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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02422186
• Date of registration: 16/04/2015
• Prospective Registration: Yes
• Primary sponsor: Janssen Research & Development, LLC
• Public title: A Study to Evaluate the Efficacy, Safety, and Tolerability of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Participants With Treatment-resistant Depression TRANSFORM-3
• Scientific title: A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Subjects With Treatment-resistant Depression
• Date of first enrolment: August 20, 2015
• Target sample size: 139
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02422186
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Brazil, Bulgaria, Finland, France, Korea, Republic of, Lithuania, Poland, South Africa, Spain, Sweden, United Kingdom, 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 65 years of age or older

- 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 (>=) 31

- At the start of the Screening/Prospective observational Phase, participants must have
had nonresponse (less than or equal to 25% improvement) to >=1 but less than or equal
to (<=) 8 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 records by medical and
pharmacy/prescription records, or a letter from the treating physician, for the
current episode of depression

- Participant must be taking one of the oral antidepressant treatment with nonresponse
that is documented on the MGH-ATRQ at the start of the screening/prospective
observational phase

- The participant's current major depressive episode, depression symptom severity (Week
1 MADRS total score greater than or equal to 24 required) and treatment response to
antidepressant treatments used in the current depressive episode (retrospectively
assessed) must be confirmed for participation in a clinical study based on a
Site-Independent Qualification Assessment

- Participant must be medically stable on the basis of clinical laboratory tests
performed in the screening/prospective observational phase

Exclusion Criteria:

- The participant's depressive symptoms have previously demonstrated nonresponse to:
Esketamine or ketamine in the current major depressive episode per clinical judgment,
or all of the 4 oral antidepressant treatment options available for the double-blind
induction Phase (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 ECT

- Participants who has received vagal nerve stimulation (VNS) or who 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), obsessive compulsive
disorder (current episode only), intellectual disability ( 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) and also
includes history of suicidal behavior within the past year prior to start of the
screening/prospective observational phase

- Participant has a history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid
diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related
use disorder
- Participant has a Mini Mental State Examination (MMSE) < 25 or <22 for those
participants with less than an equivalent of high school education

- Participant has neurodegenerative disorder (eg, Alzheimer's Disease, Vascular
dementia, Parkinson's disease with clinical evidence of cognitive impairment) or
evidence of mild cognitive impairment (MCI)

- Participant has a history of uncontrolled hypertension; current or past history of
significant pulmonary insufficiency/condition;clinically significant ECG
abnormalities; current or past history of seizures; clinically significant
cardiovascular disorders including cerebral and cardiac vascular disease



Age minimum: 65 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Depressive Disorder, Treatment-Resistant

Intervention(s)

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

Drug: Duloxetine (Oral Antidepressant)

Drug: Esketamine

Drug: Escitalopram (Oral Antidepressant)

Drug: Sertraline (Oral Antidepressant)

Drug: Placebo

Primary Outcome(s)

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

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

Secondary Outcome(s)

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

Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) to Endpoint (Double-blind Induction Phase [Day 28]): EQ-VAS [Time Frame: Baseline and Endpoint (Double-blind Induction Phase [Day 28])]

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

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

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

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

Secondary ID(s)

ESKETINTRD3005

2014-004588-19

CR107129

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 24/04/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02422186