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A Study to Evaluate Pharmacokinetic Parameters of Eliglustat in Healthy Volunteers Who Are CYP2D6 Extensive or Poor Metabolizers

Phase 1
Completed
Conditions
Gaucher's Disease
Interventions
Registration Number
NCT06188325
Lead Sponsor
Sanofi
Brief Summary

The primary objective of the study is to evaluate dose proportionality and pharmacokinetics for three different dose levels of eliglustat after single and repeated administration.

Detailed Description

Duration of the study for each subject will be between 42 to 79 days, including a screening period up to 28 days, 3 treatment periods of 7 days each period, a washup period of 7-10 days, and an end-of-study visit 8+/-2 days after the last administration.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
18
Inclusion Criteria
  • Body weight between 50.0 and 100.0 kg, inclusive, if male, and between 40.0 and 90.0 kg, inclusive, if female, body mass index between 18.0 and 30.0 kg/m2, inclusive.
  • Certified as healthy by a comprehensive clinical assessment (detailed medical history, complete physical examination, laboratory parameters, electrocardiograms (ECG)).
  • Having given written informed consent prior to undertaking any study-related procedure
  • Having given written informed consent prior to undertaking any study-related procedure
Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

  • Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness.

The following classes of drugs administered within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, with the exception of hormonal contraception or menopausal hormone replacement therapy:

  • Drugs that are strong inducers of CYP3A (eg, rifampin, carbamazepine, phenobarbital,phenytoin, St. John's Wort).
  • Drugs that inhibit CYP2D6 or CYP3A (eg, paroxetine, ketoconazole, fluconazole,ranitidine).
  • Drugs that are substrates for P-gp (phenytoin, colchicine and dabigatran etexilate) or CYP2D6 (metoprolol, tricyclic antidepressants such as nortriptyline, amitriptyline, or imipramine, and phenothiazines such as perphenazine and chloropromazine).

The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Group 1EliglustatCYP2D6 Extensive metabolizers - dose 1, 2 and 3 of eliglustat
Group 2EliglustatCYP2D6 Poor metabolizers - dose 1, 2 and 3 of eliglustat
Primary Outcome Measures
NameTimeMethod
Pharmacokinetic (PK) parameter: CmaxMultiple timepoints up to Day 35

Eliglustat after single and repeated doses: Maximum plasma concentration observed (Cmax)

Pharmacokinetic (PK) parameter: AUCMultiple timepoints up to Day 35

Eliglustat after single and repeated doses: Area under the plasma concentration versus time curve (AUC)

Pharmacokinetic (PK) parameter: tmaxMultiple timepoints up to Day 35

Eliglustat after single and repeated doses: Time to reach Cmax

Pharmacokinetic (PK) parameter: AUC0-TMultiple timepoints up to Day 35

Eliglustat after single and repeated doses: Area under the plasma concentration versus time curve calculated using the trapezoidal method (AUC0-T)

Secondary Outcome Measures
NameTimeMethod
Pharmacokinetic (PK) parameter: t1/2zMultiple timepoints up to Day 35

Eliglustat after single and repeated doses: Terminal half-life associated with the terminal slope (λz)

Pharmacokinetic (PK) parameter: CtroughMultiple timepoints up to Day 35

Eliglustat after single and repeated doses: Plasma concentration observed just before treatment administration during repeated dosing

Pharmacokinetic (PK) parameter: AUClastMultiple timepoints up to Day 35

Eliglustat after single and repeated doses: Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast

Pharmacokinetic (PK) parameter: tlastMultiple timepoints up to Day 35

Eliglustat after single and repeated doses: Time corresponding to the last concentration above the limit of quantification, Clast

Pharmacokinetic (PK) parameter: CL/FMultiple timepoints up to Day 35

Eliglustat after single and repeated doses: Eliglustat after repeated dose: CL/F

Number of participants with treatment emergent adverse events, serious adverse events, and adverse event of special interestUp to Day 42

Safety was assessed using clinical laboratory evaluations, ECG parameters, and adverse events spontaneously reported by the subject or observed by the Investigator

Trial Locations

Locations (1)

M.D.Covance Clinical Research Unit 1341 W

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Dallas, Texas, United States

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