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

Viatris Innovation GmbH

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment; Healthy

Treatments: Drug: Cenerimod

Study type: Interventional

Funder types: Industry

Identifiers

NCT04819464

2020-006002-23 (EudraCT Number)

ID-064-106

Details and patient eligibility

About

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).

Enrollment: 24 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Group A: Participants with mild hepatic impairment

Experimental group

Description:

Participants with mild hepatic impairment (Child-Pugh Score of 5 to 6).

Treatment:

Drug: Cenerimod

Group B: Participants with moderate hepatic impairment

Experimental group

Description:

Participants with moderate hepatic impairment (Child-Pugh Score of 7 to 9).

Treatment:

Drug: Cenerimod

Group C:Healthy participants

Experimental group

Description:

Healthy participants will be matched to the participants with hepatic impairment based on age and body weight.

Treatment:

Drug: Cenerimod