A Study to Evaluate the Safety and Efficacy of Intranasal Esketamine in Treatment-resistant Depression

NCT01998958 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: CR1029682013-004005-11JNJ-54135419ESKETINTRD2003
• Study Type: interventional
• Target: 108
• Locations: 3 countries
• Sites: 25

Brief Summary

The purpose of this study is to assess the efficacy and dose response of intranasal esketamine (Panel A: 28 mg, 56 mg, and 84 mg and Panel B: 14 mg and 56 mg) compared with placebo in improving depressive symptoms in participants with treatment-resistant depression (TRD).

Conditions

Treatment Resistant Depressive Disorder

Keywords

Treatment resistant depressive disorder; Intranasal esketamine; Efficacy; SYNAPSE; JNJ-54135419

Outcome Measures

Primary Outcomes (2)

• Panel A and B: Change From Baseline (Day 1) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Day 8- Analysis of Covariance (ANCOVA) Analysis

  MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. A negative change in score indicates improvement.

  Baseline (Day 1) and Endpoint (Day 8) of Period 1

• Panel A and B: Change From Baseline (Day 8) in Montgomery Asberg Depression Rating Scale Total Score at Day 15- ANCOVA Analysis

  MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. A negative change in score indicates improvement.

  Baseline (Day 8) and Endpoint (Day 15) of Period 2

Secondary Outcomes (14)

• Panel A and B: Percentage of Participants With Sustained Response Based on MADRS Total Score in Participants Who Have Completed the Double-Blind Phase and Received the Same Treatment for Both Periods

  Day 2 Up to Day 15

• Panel A and B: Percentage of Participants With Sustained Response Based on MADRS Total Score in Participants Who Received the Same Treatment for Both Periods, Including Participants Who Did Not Complete the Double-blind Phase

  Day 2 Up to Day 15

• Panel A and B: Percentage of Participants With Response Based on MADRS Total Score

  Period 1: Days 1 (2 hour), 2 and 8 of Double-blind Phase

• Panel A and B: Percentage of Participants With Response Based on MADRS Total Score

  Period 2: Days 1 (2 hour), 2 and 8 of Double-blind Phase

• Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase

  Days 1, 2 and 8 of Double-blind Phase of Period 1

Study Arms (5)

Esketamine 14 mg

EXPERIMENTAL

Participants in Panel B will self-administer intranasal esketamine 14 milligram or placebo on Days 1, 4, 8, and 11 during the double-blind phase and intranasal esketamine on Days 15, 18, 22, and 25 during the optional open-label phase. During the optional open-label phase, participants will start with treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability).

Drug: Esketamine 14 mg; Drug: Esketamine 56 mg; Drug: Placebo

Esketamine 28 mg

EXPERIMENTAL

Participants in Panel A will self-administer intranasal esketamine 28 mg or placebo on Days 1, 4, 8, and 11 during the double-blind phase and intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60, and 74 during the optional open-label phase. During the optional open-label phase, all participants will start treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability).

Drug: Esketamine 28 mg; Drug: Esketamine 56 mg; Drug: Placebo

Esketamine 56 mg

EXPERIMENTAL

Participants in Panel A and Panel B will self-administer intranasal esketamine 56 mg or placebo on Days 1, 4, 8, and 11 during the double-blind phase. During the optional open-label phase, participants in Panel A will self-administer intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60, and 74 and participants in Panel B will self-administer intranasal esketamine on Days 15, 18, 22, and 25. During the optional open-label phase, all participants will start treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability).

Drug: Esketamine 56 mg; Drug: Placebo

Esketamine 84 mg

EXPERIMENTAL

Participants in Panel A will self-administer intranasal esketamine 84 mg or placebo on Days 1, 4, 8, and 11 during the double-blind phase and intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60, and 74 during the optional open-label phase. During the optional open-label phase, all participants will start treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability).

Drug: Esketamine 56 mg; Drug: Esketamine 84 mg; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Participants in Panel A and B will self-administer intranasal placebo on Days 1 and 4 during the double-blind phase. Depending on response on Day 8, participants will receive intranasal placebo on Days 8 and 11 or be re-randomized to receive intranasal placebo or esketamine at a dose of 28 mg, 56 mg, or 84 mg (Panel A) or 14 mg or 56 mg (Panel B) on Day 8 and Day 11.

