Clinical trial • Phase III • Psychiatry
ESKETAMINE for Major Depressive Disorder
Phase III trial of ESKETAMINE for Major Depressive Disorder.
Overview
- Trial Therapeutic Area
- Psychiatry
- Trial Disease
- Major Depressive Disorder
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 24-07-2025
- First CTIS Authorization Date
- 19-11-2025
Trial design
Randomised, oral midazolam comparator: midazolam-ratiopharm® 2 mg/ml oral solution (psychoactive placebo). dose presented in product data as mg/kg but specific mg/kg dose not stated in the ctis record. placebo arms include oral placebo and intranasal placebo. active arm: esketamine 84 mg intranasal (single first dose) in addition to comprehensive soc (ssri).-controlled Phase III trial across 27 sites in Italy, Romania, Hungary and others.
- Randomised
- Yes
- Comparator
- Oral midazolam comparator: Midazolam-ratiopharm® 2 mg/ml oral solution (psychoactive placebo). Dose presented in product data as mg/kg but specific mg/kg dose not stated in the CTIS record. Placebo arms include Oral placebo and Intranasal Placebo. Active arm: Esketamine 84 mg intranasal (single first dose) in addition to comprehensive SoC (SSRI).
- Target Sample Size
- 162
- Trial Duration For Participant
- 5
Eligibility
Recruits 162 paediatric patients.
- Vulnerable Population
- Adolescents (12 to <18 years) are included and flagged as a vulnerable population. The trial uses age-appropriate consent/assent processes: separate adolescent assent forms and parent/guardian informed consent forms and subject information sheets are provided (documents listed for Adolescent Assent and Parent/Guardian ICFs). Multiple language materials are provided for participating countries (examples in Italian, English, Spanish, Hungarian, Romanian).
Inclusion criteria
- {"criterion_text":"- 1. Adolescents: 12 to <18 years\n- 2. Meet DSM-5 diagnostic criteria for MDD, without psychotic features, based upon clinical assessment and MINI-KID (Sheehan 2010).\n- 3. CGI-SS-R score of “Markedly suicidal” or greater (ie, ≥4) at both screening and baseline (predose) visits.\n- 4. Acute psychiatric hospitalization is clinically warranted due to subject’s acute suicidality.\n- 5. CDRS-R total score ≥58 (moderate to severe depression) at baseline (predose).\n- 6. As part of SoC treatment, the participant must agree to: a. be hospitalized voluntarily for a recommended period of 5 days (4 nights) from Day 1, Randomization Day b. take 1 of the following prescribed SoC SSRI antidepressants, as approved and available in the participating country/territory: fluoxetine, escitalopram, or sertraline at least during the DB treatment phase.\n- 7. Medically stable"}
Exclusion criteria
- {"criterion_text":"- 1. Current DSM-5 diagnosis of bipolar (or related disorders), intellectual disability, autism spectrum disorder, conduct disorder, oppositional defiant disorder, borderline personality disorder.\n- 2. Current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychosis.\n- 3. History of moderate or severe Substance or Alcohol Use Disorder\n- 4. Participant has received prior (lifetime) treatment with (es) ketamine (other than for anesthetic purposes).\n- 5. Body weight of <40 kg at screening visit."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Change from baseline (Day 1, predose) at 24 hours post first dose in depressive symptoms, as measured by the CDRS-R total score","definition_or_measurement_approach":"Change from baseline (Day 1, predose) measured by the CDRS-R (Children's Depression Rating Scale - Revised) total score at 24 hours after the first dose"}
Recruitment
- Planned Sample Size
- 162
- Recruitment Window Months
- 66
- Consent Approach
- Informed consent includes separate materials for adolescent assent and parent/guardian consent (SIS and ICF Adolescent, SIS and ICF Parent Guardian). Additional ICFs available for clinical, withdrawal, privacy and pregnant partner contexts. Documents are available in country/language-specific versions (Italian, English, Spanish, Hungarian, Romanian as indicated by file naming). Consent by parent/guardian required for minors; adolescent assent obtained using age-appropriate forms.
Methods
- Country-specific recruitment materials and arrangements documented (recruitment brochures, assent tools, flip charts and ICF materials). Materials are provided for Italy, Romania, Hungary and Spain (K1/K2 recruitment documents listed). Target audience: adolescents 12 to <18 years with major depressive disorder and acute suicidal ideation/behavior; channels and specific outreach methods not specified in the CTIS JSON.
