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

Phase 1

Completed

• Conditions: Healthy Volunteer
• Interventions: Drug: Placebo; Drug: SAGE-718

• Registration Number: NCT03771586
• Lead Sponsor: Sage Therapeutics

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

Detailed Description

Not available

Study Timeline

• Study Start: 2018-09-24
• Study First Submitted: 2018-10-02
• Study First Submitted QC: 2018-12-07
• Study First Posted: 2018-12-11
• Primary Completion: 2018-12-17
• Study Completion: 2019-01-02
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-20
• Last Update Posted: 2022-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
SAGE-718	SAGE-718	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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 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

Trial Locations

Locations (1)

Sage Investigational Site; 🇺🇸 Berlin, New Jersey, United States