A Long-term Safety Study of Intranasal Esketamine in Treatment-resistant Depression
- UT Southwestern-Other
Madhukar Trivedi, M.D.
An Open-label Long-term Extension Safety Study of Intranasal Esketamine in Treatment-resistant Depression
The purpose of this study is to assess the safety and tolerability of intranasal esketamine in participants with treatment-resistant depression (TRD).
This is an open-label (the researchers and participants know the treatment the participant is receiving) long-term extension study. The study will consist of 2 open-label Phases: 4-week Induction phase (if applicable) and Open-Label Optimization/Maintenance phase (variable). Participants will enter the study Induction Phase from ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), ESKETINTRD3003 (NCT02493868), ESKETINTRD3005 (NCT02422186) and ESKETINTRD3006 (US sites only). Participants will enter the study Open-Label Optimization/Maintenance phase from ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), ESKETINTRD3003 (NCT02493868) (if appropriate at week 16) or ESKETINTRD3006 (US sites only). In the Open-Label Induction Phase, participants will self-administer flexibly-dosed intranasal esketamine. During first 4 weeks in Optimization/Maintenance Phase responder participants from the induction phase of study 54135419TRD3008, will continue on the same dose of intranasal esketamine from the induction phase and have a weekly intranasal treatment session frequency. Participants entering the optimization/maintenance phase from study ESKETINTRD3005 will also have a weekly intranasal treatment session frequency. However, as the ESKETINTRD3005 intranasal study medication is blinded at the time of entry into the current study, the dose of intranasal esketamine will be administered as outlined in protocol. Participants entering the optimization/maintenance phase from study ESKETINTRD3003 (Direct Entry) or ESKETINTRD3004 who were ongoing in the Optimization, Maintenance, or Optimization/Maintenance phase, respectively, will have the option to have their current intranasal dosing frequency adjusted at the time of entry into 54135419TRD3008 study and should remain on the selected frequency from week 1 to week 4. A one-time dose change will be permitted at study entry. After 4 weeks, intranasal esketamine treatment sessions will be individualized to either once weekly or once every other week at the fixed 2-week interval (based on clinical global impression - severity [CGI-S] performed at that visit), and every 4 weeks for subjects dosed at the 4 week interval. Participants safety will be monitored throughout the study.
- Based on the prior study the participant is entering 54135419TRD3008 from: a) From ESKETINTRD3001 (NCT02417064) or ESKETINTRD3002 (NCT02418585) study: Participant has completed the induction phase and the 2-weeks follow up phase visit; or Participants completed the induction phase and was a responder and study ESKETINTRD3003 is terminated.; b) From ESKETINTRD3003 (NCT02493868) study: (1) Participant relapsed during the maintenance phase; or (2) Participant was in the induction phase of the ESKETINTRD3003 study when the study was terminated and, after completion of the induction phase, was determined to be a responder; or (3) Participant was in the optimization or maintenance phases at the time the study was terminated; or (4) or (5) Participants was in the induction phase and after completion of induction phase was determined to not meet response criteria (1) Participant completed ESKETINTRD3004 study (optimization/maintenance phase); or (2) Participant was in the induction phase of the ESKETINTRD3004 study when the study was terminated and, after completion of the induction phase, was determined to be a responder; or (3) Participant was in the optimization/maintenance phase at the time the study was terminated; (4) Participant was in the induction phase and did not meet criteria for response may be eligible for to be rolled over into 54135419TRD3008. d) From ESKETINTRD3005 (NCT02422186) study: Participant was in the induction phase of the ESKETINTRD3005 study at the time enrollment into the ESKETINTRD3004 study was closed and, after completion of the induction phase, was determined to be a responder or did not meet the criteria for response. e) From ESKETINTRD3006 study (US Study sites only) (1) Participant completed the induction phase and was a responder.
- Participant must be medically stable on the basis of physical examination, vital signs, pulse oximetry, and 12-lead Electrocardiogram (ECG) performed predose on the day of the first intranasal treatment session. If there are any abnormalities that are not specified in the inclusion and exclusion criteria, their clinical significance must be determined by the investigator and recorded in the participant's source documents and initialed by the investigator
- Participant must be medically stable according to the investigator's judgment and knowledge of the subject's medical stability in the parent study. This determination must be documented.
- A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [b-hCG]) predose on the day of the first intranasal treatment session
- During the study (that is, from the first intranasal treatment session) and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of intranasal study medication, a man who is sexually active with a woman of childbearing potential must be practicing a highly effective method of contraception with his female partner c) must agree not to donate sperm.
- The evaluation of the benefit versus risk of continued intranasal esketamine treatment is not favorable for the participant in the opinion of the investigator
- Since the last study visit in the participant's prior study, participant has suicidal ideation with intent to act per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS) [corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) in the suicidal ideation module of the C-SSRS] or suicidal behavior per the investigator's clinical judgment or based on the C-SSRS (corresponding to any score higher than 0 in the suicidal behavior module of the C-SSRS)
- Participant has positive test result(s) for drugs of abuse (including barbiturates, methadone, opiates, cocaine, phencyclidine, and amphetamine/methamphetamine) predose on the day of the first intranasal treatment session
- Participant has any anatomical or medical condition that, per the investigator's clinical judgment based on assessment, may impede delivery or absorption of intranasal study drug
- Participant has taken any prohibited therapies that would not permit administration of the first intranasal treatment session