The Effect of Severe Kidney Impairment on Cenerimod Pharmacokinetics

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 Severe Renal Impairment and Control Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05004311
• Other study ID #: ID-064-107
• Secondary ID: 2021-001522-21
• Status: Completed
• Phase: Phase 1
• Start date: September 27, 2021
• Est. completion date: August 10, 2023

Study information

• Verified date: August 2023
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To investigate the PK of cenerimod in participants with severe renal impairment as compared to healthy control participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: August 10, 2023
• Est. primary completion date: July 27, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

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

• Women of childbearing potential must have a negative serum pregnancy test at screening, a negative urine pregnancy test on Day -1, and agree to consistently and correctly use a highly effective method of contraception.

• Women of non-childbearing potential.

• Body mass index of 18.0 to 35.0 kg/m2 (inclusive) at Screening

• Negative SARS-CoV-2 reverse transcription polymerase chain reaction test on Day -1.

Additional inclusion criteria for participants with severe renal impairment

• Estimated glomerular filtration rate (eGFR) at screening using the Modification of Diet in Renal Disease formula less-than 30 mL/min/1.73 m2 for participants with renal impairment. The eGFR value should be confirmed on Day -1.

• Systolic blood pressure (SBP) 100 to 180 mmHg, diastolic BP (DBP) 50 to 105 mmHg, and pulse rate 60 to 100 bpm (inclusive), on Day 1 pre-dose.

• Stable concomitant medications for at least 3 weeks prior to screening and up to Day 1.

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

• Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinanalysis) except for those related to renal impairment at Screening and on Day-1.

Additional inclusion criteria for control participants

• eGFR at Screening using the Modification of Diet in Renal Disease formula of = 90 mL/min/1.73 m2.

• SBP 90 to 139 mmHg, DBP 60 to 89 mmHg, and pulse rate 60 to 99 bpm, measured on the same arm, after 5 min in the supine position at screening and on Day 1 pre-dose.

Exclusion Criteria:

• Pregnant or lactating women.

• Participation in a clinical study involving study treatment administration within 3 months prior to screening or participation in more than 2 clinical studies within 1 year prior to Screening.

• Previous exposure to cenerimod.

• Known hypersensitivity to any excipients of the treatment formulation.

• Clinically relevant abnormalities on a 12-lead electrocardiogram at Screening and Day -1.

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

• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of the study treatment except for renal disease, appendectomy, herniotomy, or cholecystectomy.

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

• Legal incapacity or limited legal capacity at Screening.

Additional exclusion criteria for participants with severe renal impairment:

• Presence of severe cardiac disease.

• End-stage renal disease that requires dialysis.

• History of severe renal artery stenosis.

• Serum potassium concentration > 5.5 mmol/L.

• Presence of unstable diabetes mellitus.

• Strict fluid restriction.

• Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinalysis) except for those related to renal impairment at Screening and on Day -1.

Additional exclusion criteria for control participants

• Clinically relevant findings on the physical examination at Screening.

• Clinically relevant findings in clinical laboratory tests.

Related Conditions & MeSH terms

• Healthy
• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Cenerimod
A single oral dose of 0.5 mg cenerimod will be administered as a film-coated tablet in the morning of Day 1 under fasted conditions

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curve (AUC) from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t) of cenerimod		Total duration: up to 52 days
Primary	Area under the plasma concentration-time curve (AUC from 0 to infinity) of cenerimod		Total duration: up to 52 days
Primary	The maximum plasma concentration (Cmax) of cenerimod		Total duration: up to 52 days
Primary	The time to reach Cmax (tmax) of cenerimod		Total duration: up to 52 days
Primary	Terminal half-life (t½) of cenerimod		Total duration: up to 52 days
Primary	Apparent oral clearance (CL/F) of cenerimod		Total duration: up to 52 days
Primary	Extent of cenerimod protein plasma binding (PPB)		Total duration: up to 52 days
Primary	Apparent volume of distribution (Vz/F) of cenerimod		Total duration: up to 52 days
Secondary	Total lymphocyte count count.		Total duration: up to 66 days
Secondary	Change from baseline at each time point of measurement in electrocardiogram QT interval		Total duration: up to 66 days
Secondary	Change from baseline in body weight		Total duration: up to 66 days
Secondary	Change from baseline in systolic and diastolic blood pressure (in the supine position)		Total duration: up to 66 days
Secondary	Incidence of abnormal laboratory test results		Total duration: up to 66 days