A Study to Assess NEU-411 in Healthy Participants

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose (SAD), food effect (FE),multiple ascending dose (MAD), of orally administered NEU-411 in healthy subjects

Detailed Description
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Up to five (5) single-ascending oral doses will be administered to 40 healthy adult male or female subjects (aged 18-80 years, inclusive). Escalation to the next higher dose level may occur only after evaluation of the safety and PK results of the previous dose level (at least 6 evaluable subjects). Within each cohort, 6 subjects will receive one dose of NEU-411, and 2 subjects will receive one dose of matching placebo. Dose levels may be revised based on available safety and PK data. Food effect will evaluate approximately 8 subjects in a fasted versus fed state. Multiple ascending oral doses will be administered up to 24 healthy subjects (aged 18 - 80 years, inclusive) in 3 sequential dosing groups (8 subjects in each dosing group). Six (6) subjects will receive NEU-411 and two (2) subjects will receive matching placebo in each dosing group (cohort) for 7 days. Escalation to the next higher dose level may occur only after evaluation of the safety and PK results of the previous dose level (at least 6 evaluable subjects). Dose levels may be revised based on available safety and PD data. Multiple oral dosing will be administered in up to 39 healthy subjects in 3 sequential dosing groups (13 subjects across 3 dosing groups) over 28 days.

Official Title
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A Phase 1, Single and Multiple Ascending Dose and Food Effect Study of NEU-411 Administered Orally to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: NEU-411
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects for standard cohorts must be 18-80 years, inclusive, at the time of signing the informed consent; Subjects who are in good general health with no clinically relevant abnormalities based on the medical history, physical examinations, neurological examinations, clinical laboratory evaluations (hematology and clinical chemistry) Subjects who have a body mass index (BMI) of 18-32 kg/m2(inclusive); Male subjects are eligible to participate if they are rendered surgically sterile (at least 6 months), or agree to the following during the study and for at least 30 days after the last dose of study drug: Refrain from donating sperm; AND, 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 Agree to use a male condom (contraception/barrier) and should also be advised of the benefit for a female partner to use an acceptable, highly effective method of contraception as a condom may break or leak when having sexual intercourse; • Female subjects are eligible to participate if they are not pregnant or breastfeeding, subject to one of the following: Women of childbearing potential (WOCBP), defined as women physiologically capable of becoming pregnant, must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test on Day -1; WOCBP must agree to use an acceptable, highly effective contraceptive method from Screening until 30 days after the last dose of study treatment (see Section 11.3); OR Menopausal women must have an elevated serum follicle-stimulating hormone level (FSH) level at Screening; if the FSH is not elevated, they are considered to be of childbearing potential (unless permanently sterile) and must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1 Exclusion Criteria: History of clinically significant hematological, renal, pancreatic, gastrointestinal, hepatic, cardiovascular, metabolic, endocrine, immunological, allergic disease, or other major disorders History of clinically significant abnormal chest x-ray Clinically significant neurologic disorder Contraindications to undergo a lumbar puncture (only for subjects participating in the MAD)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEU-411<br>Part A: Single-ascending dose cohorts; food effect; Part B: Multiple-ascending dose cohorts (7 days) | Drug: NEU-411<br>* Oral Doses<br>|
| Placebo Comparator: Placebo<br>Part A: Single-ascending dose cohorts; food effect; Part B: Multiple-ascending dose cohorts (7 days) | Drug: Placebo<br>* Oral Doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety and tolerability of single dosing, food effect and multiple oral doses of NEU-411 in healthy subjects | Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to 7 days of dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter | The maximum concentration (Cmax) at steady state in plasma | Up to 7 days of dosing | 
| PK parameter | The area under the concentration-time curve from zero to infinity (AUC0-inf) in plasma | Up to 7 days of dosing | 
| PK parameter | The time to reach maximum concentration (tmax) in plasma | Up to 7 days of dosing | 
| PK parameter | Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) in plasma | Up to 7 days of dosing | 
| PK parameter | Apparent terminal elimination half-life (t1/2) in plasma | Up to 7 days of dosing | 
| PK parameter | The terminal elimination rate constant (λZ) with the respective half-life (t½) in plasma | Up to 7 days of dosing | 
| PK parameter | The oral clearance (CL/F) | Up to 7 days of dosing | 
| PK parameter | The volume of distribution (Vd/F) | Up to 7 days of dosing | 
| PK parameter | The area under the concentration-time curve over a dosing interval (AUC0-τ) in plasma (multiple dosing only) | Up to 7 days of dosing |