in combination Investigational medicinal product (IMP): Propylthiouracil: 100 mg, Riociguat: 1 mg, Perphenazine: 16 mg

Sponsors & Collaborators

Principal Investigators

  • Walter E. Haefeli, Prof. Dr. · University Hospital Heidelberg

Study Design

Allocation
NA
Purpose
OTHER
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
64 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2021-03-18
Primary Completion
2022-02-28
Completion
2022-02-28

Countries

  • Germany

Study Locations

More Related Trials

Entities

Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04776499 on ClinicalTrials.gov