A Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed 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: NCT02417064
• Date of registration: 10/04/2015
• Prospective Registration: Yes
• Primary sponsor: Janssen Research & Development, LLC
• Public title: A Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression TRANSFORM-1
• Scientific title: A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression
• Date of first enrolment: August 10, 2015
• Target sample size: 346
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02417064
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Belgium, Brazil, Canada, Estonia, France, Hungary, Japan, Mexico, Poland, Slovakia, 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, participants must have
had non-response (less 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 taken at adequate
dosage and for adequate duration, as 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.

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 (i.e,
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
psychotic features bipolar or related disorders (confirmed by the MINI), obsessive
compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes
317, 318.0, 318.1, 318.2, 315.8, and 319), autism spectrum disorder, 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: Esketamine

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

Drug: Duloxetine (Oral Antidepressant)

Drug: Placebo

Drug: Sertraline (Oral Antidepressant)

Drug: Escitalopram (Oral antidepressant)

Primary Outcome(s)

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

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

Secondary Outcome(s)

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

Change From Baseline in Patient Health Questionnaire-9 (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 in Remission (MADRS<=12) at the Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis (LOCF Data) [Time Frame: At Day 28 (Double-blind Endpoint)]

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

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

Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) up to End of Double-blind Induction Phase (Day 28): EQ-VAS [Time Frame: Baseline up to end of Double-blind induction phase (Day 28)]

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

Percentage of Participants With Onset of Clinical Response by 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 Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis [Time Frame: Baseline up to Double-blind Endpoint (Day 28)]

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

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

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

Percentage of Participants Who Achieved at Least 50% Reduction From Baseline in MADRS Total Score at Day 28 of Double-blind Induction Phase (Observed Data) [Time Frame: At Day 28 of Double-blind Induction phase]

Secondary ID(s)

2014-004584-20

ESKETINTRD3001

CR107146

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/04/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02417064