A Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics of a Single Dose of Cenerimod

Healthy Clinical Trial

Official title:

An Open-label, Parallel-group Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cenerimod After Single-dose Administration in Subjects With Hepatic Impairment and in Healthy Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04819464
• Other study ID #: ID-064-106
• Secondary ID: 2020-006002-23
• Status: Recruiting
• Phase: Phase 1
• Start date: August 19, 2021
• Est. completion date: March 29, 2024

Study information

• Verified date: November 2023
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: Idorsia Clinical Trial Information USA
• Phone: + 1 856 66 13 721
• Email: idorsiaclinicaltrials[@]idorsia.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, open-label, single-dose, phase 1 study, to assess the effect of mild and moderate hepatic impairment on the pharmacokinetics of cenerimod (ACT-334441).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: March 29, 2024
• Est. primary completion date: March 29, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• Signed informed consent in a language understandable to the participant prior to any study-mandated procedure.

• Women of child bearing potential must have a negative serum pregnancy test at screening, a negative urine pregnancy test on Day -1, and must agree to consistently and correctly use a highly effective method of contraception (i.e., failure rate of less than 1%).

• Women of non-childbearing potential must have a medical history of previous bilateral salpingectomy, salpingo-oophorectomy or hysterectomy, premature ovarian failure confirmed by a specialist gynecologist; or, be post-menopausal, defined as 12 consecutive months with amenorrhea prior to screening without alternative medical cause and confirmed with a follicle-stimulating hormone test.

• Body mass index of 18.0 to 32.0 kg/m2 (inclusive) at screening.

• Negative SARS-CoV-2-testing prior to Day -1 or documented vaccination against COVID-19 at least 3 months prior screening.

• Ability to communicate well with the investigator, in a language understandable to the participant, and to understand and comply with the requirements of the study.

Exclusion Criteria:

General (Group A, B and C)

• Pregnant or lactating women.

• Participation in a clinical study involving study treatment administration within 30 days prior to screening or in more than 2 clinical studies within 1 year prior to screening.

• Previous exposure to cenerimod.

• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, elimination (ADME) of the study treatment except for those related to liver cirrhosis or appendectomy and herniotomy.

• International Normalized Ratio greater than 2 at screening.

• Encephalopathy grade greater than or equal to 1.

• Clinically relevant abnormalities on a 12-lead ECG, recorded after 5 minutes in the supine position at screening and on Day 1 pre-dose.

• Presence of herpes simplex, disseminated zoster, or other opportunistic infections.

• Vaccination with live or live attenuated vaccines in the previous 4 weeks.

• Previous treatment with antiarrhythmic medications of class Ia or III 2 weeks or 5 half-lives, whichever is longer, prior to study treatment administration.

• Active retinopathy or macular edema at screening.

• Severe chronic obstructive pulmonary disease at screening.

• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

• Legal incapacity or limited legal capacity at screening.

Additional inclusion criteria for participants with hepatic impairment (Group A and B)

• Clinically relevant findings in clinical laboratory tests (hematology, coagulation, clinical chemistry, and urinalysis) at screening and on Day -1, except for those related to liver cirrhosis.

Additional exclusion criteria for healthy subjects (Group C)

• Clinically relevant findings in clinical laboratory tests (hematology, coagulation, clinical chemistry, and urinalysis) at screening and on Day -1.

• Previous treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines such as St. John's Wort, homeopathic preparations, vitamins, and minerals) within 2 weeks or 5 t½ prior to study treatment administration, whichever is longer (excluding contraceptives and HRT).

• Aspartate aminotransferase and alanine aminotransferase above the upper limit of normal.

Related Conditions & MeSH terms

• Healthy
• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Cenerimod
A single oral dose of 0.5 mg.

Locations

Country	Name	City	State
Hungary	CRU Hungary	Kistarcsa
Portugal	BlueClinical Phase 1 Hospital de Prelado	Porto

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Countries where clinical trial is conducted

Hungary,  Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curves (AUC0-t): cenerimod		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Primary	Area under the plasma concentration-time curve from zero to infinity (AUC0-inf): cenerimod		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Primary	Maximum plasma concentration (Cmax): cenerimod.		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Primary	Time to reach Cmax (tmax): cenerimod		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Primary	Terminal half-life (t½): cenerimod		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Primary	Plasma protein binding of cenerimod		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Primary	Apparent clearance (CL/F) of cenerimod		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Primary	Apparent volume of distribution (Vz/F) of cenerimod		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Secondary	Total lymphocyte count		Multiple sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Secondary	Change from baseline at each time point of measurement in electrocardiogram QT interval		Pre-defined times on Day 1 (pre-dose) up to Day 105.
Secondary	Change from baseline in body weight		Day -1 and Day 105.
Secondary	Change from baseline in systolic and diastolic blood pressure (in the supine position)		Predefined times on Day 1 (pre-dose) up to Day 105.
Secondary	Incidence of abnormal laboratory test results		Multiple sampling at predefined times on Day 1 (pre-dose) up to Day 105.
Secondary	Adverse events and serious adverse events		Day 1 up to Day 105.