Healthy Volunteer
Conditions
Brief summary
This study is a phase 1, double-blind, placebo-controlled crossover study of single, oral dose of SAGE-718 using a ketamine challenge, to evaluate the electrophysiology, safety, tolerability, and pharmacokinetics 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 has a body weight ≥50 kg and body mass index ≥18.0 and ≤30.0 kg/m2 at screening. 2. If female, subject is post-menopausal (at least 12 months of spontaneous amenorrhea with confirmatory follicle stimulating hormone \>40 mIU/mL), or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, and/or hysterectomy). 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 obstructed venous access and/or has skin disease, rash, acne, or abrasion at venous access site that may affect the ability to obtain a PK sample or affect the ability to receive the ketamine infusions. 5. Subject has had previous exposure to or is known to be allergic to ketamine or any of its excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in the electrophysiological parameters, auditory evoked potentials, between pre- and post-ketamine infusion in subjects receiving SAGE-718 vs the change in parameters between pre- and post-ketamine infusion in subjects receiving placebo | Between Day 1 and Day 11 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of SAGE-718-alone and in combination with ketamine, as assessed by changes from baseline in 12-lead electrocardiograms (ECGs) including PR interval, QT interval, QTc interval, QTcF, and rhythm abnormalities | Between Baseline and Day 12 | 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 changes from baseline in electroencephalograms (EEGs) including Delta, Theta, Alpha, Beta. | Between Baseline and Day 12 | 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 changes from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS). | Between Baseline and 27 days | — |
| Safety and tolerability of SAGE-718-alone and in combination with ketamine, as assessed by the 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 changes from baseline in Clinician Administered Dissociative State Scale (CADSS). | Between Day 1 and Day 11 | — |
| Safety and tolerability of SAGE-718-alone and in combination with ketamine, as assessed by changes from baseline in Observer's Assessment of Alertness and Sedation (OAAS). | Between Day 1 and Day 11 | — |
| Safety and tolerability of SAGE-718-alone and in combination with ketamine, as assessed by changes from baseline in Brief Psychiatric Rating Scale (BPRS). | Between Day 1 and Day 11 | — |
Countries
United States
Outcome results
None listed