Study of SAGE-904 Using a Ketamine Challenge to Evaluate Electrophysiology, Safety, Tolerability, and Pharmacokinetics in Healthy Participants

NCT05049343 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 904-TRM-101
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to determine functional target engagement of SAGE-904 using electrophysiological paradigms before and after ketamine administration.

Conditions

Healthy Volunteer

Keywords

Healthy Volunteer; SAGE-904; Ketamine

Outcome Measures

Primary Outcomes (4)

• Change in Electrophysiological Parameter: Auditory Evoked Potential (AEP) in a Single-stimulus Paradigm Before and After Ketamine Infusion in Participants Receiving SAGE-904 Versus (vs) Participants Receiving Placebo

  AEP variables will include individual amplitudes of N100 and P200 responses and the derived peak-to-peak amplitude of these responses (N100-P200) in microvolts (µV).

  Pre-dose and post-dose on Days 1 and 11

• Change in Electrophysiological Parameter: Mismatch Negativity (MMN) Before and After Ketamine Infusion in Participants Receiving SAGE-904 vs Participants Receiving Placebo

  MMN is a response to nonmatching sounds in a series of matching sounds. Two tones of the same frequency and sound intensity, but differing in duration, will be sequentially presented to the participant through insert earphones. MMN amplitude will be measured from the peak of a mid-latency negative voltage deflection in the difference waveform representing the response to deviant stimuli in µV.

  Pre-dose and post-dose on Days 1 and 11

• Change in Electrophysiological Parameter: Auditory Steady-state Response (ASSR) Power Before and After Ketamine Infusion in Participants Receiving SAGE-904 vs Participants Receiving Placebo

  ASSR is used to assess the integrity of sensory pathways including cortical processing. ASSR will be measured at midline central electrode (Cz) of electroencephalogram (EEG) to assess the response in hertz (Hz). In ASSR, streams of "click" stimuli will be presented at a rate of 40 Hz while the participant will be instructed to fix their gaze on a white cross displayed on a computer monitor.

  Pre-dose and post-dose on Days 1 and 11

• Change in Electrophysiological Parameter: P300 in a Target Detection Paradigm as Assessed by Auditory Response Before and After Ketamine Infusion in Participants Receiving SAGE-904 vs Participants Receiving Placebo

  Improvement of the P300 auditory response time in milliseconds using P300 AEP in a target detection paradigm by an increase in amplitude and/or a decrease in latency will be analyzed. In this paradigm, 2 tones of the same sound intensity, but differing in frequency, are sequentially presented to the participant through insert earphones. The "standard" (low frequency) stimuli will be presented on the majority of trials, with a "target" (high frequency) stimuli presented periodically at random. The participant is told to listen for the "target" stimuli and press a button on the handset as fast as they can. The endpoint variables of P300 amplitude and latency in correlation with the button press reaction time will be used to assess the response time.

  Pre-dose and post-dose on Days 1 and 11

Secondary Outcomes (1)

• Number of Participants with Treatment Emergent Adverse Events (TEAEs)

  Up to Day 25

Study Arms (2)

SAGE-904 then Placebo

EXPERIMENTAL

SAGE-904 in combination with ketamine, followed by a washout period, followed by placebo in combination with ketamine.

Drug: SAGE-904; Drug: Placebo; Drug: Ketamine

Placebo then SAGE-904

PLACEBO COMPARATOR

Placebo in combination with ketamine, followed by a washout period, followed by SAGE-904 in combination with ketamine.

Drug: SAGE-904; Drug: Placebo; Drug: Ketamine

Interventions

SAGE-904 DRUG

SAGE-904 oral solution.

Placebo then SAGE-904; SAGE-904 then Placebo

Placebo DRUG

Placebo oral solution.

Placebo then SAGE-904; SAGE-904 then Placebo

Ketamine DRUG

Ketamine intravenous (IV) infusion.

Placebo then SAGE-904; SAGE-904 then Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant is willing and able to provide 2 forms of identification; at least 1 must have a photo
• Participant has a body weight ≥50 kilograms (kg) and body mass index ≥18.0 and ≤30.0 kilograms per square meter (kg/m\^2) at screening
• Participant is healthy with no history or evidence of clinically relevant medical disorders as determined by the investigator
• Participant has the ability to tolerate the electrode headset for the duration of the testing session

You may not qualify if:

• Participant has a history or presence of any psychiatric disease or condition including suicidal ideation or behavior, has answered YES to any question on the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening or admission, or is currently at risk of suicide in the opinion of the Investigator
• Participant has a history or presence of a neurologic disease or condition, including, but not limited to, epilepsy, closed head trauma with clinically significant (CS) sequelae, or a prior seizure
• Participant has a family history of epilepsy
• Participant has a history, presence, and/or current evidence of serologic positive results for Hepatitis B and C, human immunodeficiency virus (HIV) 1 or 2
• Participant 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 pharmacokinetic (PK) sample or affect the ability to receive the ketamine infusions
• Participant has had previous exposure to or is known to be allergic to ketamine or any of its excipients

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead

Study Sites (1)

Sage Investigational Site

Newark, New Jersey, 07103, United States

Location

MeSH Terms

Interventions

Ketamine

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2021
• First Posted: September 20, 2021
• Study Start: September 21, 2021
• Primary Completion: November 20, 2021
• Study Completion: December 3, 2021
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)