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SAGE-904

Phase 1

Healthy Volunteer | Small molecule | Other |Supernus Pharmaceuticals, Inc.|Last Updated: Sep 17, 2025

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment22
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT05049343Study of SAGE-904 Using a Ketamine Challenge to Evaluate Electrophysiology, Safety, Tolerability, and Pharmacokinetics in Healthy ParticipantsPHASE1 COMPLETED 22Sep 21, 2021Dec 3, 2021Sep 17, 20251 United States
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Study Endpoints
Primary Endpoints
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
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).

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

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

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
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 Endpoints
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Up to Day 25
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelCROSSOVER
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
SAGE-904 then PlaceboEXPERIMENTALSAGE-904 in combination with ketamine, followed by a washout period, followed by placebo in combination with ketamine.
Placebo then SAGE-904PLACEBO_COMPARATORPlacebo in combination with ketamine, followed by a washout period, followed by SAGE-904 in combination with ketamine.
Interventions
NameTypeDescription
SAGE-904DRUGSAGE-904 oral solution.
PlaceboDRUGPlacebo oral solution.
KetamineDRUGKetamine intravenous (IV) infusion.
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Eligibility Criteria
Age Range21 Years — 55 Years
SexALL
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: 1. Participant is willing and able to provide 2 forms of identification; at least 1 must have a photo 2. 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 3. Participant is healthy with no histo...

Countries:United States
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