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The Effect of Severe Kidney Impairment on Cenerimod Pharmacokinetics

Phase 1
Completed
Conditions
Healthy
Renal Impairment
Interventions
Registration Number
NCT05004311
Lead Sponsor
Idorsia Pharmaceuticals Ltd.
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group B (healthy)CenerimodEight (8) control participants, matched to the 8 severe renal impaired participants enrolled in Group A.
Group A (severe renal function impairment)CenerimodEight (8) participants with severe renal impairment.
Primary Outcome Measures
NameTimeMethod
The time to reach Cmax (tmax) of cenerimodTotal duration: up to 52 days
Extent of cenerimod protein plasma binding (PPB)Total duration: up to 52 days
The maximum plasma concentration (Cmax) of cenerimodTotal duration: up to 52 days
Area under the plasma concentration-time curve (AUC from 0 to infinity) of cenerimodTotal duration: up to 52 days
Apparent volume of distribution (Vz/F) of cenerimodTotal duration: up to 52 days
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 cenerimodTotal duration: up to 52 days
Terminal half-life (t½) of cenerimodTotal duration: up to 52 days
Apparent oral clearance (CL/F) of cenerimodTotal duration: up to 52 days
Secondary Outcome Measures
NameTimeMethod
Change from baseline at each time point of measurement in electrocardiogram QT intervalTotal duration: up to 66 days
Change from baseline in body weightTotal duration: up to 66 days
Incidence of abnormal laboratory test resultsTotal duration: up to 66 days
Change from baseline in systolic and diastolic blood pressure (in the supine position)Total duration: up to 66 days
Total lymphocyte count count.Total duration: up to 66 days

Trial Locations

Locations (1)

BlueClinical Phase 1 Hospital de Prelado

🇵🇹

Porto, Portugal

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