A Study to Assess the Electrophysiology, Safety, Tolerability, and Pharmacokinetics of SAGE-718 Using a Ketamine Challenge in Healthy Subjects

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: SAGE-718; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Sage Investigational Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Sage Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 12-lead electrocardiograms (ECGs) including PR interval, QT interval, QTc interval, QTcF, and rhythm abnormalities	Observed values and change from baseline in ECGs in patients post study drug administration	Between Baseline and Day 12
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.	Observed values and change from baseline in EEGs in patients post study drug administration	Between Baseline and Day 12
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 changes from baseline in Brief Psychiatric Rating Scale (BPRS).		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 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

Collaborators and Investigators

• Sponsor: Sage Therapeutics

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2018
• Primary Completion (Actual): December 17, 2018
• Study Completion (Actual): January 2, 2019

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: December 7, 2018
• First Posted (Actual): December 11, 2018

Study Record Updates

• Last Update Posted (Actual): January 31, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 718-EXM-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No