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

A Double-Blind, Double-Randomization, Placebo-Controlled Study of the Efficacy of Intravenous Esketamine in Adult Subjects With Treatment-Resistant Depression

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.

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.

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