First-in-man Study of Single and Multiple Ascending Doses of a New Drug for Neurological Disorders

Study Overview
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Brief Summary
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The primary purpose of this first-in-man study is to investigate whether a new drug for neurological disorders is safe and well-tolerated when administered orally to healthy adults

Official Title
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Single-center, Double-blind, Randomized, Placebo-controlled, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics (Including Food Effect), and Pharmacodynamics of an Oral Drug for Neurological Disorders in Healthy Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: AC-082
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key inclusion Criteria: Signed informed consent Healthy on the basis of physical examination,12-lead electrocardiogram and laboratory tests Males and females of non-childbearing potential, aged between 18 and 60 years (all inclusive) Women must have a negative serum pregnancy test at Screening and a negative urine pregnancy test predose on Day -1 Body mass index (BMI) between 18.0 and 29.9 kg/m2 (inclusive) Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) between 90-140 mmHg, 50-90 mmHg and 50-90 bpm (all inclusive), respectively Key exclusion Criteria: History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study treatment Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions Any circumstances or conditions, which, in the opinion of the Investigator, may affect full participation in the study or compliance with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AC-082, Single Ascending Dose<br>Subjects receive AC-082 at different single dose levels in a sequential manner, starting from 10 mg (number of cohorts and dose levels will depend on the safety and pharmacokinetic results of the previous cohort). Each subject can participate in only one dose level | Drug: AC-082<br>* Hard gelatin capsules for oral administration<br>|
| Placebo Comparator: Placebo, Single Ascending Dose<br>Subjects receive a single dose of the matched placebo | Drug: Placebo<br>* Matched placebo capsules for oral administration<br>|
| Experimental: AC-082, Multiple Ascending Dose<br>Subjects receive AC-082 at different dose levels for 4 consecutive days in a sequential manner (dose levels and duration to be adapted according to the results of the single ascending dose cohorts). Each subject can participate in only one dose level | Drug: AC-082<br>* Hard gelatin capsules for oral administration<br>|
| Placebo Comparator: Placebo, Multiple Ascending Dose<br>Subjects receive the matched placebo for 4 days | Drug: Placebo<br>* Matched placebo capsules for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | Treatment-emergent adverse events and treatment-emergent serious adverse events | Up to end of study (up to Day 11) | 
| Changes from baseline in vital signs | Vital signs include diastolic and systolic blood pressure and pulse rate | Up to end of study (up to Day 11) | 
| Changes from baseline in ECG variables | ECG variables are to be recorded at rest using a standard 12-lead ECG | Up to end of study (up to day 11) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) following single ascending doses | Cmax is derived from the observed plasma concentration-time curves | From pre-dose on Day 1 to 96 hours post dose | 
| Time to reach Cmax (tmax) following single ascending doses | tmax is derived from the observed plasma concentration-time curves | From pre-dose on Day 1 to 96 hours post dose | 
| Terminal half-life [t(1/2)] following single ascending doses |  | From pre-dose on Day 1 to 96 hours post dose | 
| Area under the plasma concentration-time curve (AUC) following single ascending doses | AUC is defined for the time intervals from zero to time t of the last measured concentration above the limit of quantification [AUC(0-t)] and from zero to infinity [AUC(0-inf)] | From pre-dose on Day 1 to 96 hours post dose | 
| Maximum plasma concentration (Cmax) following multiple ascending doses |  | Up to 96 hours following the last dose administration on Day 4 | 
| Time to reach Cmax (tmax) following multiple ascending doses |  | Up to 96 hours following the last dose administration on Day 4 | 
| Terminal half-life [t(1/2)] following multiple ascending doses | t(1/2) on the last day of dosing | Up to 96 hours following the last dose administration on Day 4 | 
| Area under the plasma concentration-time curve during a dosing interval (AUCtau) | AUCtau is the area under the plasma concentration-time curve during a dosing interval | Day 1 and Day 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy subjects, first-in-man, safety