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

• ClinicalTrials.gov Identifier: NCT05049343
• Recruitment Status: Completed
• First Posted: September 20, 2021
• Last Update Posted: January 21, 2022
• Sponsor: Sage Therapeutics
• Information provided by (Responsible Party): Sage Therapeutics

Tracking Information

• First Submitted Date: September 10, 2021
• First Posted Date: September 20, 2021
• Last Update Posted Date: January 21, 2022
• Actual Study Start Date: September 21, 2021
• Actual Primary Completion Date: November 20, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 10, 2021)

• 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).
• 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.
• 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.
• 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 10, 2021)

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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of SAGE-904 Using a Ketamine Challenge to Evaluate Electrophysiology, Safety, Tolerability, and Pharmacokinetics in Healthy Participants
• Official 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Healthy Volunteer

Intervention

• Drug: SAGE-904
  SAGE-904 oral solution.
• Drug: Placebo
  Placebo oral solution.
• Drug: Ketamine
  Ketamine intravenous (IV) infusion.

Study Arms

• Experimental: SAGE-904 then Placebo
  SAGE-904 in combination with ketamine, followed by a washout period, followed by placebo in combination with ketamine.
  Interventions:

  • Drug: SAGE-904
  • Drug: Placebo
  • Drug: Ketamine
• Placebo Comparator: Placebo then SAGE-904
  Placebo in combination with ketamine, followed by a washout period, followed by SAGE-904 in combination with ketamine.
  Interventions:

  • Drug: SAGE-904
  • Drug: Placebo
  • Drug: Ketamine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 10, 2021): 22
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 3, 2021
• Actual Primary Completion Date: November 20, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05049343
• Other Study ID Numbers: 904-TRM-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

• Current Responsible Party: Sage Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Sage Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Sage Therapeutics
• Verification Date: January 2022