Skip to main content
OpenTrials
Completed

NCT Number: NCT05049343

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

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

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Healthy Volunteer

Age range

21 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Sage Investigational Site

Newark, New Jersey, 07103, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

SAGE-904

Drug

SAGE-904 oral solution.

Placebo

Drug

Placebo oral solution.

ketamine

Drug

Ketamine intravenous (IV) infusion.

Primary outcomes

  1. 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

    Time frame: Pre-dose and post-dose on Days 1 and 11

    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).

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

    Time frame: Pre-dose and post-dose on Days 1 and 11

    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.

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

    Time frame: Pre-dose and post-dose on Days 1 and 11

    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.

  4. 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

    Time frame: Pre-dose and post-dose on Days 1 and 11

    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.

Secondary outcomes

  1. Number of Participants with Treatment Emergent Adverse Events (TEAEs)

    Time frame: Up to Day 25

    An adverse event (AE) is any untoward medical occurrence in a patients or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE with onset after the start of investigational product (IP), or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.

Sponsors and collaborators

Lead sponsor

Supernus Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Phase 1, Double-Blind, Placebo-Controlled Crossover Study of SAGE-904 Using a Ketamine Challenge to Evaluate Electrophysiology, Safety, Tolerability, and Pharmacokinetics in Healthy Participants

Important dates

Study start
2021
Primary completion
2021
Study completion
2021
First posted
Sep 20, 2021
Registry last updated
Sep 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.