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

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

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).

Study Overview

• Status: Completed
• Conditions: Healthy; Hepatic Impairment
• Intervention / Treatment: Drug: Cenerimod

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hungary
  • Kistarcsa, Hungary, H2143
    • CRU Hungary
• Portugal
  • Porto, Portugal, 4250-449
    • BlueClinical Phase 1 Hospital de Prelado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 exclusion 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Participants with mild hepatic impairment; Participants with mild hepatic impairment (Child-Pugh Score of 5 to 6).	Drug: Cenerimod; A single oral dose of 0.5 mg.; Other Names: ACT-334441
Experimental: Group B: Participants with moderate hepatic impairment; Participants with moderate hepatic impairment (Child-Pugh Score of 7 to 9).	Drug: Cenerimod; A single oral dose of 0.5 mg.; Other Names: ACT-334441
Experimental: Group C:Healthy participants; Healthy participants will be matched to the participants with hepatic impairment based on age and body weight.	Drug: Cenerimod; A single oral dose of 0.5 mg.; Other Names: ACT-334441

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.
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.
Maximum plasma concentration (Cmax): cenerimod.	Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Time to reach Cmax (tmax): cenerimod	Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Terminal half-life (t½): cenerimod	Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Plasma protein binding of cenerimod	Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Apparent clearance (CL/F) of cenerimod	Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Apparent volume of distribution (Vz/F) of cenerimod	Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.

Secondary Outcome Measures

Outcome Measure	Time Frame
Total lymphocyte count	Multiple sampling at predefined times on Day 1 (pre-dose) up to Day 98.
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.
Change from baseline in body weight	Day -1 and Day 105.
Change from baseline in systolic and diastolic blood pressure (in the supine position)	Predefined times on Day 1 (pre-dose) up to Day 105.
Incidence of abnormal laboratory test results	Multiple sampling at predefined times on Day 1 (pre-dose) up to Day 105.
Adverse events and serious adverse events	Day 1 up to Day 105.

Collaborators and Investigators

• Sponsor: Viatris Innovation GmbH
• Investigators: Study Director: Clinical Trials, Viatris Innovation GmbH

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2021
• Primary Completion (Actual): August 18, 2024
• Study Completion (Actual): August 18, 2024

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 29, 2021

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; cenerimod
• Other Study ID Numbers: ID-064-106; 2020-006002-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No