- Use of patient organisations at site level (example: patient organisation listed as a site in Spain) and local site recruitment practices (details not specified).
Geography
- Total Number Of Sites
- 27
- Total Number Of Participants
- 96
Italy
- Earliest CTIS Part Ii Submission Date
- 13-10-2025
- Latest Decision Or Authorization Date
- 19-11-2025
- Processing Time Days
- 37
- Number Of Sites
- 9
- Number Of Participants
- 30
Sites
- Site Name
- Azienda Sanitaria Dell'Alto Adige
- Department Name
- U.O.C. Neuropsichiatria dell'lnfanzia e dell'Adolescenza
- Principal Investigator Name
- Marco Lamberti
- Principal Investigator Email
- marco.lamberti@sabes.it
- Contact Person Name
- Marco Lamberti
- Contact Person Email
- marco.lamberti@sabes.it
- Site Name
- Azienda Sanitaria Provinciale Di Catania
- Department Name
- U.O.C. Neuropsichiatria dell'lnfanzia e dell' Adolescenza
- Principal Investigator Name
- Maria Stissi
- Principal Investigator Email
- maria.stissi@aspct.it
- Contact Person Name
- Maria Stissi
- Contact Person Email
- maria.stissi@aspct.it
- Site Name
- Azienda Ospedaliera Universitaria Meyer IRCCS
- Department Name
- AOU Meyer-Dipartimento di Neurologia Pediatrica
- Principal Investigator Name
- Tiziana Pisano
- Principal Investigator Email
- tiziana.pisano@meyer.it
- Contact Person Name
- Tiziana Pisano
- Contact Person Email
- tiziana.pisano@meyer.it
- Site Name
- IRCCS Istituto Giannina Gaslini
- Department Name
- U.O.C. Neuropsichiatria Infantile
- Principal Investigator Name
- Lino Nobili
- Principal Investigator Email
- linonobili@gaslini.org
- Contact Person Name
- Lino Nobili
- Contact Person Email
- linonobili@gaslini.org
- Site Name
- Azienda Ospedaliero Universitaria Ospedali Riuniti
- Department Name
- S.C. di Neuropsichiatria Infantile
- Principal Investigator Name
- Giusy Pustorino
- Principal Investigator Email
- giusypusto@gmail.com
- Contact Person Name
- Giusy Pustorino
- Contact Person Email
- giusypusto@gmail.com
- Site Name
- ARNAS G. Brotzu
- Department Name
- Neuropsichiatria dell'Infanzia e Adolescenza
- Principal Investigator Name
- Sara Carucci
- Principal Investigator Email
- sara.carucci@gmail.com
- Contact Person Name
- Sara Carucci
- Contact Person Email
- sara.carucci@gmail.com
- Site Name
- Azienda Ospedaliera Universitaria Federico II Di Napoli
- Department Name
- Neuropsichiatria Infantile
- Principal Investigator Name
- Maria Pia Riccio
- Principal Investigator Email
- piariccio@gmail.com
- Contact Person Name
- Maria Pia Riccio
- Contact Person Email
- piariccio@gmail.com
- Site Name
- Azienda Ospedaliero Universitaria Di Sassari
- Department Name
- U.O. Neuropsichiatria Infantile
- Principal Investigator Name
- Stefano Sotgiu
- Principal Investigator Email
- stefanos@uniss.it
- Contact Person Name
- Stefano Sotgiu
- Contact Person Email
- stefanos@uniss.it
- Site Name
- Azienda Ospedaliero Universitaria Di Sassari (duplicate listed?)
