A Study to Assess the Electrophysiology, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Response Using Magnetic Resonance Imaging of SAGE-718 Using a Ketamine Challenge in Healthy Subjects

Study Overview
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Brief Summary
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This study is a phase 1, double-blind, placebo-controlled crossover study of SAGE-718 using a ketamine challenge, to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic response using magnetic resonance imaging in healthy subjects

Official Title
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A PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CROSSOVER STUDY OF SAGE-718 USING A KETAMINE CHALLENGE, TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMIC RESPONSE USING MAGNETIC RESONANCE IMAGING IN HEALTHY SUBJECTS

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: SAGE-718
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is willing and able to provide 2 forms of identification; at least 1 must have a photo. Subject has a body weight ≥50 kg and body mass index ≥18.0 and ≤30.0 kg/m2 at screening. Subject is healthy with no history or evidence of clinically relevant medical disorders as determined by the Investigator. Exclusion Criteria: Subject has a history or presence of any psychiatric disease or condition including suicidal ideation or behavior, has answered YES to any question on the C-SSRS at screening or admission, or is currently at risk of suicide in the opinion of the Investigator Subject has a history or presence of a neurologic disease or condition, including but not limited to epilepsy, closed head trauma with clinically significant sequelae, or a prior seizure. Subject has a family history of epilepsy. Subject has evidence of any metal in the body that may be contraindicated for receiving an MRI. This includes, but is not limited to: cardiac pacemaker, surgical implants, previous accident resulting in metal or shrapnel lodged internally, tattoos inked with metallic dyes, or a history of metal work without using protective eyewear. Subject has claustrophobia or a history of claustrophobia. Subject is unable or unwilling to remove piercings and/or jewelry that contain metal.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAGE-718<br> | Drug: SAGE-718<br>* SAGE-718 in combination with Ketamine<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo in combination with Ketamine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glutamate and glutamine (GLX) in the anterior cingulate cortex (ACC), hippocampus, and pons as measured with magnetic resonance spectroscopy (MRS) |  | Between Day 1 and Day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glutamate in the ACC, hippocampus, and pons, as measured with MRS |  | Between Day 1 and Day 11 | 
| Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by incidence of adverse events (AEs)/serious AEs (SAEs) |  | Between Baseline and Day 27 | 
| Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by electroencephalograms (EEGs) | Observed values and change from baseline in EEGs in patients post study drug administration | Between Baseline and Day 27 | 
| Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by electrocardiograms (ECGs) | Observed values and change from baseline in ECGs in patients post study drug administration | Between Baseline and Day 27 | 
| Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) |  | Between Baseline and Day 27 | 
| Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Brief Psychiatric Rating Scale (BPRS) |  | Between Baseline and Day 27 | 
| Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Clinician Administered Dissociative State Scale (CADSS) |  | Between Baseline and Day 27 | 
| Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Observer's Assessment of Alertness and Sedation (OAAS) |  | Between Baseline and Day 27 |