Healthy, Hepatic Impairment
Conditions
Brief 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).
Interventions
DRUGCenerimod
A single oral dose of 0.5 mg.
Sponsors
Viatris Innovation GmbH
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
The 3 groups will be sequentially studied. Dosing will start in the participants with mild hepatic impairment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Apparent clearance (CL/F) of cenerimod | Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98. |
| 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 volume of distribution (Vz/F) of cenerimod | Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98. |
Secondary
| Measure | Time frame |
|---|---|
| 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. |
| Total lymphocyte count | Multiple sampling at predefined times on Day 1 (pre-dose) up to Day 98. |
Countries
Hungary, Portugal
Outcome results
None listed