A study in healthy male adult participants to assess how much test medicine (SAR443820) is taken up, broken down and removed by the body when given in a liquid form by mouth.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Research & Development

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

2 Jun 2023 → 17 Jul 2023

Decision date (initial)

2023-05-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Sanofi Aventis Recherche & Développement

External identifiers

EU CT number

2022-502534-23-00

WHO UTN

U1111-1280-4755

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Others

To determine the excretion balance after oral administration of [14C]-SAR443820 in healthy male Participants


To determine the pharmacokinetics of [14C]-drug material (in blood and plasma), SAR443820 (in plasma) and its contribution to the overall exposure of [14C]-drug material


To collect samples (plasma and excreta) in order to determine the metabolic pathways of SAR443820 and identify the chemical structures and main excretion routes of the main metabolites

Secondary objectives 1

1. To assess tolerability and safety of SAR443820

Conditions and MedDRA coding

amyotrophic lateral sclerosis (ALS)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male participants, 18 to 55 years of age inclusive, at the time of signing the informed consent.
2. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG.
3. Vital signs after 5 minutes (at a minimum) resting in supine position within the following ranges: - 95 mmHg ≤ systolic blood pressure (SBP) <140 mmHg - 45 mmHg < diastolic blood pressure (DBP) <90 mmHg - 45 bpm < heart rate (HR) <100 bpm
4. Standard 12-lead ECG parameters after 5 minutes (at a minimum) resting in supine position in the following ranges: 120 ms
5. Laboratory parameters within the normal range (or defined screening threshold for the Investigator site), unless the Investigator considers an abnormality to be clinically irrelevant for healthy participants; however, serum creatinine, alkaline phosphatase, hepatic enzymes (AST, ALT), should not exceed 1.25-fold the ULN for each.
6. Body weight within 60.0 and 90.0 kg inclusive and body mass index (BMI) within the range 18.0 to <30.0 kg/m2
7. Male Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a) Male participants Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last administration of study intervention: - Refrain from donating sperm Plus either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR - Must agree to use contraception/barrier as detailed below A male condom; the participant should also be advised of the benefit for a female partner to use a highly effective method of contraception (as described in Appendix 4 [Section 10.4] Contraceptive and barrier guidance) as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. b) Female participants: Not applicable.
8. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1) of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
9. Normal renal function as expressed by body surface area-normalized glomerular filtration rate (GFR) >90 mL/min/1.73 m2 as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (9, 10).
10. Must have regular bowel movements (ie, average stool production of ≥1 per 48-hour interval and ≤3 stools per day).

Exclusion criteria 23

1. Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness.
2. Medical history of seizure (history of febrile seizure during childhood is allowed).
3. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month).
4. Blood donation, any volume (usually approximately 500 mL), within 3 months before inclusion (Day 1).
5. Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥30 mmHg within 3 minutes when changing from supine to standing position.
6. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician. Participants with known hypersensitivity to any component of the IMP formulation or allergic disease diagnosed and treated by a physician.
7. History or presence of drug or alcohol abuse (alcohol consumption more than 24 units per week on a regular basis).
8. Smoking regularly more than 5 cigarettes or equivalent per day, unable to avoid smoking, tobacco, or other nicotine-containing product (such as lozenges or vaporizers) on Day -1 and Day 1. Excessive consumption of beverages containing xanthine bases (more than 6 cups or glasses per day). Intake of poppy seeds within 48 hours prior to drug screens (to avoid false-positive drug screen results).
9. Any medication (including supplements or herbal medicines such as St John’s Wort) within 14 days (or 3 weeks if the concomitant drug is a potential enzyme inducer) or within 5 times the elimination half-life or pharmacodynamic half-life of the medication as far as known (whichever is longer) before inclusion (Day 1) (see Section 6.9); any non-live COVID-19 vaccine within the last 2 weeks before inclusion (Day 1), any live attenuated vaccine within the last 28 days before inclusion (Day 1), and any other non-vaccine biological drugs given within 4 months before inclusion (Day 1). Property of the Sanofi group - strictly confidential
10. Past participation in previous clinical studies on SAR443820. Current enrollment OR past participation in another investigational study within 30 days prior to inclusion (or inclusion within 5 times the elimination half-life or pharmacodynamic half-life, as far as known, of the investigational drug received in another investigational study), or in 4 or more other investigational drug studies within 12 months prior to inclusion (Day 1).
11. Positive result on any of the following tests: hepatitis B surface antigen (HBs Ag), anti-hepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2 Ab).
12. Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
13. Positive urine alcohol test.
14. Positive SARS-CoV-2 test (measured by Real-time Reverse Transcriptase Polymerase Chain Reaction [RT-PCR]).
15. Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
16. Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
17. Participants who are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with Section 1.61 of the International Council for Harmonisation [ICH]-Good Clinical Practice [GCP] Ordinance E6).
18. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.
19. Any country-related specific regulation that would prevent the participant from entering the study – see Appendix 8 (Section 10.8) of the protocol (country-specific requirements).
20. Any consumption of citrus fruits (grapefruit, Seville orange, etc) or their juices within 5 days before inclusion (Day 1).
21. Exposure to radiation for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton [excluding spinal column]), and/or during work, and/or during participation in a trial with [14C]-radiolabeled medication (>0.1 MBq) in the 12 months preceding the study. Participation in a previous study with a micro-tracer dose (≤0.1 MBq) in the 3 months preceding the study.
22. Participants with [14C] in blood >lower limit of quantification (LLOQ) when using AMS at screening.
23. Participants who do not have suitable veins for multiple venipunctures/cannulation as assessed by the Investigator or delegate at screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint: Pharmacokinetics Pharmacokinetic data will be summarized using descriptive statistics for each appropriate matrix. The results of other primary endpoint analyses of plasma and excreta samples collected to determine the metabolic pathways of SAR443820 and identify the chemical structures and main excretion routes of the main metabolites will be documented separately.

Secondary endpoints 1

1. Safety analysis (adverse events [AEs], laboratory parameters, vital signs, and electrocardiograms [ECGs]) will be based on the review of individual values and descriptive statistics.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Research & Development

Sponsor organisation

Sanofi-Aventis Research & Development

Address

1 Avenue Pierre Brossolette

City

Chilly Mazarin

Postcode

91380

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 6

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications