Efficacy and Safety of Esketamine in the Treatment of Patients With Treatment Resistant Major Depression

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

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2011-005992-17-DE

Enrollment

Registered

2012-03-06

Start date

2012-05-23

Completion date

Unknown

Last updated

2014-06-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Treatment Resistant Major Depression MedDRA version: 14.1 Level: PT Classification code 10057840 Term: Major depression System Organ Class: 10037175 - Psychiatric disorders

Interventions

Trade Name: Ketanest-S Product Name: Ketanest-S 5 - 5 mg/ml solution for injection Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: ESKETAMINE HYDROCHLORIDE CAS Number: 33643-

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Be a man or woman, 18 to 64 years of age, inclusive. - Be medically stable on the basis of clinical laboratory tests performed at screening. - Meet Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM-IV-TR) diagnostic criteria for recurrent MDD, without psychotic features (DSM-IV, 296.32, or 296.33), - 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. - Have an IDS-C30 total score = 34 at Screening and Day -1. - Hospitalized or agreed to be hospitalized from Day -1 through the completion of study procedures on Day 2 and from Day 3 through the completion of study procedures on Day 4. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: - Has a history of, or current signs and symptoms of, liver or renal insufficiency; hypothyroidism or hyperthyroidism, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbances. Subjects with non-insulin dependent diabetes mellitus who are adequately controlled may participate in the study. - Has uncontrolled hypertension (SBP> 160 mmHg or DBP > 90 mmHg despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment) at Screening; or any past history of hypertensive crisis. - Has a history of previous non-response of depressive symptoms to ketamine/esketamine. - Has any contraindication to the use of esketamine, per local prescribing information. - Has not responded to previous treatment with electroconvulsive therapy (ECT).

Design outcomes

Secondary

Measure	Time frame
Secondary end point(s): 1. Improvement in depressive symptoms, as measured by the change in the MADRS total score from Day 1 (baseline) to Day 3 and from Day 1 to Day 4 in the double-blind treatment phase. 2. Change from Day 1 (baseline) to Day 2 in MDD symptoms using the QIDS-SR16 for esketamine compared to placebo. 3. Change from Day 1 (baseline) to Day 2 in severity of illness using the PGI-S for esketamine compared to placebo. 4. Change from Day 1 (baseline) to Day 2 in patient perspective of global change in MDD since start of study treatment, as measured by the PGIC for esketamine compared to placebo. 5. Change from Day 1 (baseline) over time through Day 7 in the MADRS total score;Timepoint(s) of evaluation of this end point: Day 2, 3, 4, 5, 6, 7	—

Measure

Time frame

Secondary end point(s): 1. Improvement in depressive symptoms, as measured by the change in the MADRS total score from Day 1 (baseline) to Day 3 and from Day 1 to Day 4 in the double-blind treatment phase. 2. Change from Day 1 (baseline) to Day 2 in MDD symptoms using the QIDS-SR16 for esketamine compared to placebo. 3. Change from Day 1 (baseline) to Day 2 in severity of illness using the PGI-S for esketamine compared to placebo. 4. Change from Day 1 (baseline) to Day 2 in patient perspective of global change in MDD since start of study treatment, as measured by the PGIC for esketamine compared to placebo. 5. Change from Day 1 (baseline) over time through Day 7 in the MADRS total score;Timepoint(s) of evaluation of this end point: Day 2, 3, 4, 5, 6, 7

—

Primary

Measure	Time frame
Primary end point(s): The primary efficacy endpoint will be improvement in depressive symptoms, as measured by the change in the MADRS total score from Day 1 (baseline) to Day 2 in the double-blind treatment phase. ;Timepoint(s) of evaluation of this end point: Day 2, 24 hours after dosing;Main Objective: The primary objective of the study is to evaluate the efficacy, safety, and tolerability of esketamine in subjects with treatment resistant depression. Efficacy in improving symptoms compared with a placebo will be assessed by the changes from randomisation to end of week 1 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. ;Secondary Objective: 1. To assess the efficacy versus placebo of esketamine 0.20 mg/kg and 0.40 mg/kg i.v. infusion when administered on both Day 1 and Day 4. using the MADRS, the Clinical Global Impression – Severity and Clinical Global Impression – Improvement. 2. To assess the impact of esketamine 0.20 mg/kg and 0.40 mg/kg i.v. infusion on the patient administered Quick Inventory of Depressive Symptomatology- Self Report, the Patient Global Impression – Severity and the Patient Global Impression of Change. 3. To assess the proportion of responders (subjects who have a reduction in MADRS total score of >50% versus baseline on Day 2, 3, or 4 (prior to dosing) in each of the esketamine dose groups compared to placebo. 4. To evaluate the pharmacokinetics (PK) of esketamine, administered as an i.v. infusion, in subjects with TRD.	—

Measure

Time frame

Primary end point(s): The primary efficacy endpoint will be improvement in depressive symptoms, as measured by the change in the MADRS total score from Day 1 (baseline) to Day 2 in the double-blind treatment phase. ;Timepoint(s) of evaluation of this end point: Day 2, 24 hours after dosing;Main Objective: The primary objective of the study is to evaluate the efficacy, safety, and tolerability of esketamine in subjects with treatment resistant depression. Efficacy in improving symptoms compared with a placebo will be assessed by the changes from randomisation to end of week 1 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. ;Secondary Objective: 1. To assess the efficacy versus placebo of esketamine 0.20 mg/kg and 0.40 mg/kg i.v. infusion when administered on both Day 1 and Day 4. using the MADRS, the Clinical Global Impression – Severity and Clinical Global Impression – Improvement. 2. To assess the impact of esketamine 0.20 mg/kg and 0.40 mg/kg i.v. infusion on the patient administered Quick Inventory of Depressive Symptomatology- Self Report, the Patient Global Impression – Severity and the Patient Global Impression of Change. 3. To assess the proportion of responders (subjects who have a reduction in MADRS total score of >50% versus baseline on Day 2, 3, or 4 (prior to dosing) in each of the esketamine dose groups compared to placebo. 4. To evaluate the pharmacokinetics (PK) of esketamine, administered as an i.v. infusion, in subjects with TRD.

—

Countries

Germany, Poland

Contacts

Public ContactClinical Registry Group

Janssen-Cilag International NV

ClinicalTrialsEU@its.jnj.com(+)3171 524 21 66

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026