Drug: Esketamine 14 mg; Drug: Esketamine 28 mg; Drug: Esketamine 56 mg; Drug: Esketamine 84 mg; Drug: Placebo

Interventions

Esketamine 14 mg DRUG

1 to 6 sprays of esketamine 14 mg self-administered as an intranasal formulation for 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable during the optional open-label phase for up to 4 days

Esketamine 14 mg; Placebo

Esketamine 28 mg DRUG

1 to 6 sprays of esketamine 28 mg self-administered as an intranasal formulation for 4 days (Days 1,4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days

Esketamine 28 mg; Placebo

Esketamine 56 mg DRUG

1 to 6 sprays of esketamine 56 mg self-administered as an intranasal formulation for up to 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days

Esketamine 14 mg; Esketamine 28 mg; Esketamine 56 mg; Esketamine 84 mg; Placebo

Esketamine 84 mg DRUG

1 to 6 sprays of esketamine 84 mg self-administered as an intranasal formulation for up to 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days

Esketamine 84 mg; Placebo

Placebo DRUG

1 to 6 sprays of placebo self-administered as an intranasal formulation for 2 days (Days 1 and 4) or depending on response on Day 8, for 4 days (Days 1,4, 8, 11) during the double-blind phase

Esketamine 14 mg; Esketamine 28 mg; Esketamine 56 mg; Esketamine 84 mg; Placebo

Eligibility Criteria

• Age: 20 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must meet Diagnostic and Statistical Manual of Mental Disorders -Fourth Edition -Text Revised (DSM-IV-TR) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment, and confirmed by the Mini International Neuropsychiatric Interview (MINI)-Participant's major depressive episode and treatment response must be deemed "valid" by remote independent raters-Participant must have had an inadequate response to at least 2 antidepressants, at least one of which is in the current episode of depression; the antidepressant treatment response questionnaire (ATRQ) will be used to assess antidepressant treatment response during the current episode; prior medication history will be used to determine antidepressant treatment response in prior episode(s) -Have an Inventory of Depressive Symptoms-Clinician rated, 30-item (IDS-C30) total score \>=34 at Screening and predose at Day 1

You may not qualify if:

• Participant has a current DSM-IV-TR diagnosis of bipolar and related disorders, intellectual disability, or cluster b personality disorder (e.g., borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder) -Participant has a current or prior DSM-IV-TR diagnosis of a psychotic disorder, MDD with psychosis, post-traumatic stress disorder (PTSD), or obsessive compulsive disorder (OCD) -Anatomical or medical conditions that may impede delivery or absorption of study medication (e.g., undergone facial reconstruction, rhinoplasty, significant structural or functional abnormalities of the nose or upper airway; obstructions or mucosal lesions of the nostrils or nasal passages; undergone sinus surgery in the previous 2 years; signs and symptoms of rhinitis) -Has an abnormal or deviated nasal septum with any 1 or more of the following symptoms: blockage of 1 or both nostrils, nasal congestion (especially 1-sided), frequent nosebleeds, frequent sinus infections, and at times has facial pain, headaches, and postnasal drip -Has a history of substance abuse (drug or alcohol) or dependence (except nicotine or caffeine) within the previous 1 year of the screening visit -Participant has known allergies, hypersensitivity, intolerance, or contraindication to esketamine/ketamine or its excipients

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (25)

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Birmingham, Alabama, United States

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Garden Grove, California, United States

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Hartford, Connecticut, United States

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Jacksonville, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Hoffman Estates, Illinois, United States

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Rockville, Maryland, United States

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Cedarhurst, New York, United States

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New York, New York, United States

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Allentown, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Memphis, Tennessee, United States

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Lede, Belgium

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Akita, Japan

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Hiroshima, Japan

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Ichikawa, Japan

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Kanzaki, Japan

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Kashihara, Japan

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Kitakyushu, Japan

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Kodaira, Japan

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Kumamoto, Japan

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Nagano, Japan

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Shibukawa, Japan

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Related Publications (2)

• Perez-Ruixo C, Rossenu S, Zannikos P, Nandy P, Singh J, Drevets WC, Perez-Ruixo JJ. Population Pharmacokinetics of Esketamine Nasal Spray and its Metabolite Noresketamine in Healthy Subjects and Patients with Treatment-Resistant Depression. Clin Pharmacokinet. 2021 Apr;60(4):501-516. doi: 10.1007/s40262-020-00953-4. Epub 2020 Oct 31.

  PMID: 33128208 DERIVED

• Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, Thase ME, Winokur A, Van Nueten L, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):139-148. doi: 10.1001/jamapsychiatry.2017.3739.

  PMID: 29282469 DERIVED

Related Links

• A Double-Blind, Doubly-Randomized, Placebo-Controlled Study of Intranasal Esketamine in an Adaptive Treatment Protocol to Assess Safety and Efficacy in Treatment-Resistant Depression

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Esketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Senior Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: December 3, 2013
• Study Start: January 27, 2014
• Primary Completion: July 21, 2015
• Study Completion: September 25, 2015
• Last Updated: April 29, 2025
• Results First Posted: June 12, 2019

Record last verified: 2025-04

Locations

US (14); BE (1); JP (10)