Clinical trial NCT03770780: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Sage Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-12-10
Enrollment: 19
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 SAGE-718 using a ketamine challenge, to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic response using magnetic resonance imaging in healthy subjects


Eligibility criteria: 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.

Primary outcomes:
measure: Change in glutamate and glutamine (GLX) in the anterior cingulate cortex (ACC), hippocampus, and pons as measured with magnetic resonance spectroscopy (MRS)
timeFrame: Between Day 1 and Day 11
Secondary outcomes:
measure: Change in glutamate in the ACC, hippocampus, and pons, as measured with MRS
timeFrame: Between Day 1 and Day 11
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by 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 electroencephalograms (EEGs)
timeFrame: Between Baseline and Day 27
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by electrocardiograms (ECGs)
timeFrame: Between Baseline and Day 27
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Between Baseline and Day 27
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Brief Psychiatric Rating Scale (BPRS)
timeFrame: Between Baseline and Day 27
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Clinician Administered Dissociative State Scale (CADSS)
timeFrame: Between Baseline and Day 27
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Observer's Assessment of Alertness and Sedation (OAAS)
timeFrame: Between Baseline and Day 27
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: