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

• Sponsor: Sage Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03770780
• Collaborator: (none)
• Enrollment: 19
• Locations: 2
• Arms: 2
• Actual Duration (Months): 4.3
• Patients Per Site: 9.5
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteer	Drug: SAGE-718; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: Nov 12, 2018
• Actual Primary Completion Date: Mar 8, 2019
• Actual Study Completion Date: Mar 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SAGE-718	Drug: SAGE-718; SAGE-718 in combination with Ketamine
Placebo Comparator: Placebo	Drug: Placebo; Placebo in combination with Ketamine

Outcome Measures

Primary Outcome Measures

1. 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

1. Change in glutamate in the ACC, hippocampus, and pons, as measured with MRS [Between Day 1 and Day 11]

2. 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]

3. 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

4. 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

5. 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]

6. 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]

7. 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]

8. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sage Investigational Site	Long Beach	California	United States	90806
2	Sage Investigational Site	Berlin	New Jersey	United States	08009

Sponsors and Collaborators

• Sage Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT03770780
• Other Study ID Numbers: 718-EXM-102
• First Posted: Dec 10, 2018
• Last Update Posted: Feb 4, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Feb 4, 2022