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).
Study of SAGE-904 Using a Ketamine Challenge to Evaluate Electrophysiology, Safety, Tolerability, and Pharmacokinetics in Healthy Participants
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.
Intervention / Treatment
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SAGE-904 (DRUG)SAGE-904 oral solution.
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Placebo (DRUG)Placebo oral solution.
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Ketamine (DRUG)Ketamine intravenous (IV) infusion.
Condition or Disease
- Healthy Volunteer
Phase
Study Design
| Study type: | INTERVENTIONAL |
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| Status: | Completed |
| Study results: | No Results Available |
| Age: | 21 Years to 55 Years |
| Enrollment: | 22 (ACTUAL) |
| Allocation: | Randomized |
| Primary Purpose: | Treatment |
MaskingQUADRUPLE:
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Clinical Trial Dates
| Start date: | Sep 21, 2021 | ACTUAL |
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| Primary Completion: | Nov 20, 2021 | ACTUAL |
| Completion Date: | Dec 03, 2021 | ACTUAL |
| Study First Posted: | Sep 20, 2021 | ACTUAL |
| Last Updated: | Jan 20, 2022 |
Sponsors / Collaborators
Participant Groups
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SAGE-904 in combination with ketamine, followed by a washout period, followed by placebo in combination with ketamine.
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Placebo in combination with ketamine, followed by a washout period, followed by SAGE-904 in combination with ketamine.
Eligibility Criteria
| Sex: | All |
|---|---|
| Minimum Age: | 21 |
| Maximum Age: | 55 |
| Age Groups: | Adult |
| Healthy Volunteers: | Yes |
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 history or evidence of clinically relevant medical disorders as determined by the investigator
4. Participant has the ability to tolerate the electrode headset for the duration of the testing session
Exclusion Criteria:
1. 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
2. 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
3. Participant has a family history of epilepsy
4. 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
5. 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
6. Participant has had previous exposure to or is known to be allergic to ketamine or any of its excipients
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 history or evidence of clinically relevant medical disorders as determined by the investigator
4. Participant has the ability to tolerate the electrode headset for the duration of the testing session
Exclusion Criteria:
1. 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
2. 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
3. Participant has a family history of epilepsy
4. 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
5. 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
6. Participant has had previous exposure to or is known to be allergic to ketamine or any of its excipients
Primary Outcomes
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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.
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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.
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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
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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.
More Details
| NCT Number: | NCT05049343 |
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| Other IDs: | 904-TRM-101 |
| Study URL: | https://clinicaltrials.gov/study/NCT05049343 |
Last updated: Sep 29, 2023