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)

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT05797753

Collaborator

(none)

Enrollment

Location

Arms

4.4

Actual Duration (Months)

3.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis (Healthy Volunteers)	Drug: SAR443820 Drug: SAR443820 Drug: Erythromycin ethyl succinate Drug: Itraconazole	Phase 1

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Single-center, Open-label, 2-part, 2-treatment Period, 1-sequence, Cross-over, Drug-drug Interaction Study to Investigate the Effect of Erythromycin on SAR443820 (Part A) and the Effect of Itraconazole on SAR443820 (Part B) in Healthy Adult Participants

Actual Study Start Date :

Feb 18, 2022

Actual Primary Completion Date :

Jul 1, 2022

Actual Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part-A, Period-1 Single dose of SAR443820 tablet on Day 1	Drug: SAR443820 Tablet by oral administration
Experimental: Part-A, Period-2 Single dose of SAR443820 tablet on Day 6, and erythromycin ethyl succinate (EES) three-time a day (TID) from Day 1 to Day 9	Drug: SAR443820 Tablet by oral administration Drug: Erythromycin ethyl succinate Tablet by oral administration
Experimental: Part-B, Period-1 Single dose of SAR443820 capsule on Day 1	Drug: SAR443820 Capsule by oral administration
Experimental: Part-B, Period-2 Single dose of SAR443820 capsule on Day 6, and Itraconazole once daily (QD) from Day 1 to Day 11	Drug: SAR443820 Capsule by oral administration Drug: Itraconazole Capsule by oral administration

Outcome Measures

Primary Outcome Measures

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]
Part B: SAR443820: AUClast [Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 12]
Part B: SAR443820: AUC [Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 12]

Secondary Outcome Measures

Part A: SAR443820: Maximum plasma concentration observed (Cmax) [Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10]
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: Cmax [Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 12]
Part B: SAR443820: tmax [Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 12]
Part B: SAR443820: t1/2z [Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 12]
Part A: Erythromycin ethyl succinate concentrations [Period 2: Day 6 and Day 7]
Part A: Erythromycin base concentration [Period 2: Day 6 and Day 7]
Part B: Itraconazole: Cmax [Period 2: Day 6 and Day 7]
Part B: Itraconazole: AUClast [Period 2: Day 6 and Day 7]
Part B: Hydroxyitraconazole: Cmax [Period 2: Day 6 and Day 7]
Part B: Hydroxyitraconazole: AUClast [Period 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 TEAEs [Period 1: Day 1 to Day 4; Period 2: Day 1 to Day 12 + 8-10 days of end of study (EOS) period]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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