The Effect of Minocycline on Relapse After Successful Intravenous Ketamine/Minocycline-induced Symptoms Response in Subjects with Depression

• Register: EUCTR
• Last refreshed on: 27 October 2014
• Main ID: EUCTR2012-002954-21-NL
• Date of registration: 01/08/2013
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: The Effect of Minocycline on Relapse After Successful Intravenous Ketamine/Minocycline-induced Symptoms Response in Subjects with Depression
• Scientific title: An exploratory, blinded, randomized, placebo-controlled study in subjects with depressive disorder to investigate the effect of minocycline on relapse after successful intravenous ketamine/minocycline-induced (partial) symptoms response
• Date of first enrolment: 01/08/2013
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002954-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: yes Double blind: no 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

Countries of recruitment

Belgium, Netherlands, Spain

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:
- Diagnostic criteria for moderate to severe major depressive disorder (MDD), without mood incongruent psychotic features, or Bipolar Disorder Type II
- Patients should have an Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) total score = 34 at Screening and at Day 1 (predose)
- Patients with major depressive disorder should have failed at least two adequate treatment courses (dose and duration) with antidepressant therapy, one of which is in the current episode
- Patients should not have received electroconvulsive therapy (ECT) in the current episode but could be those for whom ECT is considered
- Patients with bipolar depression (BPD) Type II must have been taking a stable dose of a mood-stabilizing medication (e.g., lithium, valproate, carbamazepine, lamotrigine, antipsychotic agents) for at least 4 weeks, dosed clinically to target the therapeutic range
- Patients currently taking an antidepressant(s) must have received at least 2 weeks of stable antidepressant therapy at the time of Screening
- Doses of current antidepressant therapies should remain the same for the duration of the study
- Women must be postmenopausal, surgically sterile, or if heterosexually active, practicing a highly effective method of birth control
- Men who are heterosexually active with a woman of childbearing potential 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
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 64
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion criteria:
- Has a current DSM-IV axis I diagnosis other than MDD or BPD Type II at screening (except for co-morbid anxiety disorders)
- Has a history of substance abuse or dependence within 6 months prior to screening evaluation (nicotine and caffeine dependence are not exclusionary)
- Patient is currently taking > 4 psychotropic medications at Day 1 (predose)
- Has an autoimmune disorder such as Crohn’s disease, rheumatoid arthritis, psoriasis currently treated with/requiring treatment with immunomodulatory therapies
- Has any significant cardiovascular, respiratory, neurologic, renal, hepatic, endocrine, immunologic diseases, glaucoma, hypothyroidism or hyperthyroidism based on screening examination
- Has uncontrolled hypertension (diastolic blood pressure = 90 mmHg), despite diet, exercise or a stable dose of an allowed antihypertensive treatment, at Screening or Day 1 (predose)
- Has planned vaccination within 2 weeks prior to the first dose of study medication through 2 weeks after the last dose of study medication
- Has an active infectious disease/current infection
- Has known allergies, hypersensitivity, or intolerance to minocycline or ketamine or its excipients
- Has contraindications to the use of minocycline or ketamine per local prescribing information


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

Health Condition(s) or Problem(s) studied

Depressive Disorder
MedDRA version: 17.0 Level: PT Classification code 10004940 Term: Bipolar II disorder System Organ Class: 10037175 - Psychiatric disorders
MedDRA version: 17.0 Level: PT Classification code 10057840 Term: Major depression System Organ Class: 10037175 - Psychiatric disorders

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

Intervention(s)

Trade Name: Ketamine Panpharma
Product Name: Ketamine Panpharma - solution injectable - 50 mg/5 ml
Pharmaceutical Form: Solution for injection
INN or Proposed INN: KETAMINE HYDROCHLORIDE
Other descriptive name: KETAMINE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Minocin
Product Name: Minocin - hard capsule - 100 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: MINOCYCLINE HYDROCHLORIDE
CAS Number: 13614-98-7
Other descriptive name: MINOCYCLINE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To investigate the safety and tolerability of the administered study medications (i.e., ketamine and minocycline).

To investigate the effect of minocycline on symptoms of depression in ketamine non-responders.

Primary end point(s): The primary efficacy endpoint will be the proportion of subjects who survive relapse-free (among responders).

Timepoint(s) of evaluation of this end point: Day 54 (Week 6) of the 6-week blinded treatment period.

Main Objective: The primary objective of this study is to assess whether the antidepressant response to IV ketamine can be maintained by minocycline compared to placebo.

Secondary Outcome(s)

Secondary end point(s): 1. The change in MADRS total score among non-responders from pre-randomization to end-of-study.
2. Change in the MADRS total score from baseline during the IV ketamine treatment phase.
3. Change in the MADRS total score from baseline after IV ketamine treatment phase.
4. Response (reduction = 50% in MADRS total score relative to baseline) rate during the IV ketamine treatment phase.
5. Time to relapse (among responders) following completion of the IV ketamine infusion schedule.
6. Effect on Columbia Suicide Severity Rating Scale (C-SSRS).

Timepoint(s) of evaluation of this end point: 1. From Day 12 to Day 54.
2. Days 1, 3, 5, 8, 10, and 12.
3. Days 1, 20, 27, 34, 41, 48, and 54.
4. Days 1, 3, 5, 8, 10 and 12.
5. Day 12 to Day 54.
6. Day 1, 12 & 54.

Secondary ID(s)

KETIVEDI2001

2012-002954-21-BE

Source(s) of Monetary Support

Janssen Research & Development