Clinical trial NCT05797753: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Healthy Volunteer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-04-04
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Part A: SAR443820: Area under the plasma concentration from time zero to the last concentration above the limit of quantification (AUClast)
timeFrame: Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10
measure: Part A: SAR443820: Area under the plasma concentration (AUC)
timeFrame: Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10
measure: Part B: SAR443820: AUClast
timeFrame: Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 12
measure: Part B: SAR443820: AUC
timeFrame: Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 12
Secondary outcomes:
measure: Part A: SAR443820: Maximum plasma concentration observed (Cmax)
timeFrame: Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10
measure: Part A: SAR443820: Time to reach Cmax (tmax)
timeFrame: Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10
measure: Part A: SAR443820: Terminal half-life (t1/2z)
timeFrame: Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 10
measure: Part B: SAR443820: Cmax
timeFrame: Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 12
measure: Part B: SAR443820: tmax
timeFrame: Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 12
measure: Part B: SAR443820: t1/2z
timeFrame: Period 1: Day 1 to Day 3; Period 2: Day 6 to Day 12
measure: Part A: Erythromycin ethyl succinate concentrations
timeFrame: Period 2: Day 6 and Day 7
measure: Part A: Erythromycin base concentration
timeFrame: Period 2: Day 6 and Day 7
measure: Part B: Itraconazole: Cmax
timeFrame: Period 2: Day 6 and Day 7
measure: Part B: Itraconazole: AUClast
timeFrame: Period 2: Day 6 and Day 7
measure: Part B: Hydroxyitraconazole: Cmax
timeFrame: Period 2: Day 6 and Day 7
measure: Part B: Hydroxyitraconazole: AUClast
timeFrame: Period 2: Day 6 and Day 7
measure: Part A: number of participants with treatment emergent adverse events (TEAEs)
timeFrame: Period 1: Day 1 to Day 4; Period 2: Day 1 to Day 10 + 3 days of end of study (EOS) period
measure: Part B: number of participants with TEAEs
timeFrame: Period 1: Day 1 to Day 4; Period 2: Day 1 to Day 12 + 8-10 days of end of study (EOS) period
Other outcomes:
Locations:
city: Saint Paul
country: United States
facility: Nucleus Network Site Number : 8400001
state: Minnesota
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: