Clinical trial NCT02918318: A Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Doses of Intranasal Esketamine in Japanese Participants With Treatment Resistant Depression
Official title: A Randomized, Double-blind, Multicenter, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Doses of Intranasal Esketamine in Japanese Subjects With Treatment Resistant Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depression
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2016-09-28
Enrollment: 202
Sex: ALL
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of fixed dosed intranasal esketamine compared to intranasal placebo, as an add-on to an oral antidepressant in Japanese participants with treatment-resistant depression (TRD), in improving depressive symptoms.


Eligibility criteria: Inclusion Criteria:

* At the start of the screening phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) or recurrent major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (MINI). In the case of single-episode MDD, the participant must be diagnosed with persistent depressive disorder, which meets criteria of major depressive episode for a continuous duration of greater than or equal to (\>=)2 years, and the same physician from the site must be examining the participant for \>=2 years continuously as a primary care physician of the participant
* The participant's current major depressive episode, depression symptom severity (MADRS total score greater than or equal to \[\>=\] 28 required), and antidepressant treatment response in the current depressive episode, must be confirmed using the SAFER interview
* Participant must be medically stable on the basis of clinical laboratory tests, physical examination, medical history, vital signs (including blood pressure), pulse oximetry, and 12-lead electrocardiogram (ECG) performed in the screening phase
* A woman of childbearing potential must have a negative highly sensitive serum Beta (β) human chorionic gonadotropin \[β-hCG\] test at the start of the screening phase and a negative urine pregnancy test must be obtained before the first dose of study drug on Day 1 of the double-blind induction phase prior to randomization
* Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies

Exclusion Criteria:

* Participant has received vagal nerve stimulation or has received deep brain stimulation in the current episode of depression
* Participant previously received esketamine or ketamine as treatment for their MDD
* 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 phase
* Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 6 months before the start of the screening phase
* Participant has a current or past history of seizure disorder (uncomplicated childhood febrile seizures with no sequelae are not exclusionary)

Primary outcomes:
measure: Double-Blind (DB) Induction Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Day 28
timeFrame: Baseline (Day 1) up to Day 28 (DB phase) induction
Secondary outcomes:
measure: DB Induction Phase: Percentage of Participants With Response Based on MADRS Total Score
timeFrame: Days 2, 8, 15, 22 and 28 (DB induction phase)
measure: DB Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score
timeFrame: Days 2, 8, 15, 22 and 28 (DB induction phase)
measure: DB Induction Phase: Percentage of Participants Showing Onset of Clinical Response
timeFrame: Day 2 up to Day 28 (DB induction phase)
measure: DB Induction Phase: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Total Score up to Day 28
timeFrame: Baseline (Day 1) up to Day 28 (DB induction pahse)
measure: DB Induction Phase: Change From Baseline in Generalized Anxiety Disorder 7-Item Scale (GAD-7) up to Day 28
timeFrame: Baseline (Day 1) up to Day 28 (DB induction phase)
measure: DB Induction Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score up to Day 28
timeFrame: Baseline (Day 1) to Day 28 (DB induction phase)
measure: Posttreatment Phase: Time to Relapse in Participants With Remission (MADRS Total Score <=12)
timeFrame: From EndPoint (last post baseline assessment value during the DB induction phase [up to Day 28]) up to 24 weeks (posttreatment phase)
measure: Posttreatment Phase: Time to Relapse in Participants With Response (>=50% Reduction From Baseline in MADRS Total Score) But Who Are Not in Remission
timeFrame: From EndPoint (last post baseline assessment value during the DB induction phase [up to Day 28]) up to 24 weeks (posttreatment phase)
measure: Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24
timeFrame: Baseline (DB induction phase), Weeks 2, 4, 6, 8, 12, 16, 20 and 24 (posttreatment phase)
measure: OL Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score
timeFrame: Days 8, 15, 22 and 28 (OL induction phase)
measure: OL Induction Phase: Change From Baseline (Prior to the First Dose of OL Induction Phase) in MADRS Total Score up to Endpoint OL Induction Phase (Last Post Baseline Assessment Value During the OL Induction Phase [OL: up to Day 28])
timeFrame: Baseline (Prior to first Dose of OL induction phase on Day 1) up to endpoint of OL induction phase (last post baseline assessment value during OL induction phase [OL: up to Day 28])
measure: OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale
timeFrame: Baseline (Prior to first dose of OL induction phase on Day 1), endpoint of OL induction phase (last post baseline assessment value during the OL induction phase [OL: up to Day 28])
Other outcomes:
Locations:
city: Akita
country: Japan
city: Fukui-shi
country: Japan
city: Fukuoka-Shi
country: Japan
city: Fukuoka
country: Japan
city: Gunma
country: Japan
city: Hachinohe-shi
country: Japan
city: Hachioji-shi
country: Japan
city: Hirakata
country: Japan
city: Hiratsuka-shi
country: Japan
city: Hokkaido
country: Japan
city: Ibaraki
country: Japan
city: Ichikawa
country: Japan
city: Kanzaki-gun
country: Japan
city: Karatsu
country: Japan
city: Kashihara
country: Japan
city: Kawasaki
country: Japan
city: Kita-Azumi
country: Japan
city: Kita-Ku
country: Japan
city: Kitakyushu
country: Japan
city: Kobe
country: Japan
city: Kochi
country: Japan
city: Kodaira
country: Japan
city: Komoro-shi
country: Japan
city: Kumamoto
country: Japan
city: Kure
country: Japan
city: Kurume-shi
country: Japan
city: Kyoto
country: Japan
city: Maizuru
country: Japan
city: Morioka
country: Japan
city: Nagakute
country: Japan
city: Nagasaki
country: Japan
city: Okayama-shi
country: Japan
city: Okayama
country: Japan
city: Okinawa
country: Japan
city: Osaka
country: Japan
city: Sapporo-shi
country: Japan
city: Setagaya-ku
country: Japan
city: Shibuya-ku
country: Japan
city: Shinjuku-ku
country: Japan
city: Shinjuku
country: Japan
city: Takatsuki-shi
country: Japan
city: Toyoake
country: Japan
city: Ube
country: Japan
city: Yokohama-shi
country: Japan
city: Yokohama
country: Japan
city: Yonago
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Ohnishi T, Wakamatsu A, Kobayashi H. Different symptomatic improvement pattern revealed by factor analysis between placebo response and response to Esketamine in treatment resistant depression. Psychiatry Clin Neurosci. 2022 Aug;76(8):377-383. doi: 10.1111/pcn.13379. Epub 2022 Jun 9.
citation: Takahashi N, Yamada A, Shiraishi A, Shimizu H, Goto R, Tominaga Y. Efficacy and safety of fixed doses of intranasal Esketamine as an add-on therapy to Oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study. BMC Psychiatry. 2021 Oct 25;21(1):526. doi: 10.1186/s12888-021-03538-y.