Romania
- Earliest CTIS Part Ii Submission Date
- 07-11-2025
- Latest Decision Or Authorization Date
- 24-11-2025
- Processing Time Days
- 17
- Number Of Sites
- 4
- Number Of Participants
- 16
Sites
- Site Name
- Spitalul Clinic De Psihiatrie Dr. Gheorghe Preda Sibiu
- Department Name
- Pediatric Psychiatry
- Principal Investigator Name
- Ciprian Bacila
- Principal Investigator Email
- office@medicina-psihiatrie.ro
- Contact Person Name
- Ciprian Bacila
- Contact Person Email
- office@medicina-psihiatrie.ro
- Site Name
- Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
- Department Name
- Pediatric Psychiatry
- Principal Investigator Name
- Florina Rad
- Principal Investigator Email
- secretariat@spital-obregia.ro
- Contact Person Name
- Florina Rad
- Contact Person Email
- secretariat@spital-obregia.ro
- Site Name
- Spitalul Clinic De Urgenta Pentru Copii Cluj-Napoca
- Department Name
- Pediatric Psychiatry
- Principal Investigator Name
- Elena Predescu
- Principal Investigator Email
- psihiatrie@spitcocluj.ro
- Contact Person Name
- Elena Predescu
- Contact Person Email
- psihiatrie@spitcocluj.ro
- Site Name
- Spitalul Clinic De Urgenta Pentru Copii Louis Turcanu Timisoara
- Department Name
- Pediatric Psychiatry
- Principal Investigator Name
- Laura Nussbaum
- Principal Investigator Email
- nussbaumlaura@yahoo.com
- Contact Person Name
- Laura Nussbaum
- Contact Person Email
- nussbaumlaura@yahoo.com
Hungary
- Earliest CTIS Part Ii Submission Date
- 19-09-2025
- Latest Decision Or Authorization Date
- 09-02-2026
- Processing Time Days
- 143
- Number Of Sites
- 4
- Number Of Participants
- 16
Sites
- Site Name
- University Of Debrecen
- Department Name
- Gyermek- es Ifjusagpszichiatriai Osztaly
- Principal Investigator Name
- Eniko Bugan
- Principal Investigator Email
- dr.bugan.eniko@med.unideb.hu
- Contact Person Name
- Eniko Bugan
- Contact Person Email
- dr.bugan.eniko@med.unideb.hu
- Site Name
- Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz
- Department Name
- Pszichiatriai, Mentalhigienes és Addiktologiai Osztaly
- Principal Investigator Name
- Gabor Feller
- Principal Investigator Email
- fellerg@petz.gyor.hu
- Contact Person Name
- Gabor Feller
- Contact Person Email
- fellerg@petz.gyor.hu
- Site Name
- University Of Szeged
- Department Name
- Gyermek- es Ifjusagpszichiatria Osztaly
- Principal Investigator Name
- Krisztina Kapornai
- Principal Investigator Email
- kapornai.krisztina@szte.hu
- Contact Person Name
- Krisztina Kapornai
- Contact Person Email
- kapornai.krisztina@szte.hu
- Site Name
- Vadaskert Alapitvany A Gyermekek Lelki Egeszsegeert
- Principal Investigator Name
- Cristian Puskas
- Principal Investigator Email
- dr.pcristian@gmail.com
- Contact Person Name
- Cristian Puskas
- Contact Person Email
- dr.pcristian@gmail.com
Spain
- Earliest CTIS Part Ii Submission Date
- 17-10-2025
- Latest Decision Or Authorization Date
- 14-05-2026
- Processing Time Days
- 209
- Number Of Sites
- 10
- Number Of Participants
- 34
Sites
- Site Name
- Hospital Universitario La Paz
- Department Name
- PSIQUIATRIA
- Principal Investigator Name
- CARMEN MORENO RUIZ
- Principal Investigator Email
- cmoreno@hggm.es
- Contact Person Name
- CARMEN MORENO RUIZ
- Contact Person Email
- cmoreno@hggm.es
- Site Name
- Hospital Universitario Marques De Valdecilla
- Department Name
- PSIQUIATRIA
- Principal Investigator Name
- BEATRIZ PAYA GONZALEZ
- Principal Investigator Email
- mbeatriz.paya@scsalud.es
- Contact Person Name
- BEATRIZ PAYA GONZALEZ
- Contact Person Email
- mbeatriz.paya@scsalud.es
- Site Name
- Clinica Universidad De Navarra
- Department Name
- PSIQUIATRIA
- Principal Investigator Name
- MARIA VALLEJO VALDIVIESO
- Principal Investigator Email
- mvvaldiviel@unav.es
- Contact Person Name
- MARIA VALLEJO VALDIVIESO
- Contact Person Email
- mvvaldiviel@unav.es
- Site Name
- Parc Tauli Hospital Universitari
- Department Name
- PSIQUIATRIA
- Principal Investigator Name
- MONTSERRAT DOLZ ABADIA
- Principal Investigator Email
- montserrat.dolz@sjd.es
- Contact Person Name
- MONTSERRAT DOLZ ABADIA
