Clinical trial NCT02782104: A Long-term Safety Study of Esketamine Nasal Spray in Treatment-resistant Depression
Official title: An Open-label Long-term Extension Safety Study of Esketamine Nasal Spray in Treatment-resistant Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depressive Disorder, Treatment-Resistant
Keywords: Depressive Disorder, Treatment-Resistant
Esketamine
JNJ-54135419
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-05-25
Enrollment: 1148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and tolerability of esketamine nasal spray in participants with treatment-resistant depression (TRD).

Detailed description: 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 esketamine nasal spray. During first 4 weeks in Optimization/Maintenance Phase responder participants from the induction phase of study 54135419TRD3008, will continue on the same dose of esketamine nasal spray 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 esketamine nasal spray 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, esketamine nasal spray 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 participants dosed at the 4 week interval. Participants safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* The evaluation of the benefit versus risk of continued esketamine nasal spray 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

Primary outcomes:
measure: Change From Study Baseline in Computerized Cognitive Battery Domain Score: Detection Test (DET) Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Study Baseline in Computerized Cognitive Battery Domain Score: Identification Test (IDN) Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Card Learning Test (OCL) Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Back Test (ONB) Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Study Baseline in Computerized Cognitive Battery Domain Score: Groton Maze Learning Test (GMLT) Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: IND Phase: up to 4 weeks; OP/MA Phase: up to 78 months
measure: Change From Baseline in Heart Rate
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Baseline in Systolic and Diastolic Blood Pressure
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Baseline in Respiratory Rate
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Baseline in Blood Oxygen Saturation
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Secondary outcomes:
measure: Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Baseline in Participant-Reported Depressive Symptoms Using the Patient Health Questionnaire - 9 (PHQ-9) Total Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Baseline in Clinical Global Impression-severity (CGI-S) Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Baseline in Sheehan Disability Scale (SDS) Total Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Baseline in Participant-Reported Health-related Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Valuation Index Score (VAS)
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Baseline as Assessed by EQ 5D-5L: Sum Score
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
measure: Change From Baseline in Participant- Reported Health Related Quality of Life Using the Quality of Life in Depression Scale (QLDS)
timeFrame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Little Rock
country: United States
state: Arkansas
city: Garden Grove
country: United States
state: California
city: Glendale
country: United States
state: California
city: Oakland
country: United States
state: California
city: Orange
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Rafael
country: United States
state: California
city: Hartford
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Gainesville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Hoffman Estates
country: United States
state: Illinois
city: Joliet
country: United States
state: Illinois
city: Maywood
country: United States
state: Illinois
city: Skokie
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Wichita
country: United States
state: Kansas
city: Lake Charles
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Gaithersburg
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: New Bedford
country: United States
state: Massachusetts
city: Watertown
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Rochester Hills
country: United States
state: Michigan
city: O'Fallon
country: United States
state: Missouri
city: Saint Charles
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Cedarhurst
country: United States
state: New York
city: New York
country: United States
state: New York
city: Staten Island
country: United States
state: New York
city: Hickory
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Allentown
country: United States
state: Pennsylvania
city: Media
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Lincoln
country: United States
state: Rhode Island
city: Providence
country: United States
state: Rhode Island
city: Charleston
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Wichita Falls
country: United States
state: Texas
city: Charlottesville
country: United States
state: Virginia
city: Waukesha
country: United States
state: Wisconsin
city: Banfield
country: Argentina
city: Ciudad Autonoma de Buenos Aires
country: Argentina
city: Ciudad Autónoma De Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: La Plata
country: Argentina
city: Mendoza
country: Argentina
city: Rosario
country: Argentina
city: Caulfield
country: Australia
city: Elizabeth Vale
country: Australia
city: Frankston
country: Australia
city: Vienna
country: Austria
city: Aalst
country: Belgium
city: Brugge
country: Belgium
city: Brussel
country: Belgium
city: Heusden-Zolder
country: Belgium
city: Liège
country: Belgium
city: Yvoir
country: Belgium
city: Belo Horizonte
country: Brazil
city: Curitiba
country: Brazil
city: Fortaleza
country: Brazil
city: Passo Fundo
country: Brazil
city: Porto Alegre
country: Brazil
city: Recife
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Sao Bernardo do Campo
country: Brazil
city: Sao Paulo
country: Brazil
city: Bourgas
country: Bulgaria
city: Kardzhali
country: Bulgaria
city: Pazardzhik
country: Bulgaria
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Rousse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Vancouver
country: Canada
state: British Columbia
city: Kingston
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Brno
country: Czechia
city: Plzen
country: Czechia
city: Prague
country: Czechia
city: Praha 10
country: Czechia
city: Praha 2
country: Czechia
city: Praha 6
country: Czechia
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Kuopio
country: Finland
city: Clermont-Ferrand Cedex 1
country: France
city: Douai
country: France
city: Nantes
country: France
city: Nîmes
country: France
city: Paris
country: France
city: Poitiers Cedex
country: France
city: Toulon Cedex
country: France
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Mainz
country: Germany
city: Mittweida
country: Germany
city: Oranienburg
country: Germany
city: Pfaffenhofen
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Gyor
country: Hungary
city: Pecs
country: Hungary
city: Sopron
country: Hungary
city: Szekszárd
country: Hungary
city: Vác
country: Hungary
city: Gwangju
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Kaunas
country: Lithuania
city: Kuala Lumpur
country: Malaysia
city: Guadalajara
country: Mexico
city: Leon
country: Mexico
city: Mexico City
country: Mexico
city: Mexico
country: Mexico
city: Monterrey
country: Mexico
city: San Luis Potosi
country: Mexico
city: Belchatow
country: Poland
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Gdansk
country: Poland
city: Leszno
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Bratislava
country: Slovakia
city: Liptovsky Mikulas
country: Slovakia
city: Rimavska Sobota
country: Slovakia
city: Roznava
country: Slovakia
city: Svidnik
country: Slovakia
city: Cape Town
country: South Africa
city: Pretoria
country: South Africa
city: Welgemoed
country: South Africa
city: Alcorcón
country: Spain
city: Barcelona
country: Spain
city: Bilbao
country: Spain
city: Madrid
country: Spain
city: Oviedo
country: Spain
city: Palma
country: Spain
city: Pamplona
country: Spain
city: Sabadell
country: Spain
city: Salamanca
country: Spain
city: Sant Boi de Llobregat
country: Spain
city: Torrevieja
country: Spain
city: Vitoria-Gasteiz
country: Spain
city: Zamora
country: Spain
city: Halmstad
country: Sweden
city: Lund
country: Sweden
city: Skövde
country: Sweden
city: Stockholm
country: Sweden
city: Kaohsiung
country: Taiwan
city: New Taipei
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Adana
country: Turkey
city: Ankara
country: Turkey
city: Bursa
country: Turkey
city: Istanbul
country: Turkey
city: Kucukcekmece/Istanbul
country: Turkey
city: Oanakkale
country: Turkey
city: Samsun
country: Turkey
city: Chesterfield
country: United Kingdom
city: Derby
country: United Kingdom
city: London
country: United Kingdom
city: Northampton
country: United Kingdom
city: Oxford
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Starr 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.