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A Study to Assess the Effect of Erythromycin on the Test Medicine (SAR443820) When Given Orally as Tablets to Healthy Adult Male and Female Participants (Part A); and the Effect of Itraconazole on the Test Medicine (SAR443820) When Given Orally as Capsules to Healthy Adult Male Participants (Part B)

Phase 1
Completed
Conditions
Amyotrophic Lateral Sclerosis
Healthy Volunteer
Interventions
Registration Number
NCT05797753
Lead Sponsor
Sanofi
Brief Summary

This is a Phase 1, cross-over, 2-part study for pharmacokinetic (PK) assessment of SAR443820 when co-administered with cytochrome P450 3A4 (CYP3A4) inhibitors (erythromycin ethyl succinate (EES) in Part A and possibly itraconazole in Part B).

In Part A, the objective is to assess the effects of repeated administration of EES as CYP3A4 inhibitor, on the PK profile of a single oral dose of SAR443820 tablet in healthy male and female participants.

In Part B, the objective is to assess the effects of repeated administration of itraconazole on the PK profile of a single oral dose of SAR443820 capsule in healthy male participants.

Part A includes a screening period, Period 1 (SAR443820), a wash-out period and Period 2 (SAR443820 + EES). Part B includes a screening period, Period 1 (SAR443820), a wash-out period and Period 2 (SAR443820 + itraconazole). The washout period between single SAR443820 administration in Period 1 and the start of dosing with EES (Part A) or itraconazole (Part B) in Period 2 is at least 4 days.

The study duration is approximately 7 weeks for each Part A and Part B.

The treatment duration is:

* For SAR443820 (both Part A and Part B): 1 day in each Period; single dose of SAR443830 on Period 1 (P1)-Day 1 and on Period 2 (P2)-Day 6 for each Part.

* For EES (Part A): 9 days of treatment in Period 2 with P2-Day 1 starting at least 4 days after P1-Day 1.

* For itraconazole (Part B): the treatment duration lasts 11 days in Period 2 and it is fixed once the results of Part A are issued, P2-Day 1 starting at least 4 days after P1-Day 1.

Detailed Description

The study duration was approximately 7 weeks for each Part A and Part B.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
Inclusion Criteria
  • Part A: male or female participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent
  • Part B: male participant only must be 18 to 55 years of age inclusive, at the time of signing the informed consent
  • 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/m^2, inclusive
  • Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Exclusion Criteria
  • 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 - Any medication (including St John's Wort) 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; any non-live Covid-19 vaccine within the last 2 weeks before inclusion, any live attenuated vaccine within the last 28 days before inclusion and any other non-vaccine biological drugs given within 4 months before inclusion
  • Current enrollment in Part A (applicable for Part B) or past participation in previous clinical study on SAR443820
  • Positive result for hepatitis B, C or human immunodeficiency virus (HIV)
  • Positive result on urine drug screen
  • Positive urine alcohol test
  • Any consumption of citrus fruits (grapefruit, orange, etc) or their juices within 5 days before inclusion The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Part-A, Period-1SAR443820Single dose of SAR443820 tablet on Day 1
Part-A, Period-2SAR443820Single dose of SAR443820 tablet on Day 6, and erythromycin ethyl succinate (EES) three-time a day (TID) from Day 1 to Day 9
Part-B, Period-2ItraconazoleSingle dose of SAR443820 capsule on Day 6, and Itraconazole once daily (QD) from Day 1 to Day 11
Part-A, Period-2Erythromycin ethyl succinateSingle dose of SAR443820 tablet on Day 6, and erythromycin ethyl succinate (EES) three-time a day (TID) from Day 1 to Day 9
Part-B, Period-1SAR443820Single dose of SAR443820 capsule on Day 1
Part-B, Period-2SAR443820Single dose of SAR443820 capsule on Day 6, and Itraconazole once daily (QD) from Day 1 to Day 11
Primary Outcome Measures
NameTimeMethod
Part B: SAR443820: AUClastPeriod 1: Day 1 to Day 3; Period 2: Day 6 to Day 12
Part B: SAR443820: AUCPeriod 1: Day 1 to Day 3; Period 2: Day 6 to Day 12
Part A: SAR443820: Area under the plasma concentration from time zero to the last concentration above the limit of quantification (AUClast)Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10
Part A: SAR443820: Area under the plasma concentration (AUC)Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10
Secondary Outcome Measures
NameTimeMethod
Part A: SAR443820: Time to reach Cmax (tmax)Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10
Part A: SAR443820: Terminal half-life (t1/2z)Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10
Part B: SAR443820: CmaxPeriod 1: Day 1 to Day 3; Period 2: Day 6 to Day 12
Part B: SAR443820: tmaxPeriod 1: Day 1 to Day 3; Period 2: Day 6 to Day 12
Part B: SAR443820: t1/2zPeriod 1: Day 1 to Day 3; Period 2: Day 6 to Day 12
Part A: Erythromycin ethyl succinate concentrationsPeriod 2: Day 6 and Day 7
Part A: Erythromycin base concentrationPeriod 2: Day 6 and Day 7
Part B: Itraconazole: CmaxPeriod 2: Day 6 and Day 7
Part B: Itraconazole: AUClastPeriod 2: Day 6 and Day 7
Part B: Hydroxyitraconazole: CmaxPeriod 2: Day 6 and Day 7
Part B: Hydroxyitraconazole: AUClastPeriod 2: Day 6 and Day 7
Part A: number of participants with treatment emergent adverse events (TEAEs)Period 1: Day 1 to Day 4; Period 2: Day 1 to Day 10 + 3 days of end of study (EOS) period
Part B: number of participants with TEAEsPeriod 1: Day 1 to Day 4; Period 2: Day 1 to Day 12 + 8-10 days of end of study (EOS) period
Part A: SAR443820: Maximum plasma concentration observed (Cmax)Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10

Trial Locations

Locations (1)

Nucleus Network Site Number : 8400001

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Saint Paul, Minnesota, United States

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