A Study of the Efficacy of Intravenous Esketamine in Adult Patients With Treatment-Resistant Depression

NCT ID: NCT01640080

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-27
• Study Completion Date: 2013-06-03

Brief Summary

The purpose of this study is to assess the efficacy of esketamine compared with placebo in improving symptoms of depression in patients with treatment resistant depression.

Detailed Description

This is a double-blind (neither physician nor patient knows the treatment that the patient receives), double-randomization (the study drug is assigned by chance), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), multiple dose titration study in adult patients with treatment resistant depression (TRD). The study will assess the efficacy of esketamine at 24 hours after dosing on Day 1, administered as a 0.40 mg/kg and 0.20 mg/kg intravenous (i.v.) infusion, compared with placebo in improving symptoms of depression in patients with TRD, using the Montgomery-Asberg Depression Rating Scale (MADRS). The study will consist of 3 phases: a screening phase of up to 2 weeks, a 7-day double-blind treatment phase (Day 1 to Day 7), and a 4-week posttreatment (follow up) phase. The interval between the first and last dose of study medication is 3 days. The total study duration for each patient will be a maximum of 7 weeks.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Esketamine (Group 1)

Group Type: EXPERIMENTAL

Esketamine

Intervention Type: DRUG

Type= exact number, number= 0.20, unit= mg/kg, form= intravenous infusion, route= intravenous use. One single intravenous infusion of esketamine 0.20 mg/kg administered on Day 1 and Day 4.

Esketamine (Group 2)

Group Type: EXPERIMENTAL

Esketamine

Intervention Type: DRUG

Type= exact number, number= 0.40, unit= mg/kg, form= intravenous infusion, route= intravenous use. One single intravenous infusion of esketamine 0.40 mg/kg administered on Day 1 and Day 4.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Form= intravenous infusion, route= intravenous use. One single placebo intravenous infusion administered on Day 1 and Day 4.

Interventions

Esketamine

Type= exact number, number= 0.20, unit= mg/kg, form= intravenous infusion, route= intravenous use. One single intravenous infusion of esketamine 0.20 mg/kg administered on Day 1 and Day 4.

Intervention Type: DRUG

Esketamine

Type= exact number, number= 0.40, unit= mg/kg, form= intravenous infusion, route= intravenous use. One single intravenous infusion of esketamine 0.40 mg/kg administered on Day 1 and Day 4.

Intervention Type: DRUG

Placebo

Form= intravenous infusion, route= intravenous use. One single placebo intravenous infusion administered on Day 1 and Day 4.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Be medically stable on the basis of clinical laboratory tests
• Diagnostic for major depressive disorder (MDD) without psychotic features
• Have an inadequate response to at least 1 antidepressant in the current episode of depression and at least one other inadequate treatment response to an antidepressant either in the current episode or in a previous episode
• Women must be not pregnant; women must be postmenopausal, surgically sterile or, if heterosexually active, practicing a highly effective method of birth control during the study and for 3 months after receiving the last dose of study drug
• Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
• Signed informed consent document

Exclusion Criteria

• History of, or current signs and symptoms of diseases or conditions that would make participation not be in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments
• Has uncontrolled hypertension (systolic blood pressure (SBP)> 160 mmHg or diastolic blood pressure (DBP)> 90 mmHg despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment) or any past history of hypertensive crisis
• Has known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or have positive results at screening
• Has a primary diagnosis of current (active) generalized anxiety disorder, panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, anorexia nervosa, or bulimia nervosa
• Has a history or current diagnosis of a psychotic disorder, bipolar disorder, mental retardation, or borderline personality disorders, mood disorder with postpartum onset, somatoform disorders or chronic fatigue syndrome
• Has had major surgery, (eg, requiring general or local anesthesia) within 4 weeks before screening, or will not have fully recovered from surgery, or planned surgery during the time the subject is expected to participate in the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Dave, , Belgium

Ghent, , Belgium

Kortenberg, , Belgium

Lede, , Belgium

Berlin, , Germany

Freiburg im Breisgau, , Germany

Mainz, , Germany

München, , Germany

Gdansk, , Poland

Countries

Belgium; Germany; Poland

References

Lewis S, Romano C, De Bruecker G, Murrough JW, Shelton R, Singh JB, Jamieson C. Analysis of Clinical Trial Exit Interview Data in Patients with Treatment-Resistant Depression. Patient. 2019 Oct;12(5):527-537. doi: 10.1007/s40271-019-00369-8.

Reference Type: DERIVED

PMID: 31270774 (View on PubMed)

Johnson KM, Devine JM, Ho KF, Howard KA, Saretsky TL, Jamieson CA. Evidence to Support Montgomery-Asberg Depression Rating Scale Administration Every 24 Hours to Assess Rapid Onset of Treatment Response. J Clin Psychiatry. 2016 Dec;77(12):1681-1686. doi: 10.4088/JCP.15m10253.

Reference Type: DERIVED

PMID: 28086004 (View on PubMed)

Singh JB, Fedgchin M, Daly E, Xi L, Melman C, De Bruecker G, Tadic A, Sienaert P, Wiegand F, Manji H, Drevets WC, Van Nueten L. Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study. Biol Psychiatry. 2016 Sep 15;80(6):424-431. doi: 10.1016/j.biopsych.2015.10.018. Epub 2015 Nov 3.

Reference Type: DERIVED

PMID: 26707087 (View on PubMed)

Other Identifiers

ESKETIVTRD2001

Identifier Type: OTHER

Identifier Source: secondary_id

2011-005992-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR100843

Identifier Type: -

Identifier Source: org_study_id