Healthy Volunteer
Conditions
Brief summary
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
Interventions
DRUGSAGE-718
SAGE-718 in combination with Ketamine
DRUGPlacebo
Placebo in combination with Ketamine
Sponsors
Supernus Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subject is willing and able to provide 2 forms of identification; at least 1 must have a photo. 2. Subject has a body weight ≥50 kg and body mass index ≥18.0 and ≤30.0 kg/m2 at screening. 3. Subject is healthy with no history or evidence of clinically relevant medical disorders as determined by the Investigator.
Exclusion criteria
1. 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 2. 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. 3. Subject has a family history of epilepsy. 4. 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. 5. Subject has claustrophobia or a history of claustrophobia. 6. Subject is unable or unwilling to remove piercings and/or jewelry that contain metal.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | Between Baseline and Day 27 | Observed values and change from baseline in EEGs in patients post study drug administration |
| Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by electrocardiograms (ECGs) | Between Baseline and Day 27 | Observed values and change from baseline in ECGs in patients post study drug administration |
| 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 | — |
Countries
United States
Outcome results
None listed