- Contact Person Email
- montserrat.dolz@sjd.es
- Site Name
- Hospital Universitario Central De Asturias
- Department Name
- PSIQUIATRIA
- Principal Investigator Name
- ELISA SEIJO ZAZO
- Principal Investigator Email
- eseijo@yahoo.es
- Contact Person Name
- ELISA SEIJO ZAZO
- Contact Person Email
- eseijo@yahoo.es
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- PSIQUIATRIA
- Principal Investigator Name
- MARIA JOSE PARELLADA REDONDO
- Principal Investigator Email
- parelladahggm@gmail.com
- Contact Person Name
- MARIA JOSE PARELLADA REDONDO
- Contact Person Email
- parelladahggm@gmail.com
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- PSIQUIATRIA
- Principal Investigator Name
- ANA ORTIZ GARCIA
- Principal Investigator Email
- AEORTIZ@clinic.cat
- Contact Person Name
- ANA ORTIZ GARCIA
- Contact Person Email
- AEORTIZ@clinic.cat
- Site Name
- Althaia Xarxa Assistencial Universitaria De Manresa Fundacio Privada
- Department Name
- PSIQUIATRIA
- Principal Investigator Name
- AUREA AUTET PUIG
- Principal Investigator Email
- aautet@althaia.cat
- Contact Person Name
- AUREA AUTET PUIG
- Contact Person Email
- aautet@althaia.cat
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- PSIQUIATRIA
- Principal Investigator Name
- JOSEP ANTONI RAMOS QUIROGA
- Principal Investigator Email
- antoni.ramos@vallhebron.cat
- Contact Person Name
- JOSEP ANTONI RAMOS QUIROGA
- Contact Person Email
- antoni.ramos@vallhebron.cat
- Site Name
- Hospital Sant Joan De Deu Barcelona
- Department Name
- PSIQUIATRIA
- Principal Investigator Name
- MONTSERRAT DOLZ ABADIA
- Principal Investigator Email
- montserrat.dolz@sjd.es
- Contact Person Name
- MONTSERRAT DOLZ ABADIA
- Contact Person Email
- montserrat.dolz@sjd.es
Sponsor
Primary sponsor
- Full Name
- Janssen Cilag International
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Belgium
Contract research organisations
- Name
- Iqvia Biotech LLC
- Responsibilities
- Operational/CRO responsibilities (sponsorDuties code: 13); contact michael.terwilliger@iqvia.com
- Name
- 4g Clinical LLC
- Responsibilities
- Operational/CRO responsibilities (sponsorDuties codes: 14,3); contact info@4gclinical.com
Third parties
- {"country":"United States","full_name":"Iqvia Biotech LLC","duties_or_roles":"sponsorDuties codes: 13","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"eCOA device (Rater Station); sponsorDuties codes: 15, 6, 7","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties codes: 14, 3","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Australia","full_name":"Cogstate Limited","duties_or_roles":"Digital cognitive testing; sponsorDuties codes: 15, 6, 7","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Ancillare LP","duties_or_roles":"Ancillary Supplies; sponsorDuties code: 15","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Central laboratory services; sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG device, ECG report and central ECG report reveiw; sponsorDuties code: 15","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Spravato 28 mg nasal spray, solution
- Active Substance
- ESKETAMINE
- Modality
- Small molecule
- Routes Of Administration
- Nasal (intranasal)
- Route
- Intranasal
- Authorisation Status
- Marketing authorisation present (marketingAuthNumber EU/1/19/1410/001, prodAuthStatus 2)
- Starting Dose
- 84 mg (single first dose as stated in main objective)
- Dose Levels
- Single dose (84 mg) as per objective; no multiple/escalation levels stated
- Frequency
- Single (first) dose
- Maximum Dose
- 84 mg (not otherwise specified)
- Investigational Product Name
- Midazolam-ratiopharm® 2 mg/ml orale Lösung
- Active Substance
- MIDAZOLAM
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Marketing authorisation present (prodAuthStatus 2)
- Investigational Product Name
- Oral placebo
- Modality
- Other
- Investigational Product Name
- Intranasal Placebo
- Modality
- Other
- Routes Of Administration
- Intranasal
- Route
- Intranasal
- Combination Treatment
- Yes
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