Study of SAGE-904 Using a Ketamine Challenge to Evaluate... | NCT05049343 | Trialant

Study of SAGE-904 Using a Ketamine Challenge to Evaluate... | NCT05049343 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants with Treatment Emergent Adverse Events (TEAEs)	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.