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

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2011-005992-17-BE
• Date of registration: 07/03/2012
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: Efficacy and Safety of Esketamine in the Treatment of Patients With Treatment Resistant Major Depression
• Scientific title: A Double-Blind, Double-Randomization, Placebo-Controlled Study of the Efficacy of Intravenous Esketamine in Adult Subjects with Treatment-Resistant Depression
• Date of first enrolment: 15/05/2012
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005992-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Germany, Poland

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion 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:
- 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).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

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

Intervention(s)

Trade Name: Ketanest-S
Product Name: Ketanest-S 5 - 5 mg/ml solution for injection
Pharmaceutical Form: Solution for injection/infusion
CAS Number: 33643-46-8
Other descriptive name: ESKETAMINE HYDROCHLORIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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.

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.

Timepoint(s) of evaluation of this end point: Day 2, 24 hours after dosing

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.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 2, 3, 4, 5, 6, 7

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

Secondary ID(s)

ESKETIVTRD2001

2011-005992-17-DE

Source(s) of Monetary Support

Janssen Research & Development