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

Condition(s) targeted: Depressive Disorder

Intervention: Minocycline (Drug); Placebo (Drug); Ketamine (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: Janssen Research & Development, LLC

Official(s) and/or principal investigator(s):
Janssen Research & Development, LLC Clinical Trial, Study Director, Affiliation: Janssen Research & Development, LLC

The purpose of this study is to assess whether the antidepressant effect from intravenous (IV) ketamine treatment can be maintained by minocycline compared to placebo after IV ketamine treatment is stopped.

Official 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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Proportion of patients (among responders) who survive relapse-free

Secondary outcome:

Change in MADRS total score among non-responders from pre-randomization to end-of-study

Change in the MADRS total score from baseline during IV ketamine treatment phase

Change in the MADRS total score from baseline after IV ketamine treatment phase

Response (reduction ≥ 50% in MADRS total score relative to baseline) rate during IV ketamine treatment phase

Time to relapse (among responders) following completion of the IV ketamine infusion schedule and after first dose of minocycline/placebo

Change in C-SSRS from baseline to any time in the study

Detailed description: This is a placebo-controlled (i. e., an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), double-blind (neither physician nor patient knows the treatment that the patient receives) randomized (the drug is assigned by chance) study in patients with Major Depressive Disorder (MDD) and Bipolar Disorder Type II. The study is designed to assess whether the antidepressant response to treatment with intravenous (IV) ketamine can be maintained by treatment with minocycline in patients with MDD and Bipolar Depression Type II (compared to placebo). Both hospitalized patients as well as patients being treated as an outpatient for their current episode of depression can qualify for participation in this study. The study has four sequential phases: if eligibility for the study has been confirmed during the 21-day screening phase, the patients will enter a 12-day open-label (ie, patient and physician know the intervention that is being administered) treatment phase during which the patient will receive 6 open-label IV infusions of 0. 5 mg/kg ketamine on Day 1, 3, 5, 8, 10 and 12 in combination with open-label minocycline, orally administered twice daily. All patients will remain at the study site for at least 4 hours after the IV ketamine administrations. Response to treatment will be assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) which is designed to measure the overall severity of depressive symptoms. Patients responding to ketamine/minocycline treatment will be randomized to receive minocycline or placebo for 6 weeks during a 6-week blinded treatment phase or until relapse. A patient will be defined as a "ketamine responder" if there is a 50% or more decrease in comparison to baseline values (Day 1 predose) in the MADRS total score performed at 3 to 4 hours postdose on Days 8, 10, or 12, with a 40% or more decrease from baseline in the MADRS total score on Day 12. Patients not responding to treatment with ketamine/minocycline will be given the option to receive 100 mg minocycline twice daily as open-label treatment for a maximum of 6 weeks. The patients (both responders and non-responders) will have weekly visits following last dose of ketamine until Day 54 (responders/non-responders) or until relapse (responders) whichever comes first, to determine the duration of the antidepressant effect and to assess safety and tolerability after completion of treatment. Upon completion of the study (Day 54) or at time of relapse all patients will have an end-of-study visit. All patients can return to standard of care treatment at the end of the study. The total study duration for each patient will be maximally 11 weeks.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnostic criteria for moderate to severe major depressive disorder (MDD), without

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 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 diagnosis of substance abuse or dependence within 6 months prior to screening

evaluation (nicotine and caffeine dependence are not exclusionary)

- Patient is currently taking more than 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, or immunologic diseases 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

Duffel, Belgium

Lede, Belgium

Leuven, Belgium

Besancon, France

Clermont Ferrand, France

Nimes Cedex 9, France

Leiden, Netherlands

Alicante, Spain

Barcelona, Spain

Coslada, Spain

Madrid, Spain

Zamora, Spain

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

Starting date: June 2013
Last updated: June 29, 2015