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

• Sponsor: Sage Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03771586
• Collaborator: (none)
• Enrollment: 22
• Locations: 2
• Arms: 2
• Actual Duration (Months): 3.3
• Patients Per Site: 11
• Patients Per Site Per Month: 3.3

Study Details

Study Description

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

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: Sep 24, 2018
• Actual Primary Completion Date: Dec 17, 2018
• Actual Study Completion Date: Jan 2, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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]

2. 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

3. 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

4. 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]

5. 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]

6. 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]

7. 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]

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 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.

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

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT03771586
• Other Study ID Numbers: 718-EXM-101
• First Posted: Dec 11, 2018
• Last Update Posted: Jan 31, 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
• Additional relevant MeSH terms: Ketamine

Study Results

No Results Posted as of Jan 31, 2022