Amyotrophic Lateral Sclerosis (Healthy Volunteers)
Conditions
Brief summary
This is a Phase 1, single-center study conducted in 2 parts: Part 1a, single ascending dose (SAD-TDU16519): Double-blind, randomized, placebo-controlled sequential ascending single oral doses including up to 6 cohorts. Each cohort will include 8 participants (6 receiving SAR443820 and 2 placebo). Part 1b (TDU16519): - Open label, single SAR443820 dose in one or two separated cohort(s) for SAR443820 measurements in CSF and in plasma. Part 2, multiple ascending dose (MAD -TDR16520): Double-blind, randomized, placebo-controlled, sequential ascending repeated oral doses for 14 days, including up to 4 cohorts. Each cohort will include 10 participants (8 receiving SAR443820 and 2 placebo).
Detailed description
The duration of the study for a participant will include: Screening Period: up to 28 days Part 1a: Treatment in fasted condition: 1 day (Day 1). Study observation Period from Day -2/Day -1 to Day 3. Follow-up with the end of study: from Day 5 to Day 7. Total duration from screening per participant: up to 5 weeks. Part 1b: Treatment in fed condition: 1 day (Day 1). Study observation Period from Day -1/Day1 to Day 2. Follow-up with the end of study: from Day 5 to Day 7. Total duration from screening per participant: up to 5 weeks. Part 2: Treatment: 14 days (Day 1 to Day 14). Study observation Period from Day -2/Day -1 to Day 17. Follow-up with the end of study: from Day 19 to Day 21. Total duration from screening per participant: up to 7 weeks.
Interventions
DRUGSAR443820
Capsule / Oral
DRUGPlacebo
Matching Capsule / Oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Part 1b with open label study design
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Male and/or female participant, between 18 and 55 years of age, inclusive. 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 and complete physical examination). Having given written informed consent prior to undertaking any study-related procedure. Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order.
Exclusion criteria
Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteo-muscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness. Personal medical history of seizure. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month). 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 vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion. Positive result for hepatitis B, C or HIV Positive result on urine drug screen Positive alcohol test. Any consumption of citrus fruits or their juices within 5 days before inclusion. Current psychiatric disorder, suicidal ideation in the previous 6 months (as assessed by the C-SSRS), or a lifetime suicide attempt. Additional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Parts 1a and 1b: Number of participants with adverse events | Day1 up to Day 7 (end of study visit) |
| Part 2: Number of participants with adverse events | Day1 up to Day 21 (end of study visit) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1a and 1b : Assessment of pharmacokinetic parameter of SAR443820: AUC in plasma | Day1 | Parts 1a and 1b: Area under the plasma concentration versus time |
| Parts 1a and 1b : Assessment of pharmacokinetic parameter of SAR443820: t1/2z in plasma | Day1 | Terminal half-life in plasma |
| Part1b: SAR443820 concentrations in cerebrospinal fluid (CSF) samples | Day1 | Part 1b: CSF to plasma concentration ratio |
| Part 2: Assessment of pharmacokinetic parameter of SAR443820: Cmax in plasma | Day1 and Day14 | Part 2: Maximum plasma concentration |
| Parts 1a and 1b: Assessment of pharmacokinetic parameter of SAR443820: Cmax in plasma | Day1 | Parts 1a and 1b: Maximum plasma concentration |
| Part 2: Assessment of pharmacokinetic parameter of SAR443820: AUC tau in plasma | Day1 and Day14 | Part 2: Area under the plasma concentration versus time during a dosing interval |
| Part 2 Assessment of pharmacokinetic parameter of SAR443820: t1/2z in plasma | Day14 | Terminal half-life in plasma |
| Part 2: Day14/Day1 of 4β-hydroxycholesterol ratio in plasma | Day1 and Day14 | D14/D1 of 4β-hydroxycholesterol ratio |
| Part 2: Assessment of pharmacokinetic parameter of SAR443820: tmax in plasma | Day1 and Day14 | Part 2: Time to reach Cmax |
| Parts 1a and 1b: Assessment of pharmacokinetic parameter of SAR443820: tmax in plasma | Day 1 | Parts 1a and 1b: time to reach Cmax |
Countries
United States
Outcome results
None listed