Clinical trial NCT03771586: A Study to Assess the Electrophysiology, Safety, Tolerability, and Pharmacokinetics of SAGE-718 Using a Ketamine Challenge in Healthy Subjects
Official title: A Phase 1, Double-blind, Placebo-controlled Crossover Study of SAGE-718 Using a Ketamine Challenge, to Evaluate the Electrophysiology, Safety, Tolerability, and Pharmacokinetics in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Sage Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-12-11
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Between Day 1 and Day 11
Secondary outcomes:
measure: Safety and tolerability of SAGE-718-alone and in combination with ketamine, as assessed by the incidence of adverse events (AEs)/serious AEs (SAEs).
timeFrame: Between Baseline and Day 27
measure: 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
timeFrame: Between Baseline and Day 12
measure: 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.
timeFrame: Between Baseline and Day 12
measure: 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).
timeFrame: Between Baseline and 27 days
measure: Safety and tolerability of SAGE-718-alone and in combination with ketamine, as assessed by changes from baseline in Brief Psychiatric Rating Scale (BPRS).
timeFrame: Between Day 1 and Day 11
measure: 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).
timeFrame: Between Day 1 and Day 11
measure: 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).
timeFrame: Between Day 1 and Day 11
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Sage Investigational Site
state: California
city: Berlin
country: United States
facility: Sage Investigational Site
state: New Jersey
Study officials:
References: