A Long-term Safety Study of Esketamine Nasal Spray in Treatment-resistant Depression

Study at a glance

From the registry record, last updated by the sponsor on 29 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

An Open-label Long-term Extension Safety Study of Esketamine Nasal Spray in Treatment-resistant Depression

ClinicalTrials.gov ID

NCT02782104

Acronym / sponsor ID

SUSTAIN-3 / CR108149

Conditions

Depressive Disorder, Treatment-Resistant

Keywords

Depressive Disorder, Treatment-Resistant, Esketamine, JNJ-54135419

Phase

Phase 3

Study type

Interventional

Recruitment status

Completed

Enrolment

1,148 participants (actual)

Lead sponsor

Janssen Research & Development, LLCIndustry (pharma, biotech, devices)

Study start

9 Jun 2016 (actual)

Primary completion

30 Dec 2022 (actual)

Study completion

30 Dec 2022 (actual)

First posted

25 May 2016 (estimated)

Results

Posted 20 Feb 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Not applicable

Intervention model

Single group

Masking

None (open label)

Number of arms

1

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Change From Study Baseline in Computerized Cognitive Battery Domain Score: Detection Test (DET) Score

   Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

   This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. The DET is a measure of psychomotor function and uses a well-validated simple reaction time. In this outcome measure, speed of performance of subjects (calculated as mean of the logarithmic base 10 transformed reaction times) for correct responses was reported. Total score ranged from 2 to 3.3 log 10 milliseconds (msec). Lower score indicated better performance. Higher change from baseline indicated better performance.

2. Change From Study Baseline in Computerized Cognitive Battery Domain Score: Identification Test (IDN) Score

   Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

   This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. IDN test is a measure of visual attention (choice reaction time) and scored for speed of response (mean of the log10 transformed reaction times for correct responses). Total score ranged from 2 to 3.3 log 10 msec. Lower score indicated better performance. Higher change from baseline indicated better performance.

3. Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Card Learning Test (OCL) Score

   Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

   This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. OCL test is a measure of visual episodic memory and visual recall test scored using arcsine transformation of the percentage of correct responses (CR). The range for OCL is 0 to 100 percent (%) accuracy; presented as an arcsin transformation, the range is 0 to 1.57. Higher score indicated better performance. Higher change from baseline indicated better performance.

4. Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Back Test (ONB) Score

   Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

   The ONB is a measure of working memory and scored for speed of correct response (mean of the log10-transformed reaction times for correct responses). Total score ranged from 2 to 3.54 log10 msec. Lower score indicated better performance. Higher change from baseline indicated better performance.

5. Change From Study Baseline in Computerized Cognitive Battery Domain Score: Groton Maze Learning Test (GMLT) Score

   Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

   This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. GMLT measures executive function; maze/sequencing test, scored for total number of errors. Total score ranged from 0 to 999 number of errors. Lower score indicated better performance. Higher change from baseline indicated better performance.

6. Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score

   Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

   The HVLT-R measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0-12); the total number of true-positive errors (0-12); and the range of recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher total recall score indicated higher cognition. The range of the recognition discrimination index is -12 to 12. Higher score indicated better performance and higher change from baseline indicated better performance.

7. Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score

   Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

   C-SSRS: interview-based instrument to systematically assess suicidal ideation (SI) and behavior, to assess whether participant experienced any of following: completed suicide, suicide attempt (response of "yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior ("yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active SI with methods without intent to act or some intent to act, without or with specific plan and intent), any self-injurious behavior with no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). Here, percentage of participants with >=1 positive behavior, participants with >=1 positive ideations; no event were reported.

8. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

   Time frame: IND Phase: up to 4 weeks; OP/MA Phase: up to 78 months

   An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Any AE occurring at or after the initial administration of study intervention up to end of study was considered as treatment-emergent.

9. Change From Baseline in Heart Rate

   Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

   Change from baseline (predose) in heart rate were reported.

10. Change From Baseline in Systolic and Diastolic Blood Pressure

    Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

    Change from baseline in systolic and diastolic blood pressure were reported.

11. Change From Baseline in Respiratory Rate

    Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

    Change from baseline in respiratory rate were reported.

12. Change From Baseline in Blood Oxygen Saturation

    Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months

    Change from baseline in blood oxygen saturation (predose) were reported.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2025.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 40319349Zaki N, Chen LN, Lane R, Doherty T, Drevets WC, Morrison RL, Sanacora G, Wilkinson ST, Young AH, Lacerda ALT, Paik JW, Popova V, Fu DJ. Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study. Int J Neuropsychopharmacol. 2025 Jun 6;28(6):pyaf027. doi: 10.1093/ijnp/pyaf027.
• Derived from this study: PubMed 39428602Vekhova KA, Namiot ED, Jonsson J, Schioth HB. Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations. Clin Pharmacol Ther. 2025 Feb;117(2):374-386. doi: 10.1002/cpt.3478. Epub 2024 Oct 20.
• Derived from this study: PubMed 37558912Castro M, Wilkinson ST, Al Jurdi RK, Petrillo MP, Zaki N, Borentain S, Fu DJ, Turkoz I, Sun L, Brown B, Cabrera P. Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study. CNS Drugs. 2023 Aug;37(8):715-723. doi: 10.1007/s40263-023-01026-3. Epub 2023 Aug 9.
• Derived from this study: PubMed 37173512Zaki N, Chen LN, Lane R, Doherty T, Drevets WC, Morrison RL, Sanacora G, Wilkinson ST, Popova V, Fu DJ. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study. Neuropsychopharmacology. 2023 Jul;48(8):1225-1233. doi: 10.1038/s41386-023-01577-5. Epub 2023 May 12.
• Derived from this study: PubMed 32818917Starr HL, Abell J, Larish A, Lewis S, DeMuro C, Gogate J, Jamieson C, Daly E, Zaki N, Kramer M. Self-reported review of the value of esketamine in patients with treatment-resistant depression: Understanding the patient experience in the STRIVE Study. Psychiatry Res. 2020 Nov;293:113376. doi: 10.1016/j.psychres.2020.113376. Epub 2020 Aug 8.

Related trials for Depressive Disorder, Treatment-Resistant

• RecruitingPhase 4

  Biomarker-Guided Antidepressant Selection

  Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)

• RecruitingPhase 2

  ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response

  Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant

• Active, not recruiting

  CET- REM (Correlating ECT Response to EEG Markers)

  ECT, Treatment Resistant Depression

• Active, not recruiting

  rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression

  Depression, Treatment Resistant

• Recruiting

  A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression

  Treatment Resistant Depression

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

173 sites in 26 countries: see every site and its status.