Clinical trial NCT01640080: A Study of the Efficacy of Intravenous Esketamine in Adult Patients With Treatment-Resistant Depression
Official title: A Double-Blind, Double-Randomization, Placebo-Controlled Study of the Efficacy of Intravenous Esketamine in Adult Subjects With Treatment-Resistant Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: Major depressive disorder
Treatment resistant depression
Depression
Esketamine
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-07-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
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 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.

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

Primary outcomes:
measure: Change from Day 1 (baseline) to Day 2 in the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind treatment phase
timeFrame: Day 1 (baseline), Day 2
Secondary outcomes:
measure: Change from Day 1 (baseline) to Day 4 in Major Depressive Disorder (MDD) symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind treatment phase
timeFrame: Day 1 (baseline), Day 4
measure: Change from Day 1 (baseline) to Day 35 in Major Depressive Disorder (MDD) symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) total score during the posttreatment phase
timeFrame: Day 1 (baseline), Day 35
measure: The number of patients who have a reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score of >50% versus baseline on Day 2
timeFrame: Day 1 (baseline), Day 2
measure: Change from Day 1 (baseline) to Day 4 in Major Depressive Disorder (MDD) symptoms using the Quick Inventory of Depressive Symptomatology-Self Report- 14-Item (QIDS-SR14)
timeFrame: Day 1 (baseline), Day 4
measure: Change from Day 1 (baseline) to Day 14 in Major Depressive Disorder (MDD) symptoms using the Quick Inventory of Depressive Symptomatology-Self Report-16-item (QIDS-SR16)
timeFrame: Day 1 (baseline), Day 14
measure: Change from Day 1 (baseline) to Day 7 in severity of illness using the Clinical Global Impression- Severity (CGI-S) for esketamine compared to placebo
timeFrame: Day 1 (baseline), Day 7
measure: Change from Day 1 (baseline) to Day 7 of global change in Major Depressive Disorder (MDD) since start of study treatment, as measured by the Clinical Global Impression- Improvement (CGI-I)
timeFrame: Day 1 (baseline), Day 7
measure: Change from Day 1 (baseline) to Day 7 in severity of illness using the Patient Global Impression - Severity (PGI-S) for esketamine compared to placebo
timeFrame: Day 1 (baseline), Day 7
measure: Change from Day 1 (baseline) to Day 7 in patient perspective of global change in Major Depressive Disorder (MDD) since start of study treatment, as measured by the Patient Global Impression of Change (PGI-C)
timeFrame: Day 1 (baseline), Day 7
measure: Change from Day 4 to Day 7 in Major Depressive Disorder (MDD) symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind treatment phase
timeFrame: Day 4, Day 7
measure: The number of patients who have a reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score of >50% versus baseline on Day 3
timeFrame: Day 1 (baseline), Day 3
measure: The number of patients who have a reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score of >50% versus baseline on Day 4
timeFrame: Day 1 (baseline), Day 4
measure: Change from Day 4 to Day 7 in Major Depressive Disorder (MDD) symptoms using the Quick Inventory of Depressive Symptomatology-Self Report- 14-Item (QIDS-SR14)
timeFrame: Day 4, Day 7
Other outcomes:
Locations:
city: Dave
country: Belgium
city: Gent
country: Belgium
city: Kortenberg
country: Belgium
city: Lede
country: Belgium
city: Berlin
country: Germany
city: Freiburg
country: Germany
city: Mainz
country: Germany
city: Munchen
country: Germany
city: Gdansk
country: Poland
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.