A Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02418585
• Date of registration: 13/04/2015
• Prospective Registration: Yes
• Primary sponsor: Janssen Research & Development, LLC
• Public title: A Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression TRANSFORM-2
• Scientific title: A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression
• Date of first enrolment: August 7, 2015
• Target sample size: 236
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02418585
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Brazil, Czech Republic, Czechia, Germany, Poland, Spain, United States

Contacts

• Name: Janssen Research & Development, LLC Clinical Trial
• Affiliation: Janssen Research & Development, LLC

Key inclusion & exclusion criteria

Inclusion Criteria:

- At the time of signing the informed consent form (ICF), participant must be a man or
woman 18 (or older if the minimum legal age of consent in the country in which the
study is taking place is greater than [>]18) to 64 years of age, inclusive

- At the start of the screening/prospective observational phase, participant must meet
the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria
for single-episode major depressive disorder (MDD) (if single-episode MDD, the
duration must be greater than or equal to [>=] 2 years) or recurrent MDD, without
psychotic features, based upon clinical assessment and confirmed by the
Mini-International Neuropsychiatric Interview (MINI)

- At the start of the screening/prospective observational phase, participant must have
an Inventory of Depressive Symptomatology-Clinician rated ( IDS-C30) total score of
greater than or equal to (>=) 34

- At the start of the screening/prospective observational phase, participant must have
had non-response (greater than or equal to [<=25] percent [%] improvement) to =1 but
less than or equal to (<=) 5 (if current episode is >2 years, upper limit is
applicable to only the last 2 years) oral antidepressant treatments in the current
episode of depression, assessed using the Massachusetts General Hospital -
Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and documented by medical
history and pharmacy/prescription records, for the current episode of depression. In
addition, the participant is taking a different oral antidepressant treatment (on the
MGH-ATRQ) for at least the previous 2 weeks at or above the minimum therapeutic dose

- The participant's current major depressive episode, depression symptom severity (Week
1 MADRS total score >=28 required), and antidepressant treatment response in the
current depressive episode, must be confirmed using a Site Independent Qualification
Assessment

Exclusion Criteria:

- Participants who have previously demonstrated nonresponse of depressive symptoms to
esketamine or ketamine in the current major depressive episode, to all 4 of the oral
antidepressant treatment options available for the double-blind induction phase (ie,
duloxetine, escitalopram, sertraline, and venlafaxine extended release [XR]) in the
current major depressive episode (based on MGH-ATRQ), or an adequate course of
treatment with electroconvulsive therapy (ECT) in the current major depressive
episode, defined as at least 7 treatments with unilateral/bilateral ECT

- Participant has received vagal nerve stimulation (VNS) or has received deep brain
stimulation (DBS) in the current episode of depression

- Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with
psychosis, bipolar or related disorders (confirmed by the MINI), comorbid obsessive
compulsive disorder, intellectual disability (DSM-5 diagnostic codes 317, 318.0,
318.1, 318.2, 315.8, and 319), borderline personality disorder, antisocial personality
disorder, histrionic personality disorder, or narcissistic personality disorder

- Participant has homicidal ideation/intent, per the investigator's clinical judgment,
or has suicidal ideation with some intent to act within 6 months prior to the start of
the screening/prospective observational phase, per the investigator's clinical
judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS)

- Participants with history of moderate or severe substance or alcohol use disorder
according to DSM-5 criteria



Age minimum: 18 Years
Age maximum: 64 Years
Gender: All

Health Condition(s) or Problem(s) studied

Treatment-resistant Depression

Intervention(s)

Drug: Duloxetine (Oral Antidepressant)

Drug: Placebo

Drug: Sertraline (Oral Antidepressant)

Drug: Escitalopram (Oral antidepressant)

Drug: Esketamine

Drug: Venlafaxine Extended Release (XR) (Oral Antidepressant)

Primary Outcome(s)

Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Day 28 in the Double-blind Induction Phase- Mixed-Effects Model Using Repeated Measures (MMRM) Analysis [Time Frame: Baseline up to Day 28 of Double-blind Induction Phase]

Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- Analysis of Covariance (ANCOVA) Analysis [Time Frame: Baseline up to Endpoint (Double-blind Induction Phase [Day 28])]

Secondary Outcome(s)

Percentage of Participants With Onset of Clinical Response on Day 2 and Day 8 [Time Frame: Day 2 up to Day 28 and Day 8 up to Day 28]

Change From Baseline in Sheehan Disability Scale (SDS) Total Score up to Day 28 of Double-blind Induction Phase- MMRM Analysis [Time Frame: Baseline up to Day 28 of Double-blind Induction phase]

Change From Baseline in Sheehan Disability Scale (SDS) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis [Time Frame: Baseline up to Endpoint (Double-blind Induction Phase [Day 28])]

Change From Baseline in EQ 5D-5L-Health Status Index to End of Double-blind Induction Phase (Day 28) [Time Frame: Baseline up to End of Double-blind Induction Phase (Day 28)]

Change From Baseline in Patient Health Questionnaire - 9-Item Depression Module (PHQ-9) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis [Time Frame: Baseline up to Endpoint (Double-blind Induction Phase [Day 28])]

Percentage of Participants in Remission (SDS Total Score <=6 and Individual Item Scores Each <=2) at the End of 4-Week Double-blind Induction Phase (Day 28) [Time Frame: At Day 28 (End of Double-blind Induction Phase)]

Change From Baseline in EQ 5D-5L- European Quality of Life - Visual Analogue Scale (EQ-VAS) to End of Double-blind Induction Phase (Day 28) [Time Frame: Baseline up to End of Double-blind Induction Phase (Day 28)]

Percentage of Participants in Remission (MADRS<=12) at the Endpoint (Double-blind Induction Phase [Day 28]) [Time Frame: At Endpoint (Double-blind Induction Phase [Day 28])]

Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score up to Endpoint (Double-blind Induction Phase [Day 28]) [Time Frame: Baseline up to Endpoint (Double-blind Induction Phase [Day 28])]

Change From Baseline in EQ 5D-5L- Sum Score to End of Double-blind Induction Phase (Day 28) [Time Frame: Baseline up to End of Double-blind Induction Phase (Day 28)]

Percentage of Participants in Response (SDS Total Score <=12 and Individual Item Scores Each <=4) at the End of 4-Week Double-blind Induction Phase (Day 28) [Time Frame: At Day 28 [end of Double-blind Induction Phase]]

Change From Baseline in Generalized Anxiety Disorder (GAD-7) Total Score up to Endpoint (Double-blind Induction Phase [Day 28]) [Time Frame: Baseline up to Endpoint (Double-blind Induction Phase [Day 28])]

Change From Baseline in Patient Health Questionnaire - 9-Item Depression Module (PHQ-9) Total Score up to Day 28 of Double-blind Induction Phase- MMRM Analysis [Time Frame: Baseline up to Day 28 of Double-blind Induction phase]

Percentage of Participants Who Achieved >=50% Reduction From Baseline in MADRS Total Score at the Endpoint (Double-blind Induction Phase [Day 28]) [Time Frame: At Endpoint (Double-blind Induction Phase [Day 28])]

Secondary ID(s)

ESKETINTRD3002

CR107147

2014-004585-22

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/04/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02418585