Status:
COMPLETED
Possible Effects of Propylthiouracil, Riociguat and Perphenazine on Circulation of Healthy Volunteers
Lead Sponsor:
Maastricht University
Collaborating Sponsors:
European Commission
Conditions:
Drug Drug Interaction
Safety Issues
Eligibility:
All Genders
18-64 years
Phase:
PHASE1
Brief 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 sym...
Detailed Description
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 sym...
Eligibility Criteria
Inclusion
- Age 18-64 years (y) inclusive at the time of consent,
- Males and females of child-bearing potential who are willing to use a highly effective method of contraception during the treatment and for 1 week after the administration of the IMP or women not of child-bearing potential (WNCBP) or individuals who are convincingly sexually abstinent.
- Understanding, ability, and willingness to fully comply with trial interventions and restrictions, and
- Ability to provide written, personally signed, and dated informed consent to participate in the trial, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6, and applicable regulations, prior to any trial-related interventions.
- Healthy volunteers defined as absence of:
- Clinically significant or relevant abnormalities in the medical history, physical examination (e.g. heart murmur), and laboratory evaluation as assessed by the investigator,
- Medical disorder that may make the participant unlikely to fully complete the trial, or any condition that presents undue risk from the IMP or trial interventions,
- Clinically relevant ongoing or clinically relevant history of physical or psychiatric illness as judged by the investigator,
- Blood pressure \< 110 mmHg systolic or \< 65 mmHg diastolic, or known orthostatic dysregulation
- History of syncope
- Resting heart rate \< 50bpm or \> 90 bpm
- QTc prolongation (\> 460 ms)
- Bleeding disorders
- Acute or chronic illness or clinically relevant finding known or expected to modify absorption, distribution, metabolism, or excretion of prophylthiouracil, riociguat, or perphenazine,
- History of hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption
- Clinically relevant findings in any of the following investigations at SCR. (Minor deviations of laboratory values from the normal range can be acceptable, if judged by the investigator to be of no clinical relevance for this trial.), i. Haemoglobin (Hb) \< 12 g/dl (males) or \< 11 g/dl (females), ii. Creatinine (Crea) clearance (Cl) \< 60 ml/min (Cockcroft-Gault), iii. Bilirubin \> upper limit of normal (ULN) x 1.2; In case of suspected Gilbert's disease: non-fasting total bilirubin ≤ ULN x 1.2 and fasting total bilirubin ≤ ULN x 1.5 are acceptable, iv. Alanine aminotransferase (ALT) \> ULN x 1.1, v. Aspartate aminotransferase (AST) \> ULN x 1.2, vi. Creatine kinase (CK) not within normal limits (volunteers with CK elevations between ULN and ULN x 3 may be included if troponin T is negative), and vii. Thyroid-stimulating hormone (TSH) not within normal limits.
- Regular medication except for hormonal contraception, iodide, and levothyroxine
Exclusion
- Any known history of severe allergic or anaphylactic reactions to drugs or food or any other clinically significant allergies (except mild forms of hay fever),
- Any known allergies to compounds or additives of prophylthiouracil, riociguat, or perphenazine,
- A positive human immunodeficiency virus (HIV) or hepatitis C antibody screen,
- A positive result in the drug screening test at SCR,
- Any intake of substances known to induce or inhibit prophylthiouracil, riociguat, or perphenazine metabolizing enzymes or transporters within a period of \< 5 times the respective elimination half-lives (t1/2) or 2 weeks (whatever is longer) with regard to the expected date of first dose of IMP,
- Intake of medication with impact on platelet function (e.g. NSAID) within two weeks prior to the first biomarker blood sample,
- Relevant consumption of grapefruit or products thereof within 7 d prior to the expected date of first dose of IMP and expected noncompliance to refrain from such products until 48 h after exposure,
- Smoking within 24 h prior to visit 1 and/or 48 h post IMP administration, caffeine consumption on treatment day, and expected noncompliance to refrain from these products
- Expected nonadherence to refrain from alcohol 24 h prior to visit 1 until 48 h after exposure, or pathologic alcohol consumption
- Use of an IMP within 30 d prior to the expected date of receiving the first dose of IMP or active enrolment in another drug or vaccine clinical trial.
- Specific contraindications to propylthiouracil
- \- History of agranulocytosis, vasculitis, or liver cell damage
- Specific contraindications to riociguat (not covered above)
- Use of phosphodiesterase 5 (PDE5) inhibitors
- Severe liver damage
- Pregnancy
- Use of nitrates or NO donors
- Specific contraindication to perphenazine:
- Hypersensitivity to perphenazine, other drugs of this substance class, or any of its excipients
- Acute intoxication with central depressant drugs (e.g. opiates, hypnotics, antidepressants, antiepileptics, neuroleptics, tranquilizers), or alcohol
- Severe damage of blood cells or of bone marrow
- Severe liver disease
- Severe depression
- Comatose state
Key Trial Info
Start Date :
March 18 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
February 28 2022
Estimated Enrollment :
8 Patients enrolled
Trial Details
Trial ID
NCT04776499
Start Date
March 18 2021
End Date
February 28 2022
Last Update
April 4 2022
Active Locations (1)
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1
UniversitätsKlinikum Heidelberg - Medizinische Klinik
Heidelberg, Germany, 69120