Clinical Trials Register

Summary
EudraCT Number:	2015-002020-37
Sponsor's Protocol Code Number:	20/15
National Competent Authority:	Ireland - HPRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-08-04
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Ireland - HPRA

A.2

EudraCT number

2015-002020-37

A.3

Full title of the trial

Ketamine for relapse prevention in recurrent depressive disorder: a randomised,
controlled pilot trial

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Ketamine for relapse prevention in recurrent depressive disorder: a randomised,
controlled pilot trial

A.3.2

Name or abbreviated title of the trial where available

KINDRED Trial

A.4.1

Sponsor's protocol code number

20/15

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	St Patrick's Mental Health Services
B.1.3.4	Country	Ireland
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	None
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	St Patrick's University Hospital
B.5.2	Functional name of contact point	Martha Finnegan
B.5.3	Address:
B.5.3.1	Street Address	James' St
B.5.3.2	Town/ city	Dublin 8
B.5.3.3	Post code	D8
B.5.3.4	Country	Ireland
B.5.4	Telephone number	0035312493385
B.5.6	E-mail	mfinneg@tcd.ie

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Ketalar
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Healthcare Ireland
D.2.1.2	Country which granted the Marketing Authorisation	Ireland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ketalar 10mg/ml Solution for Injection/Infusion
D.3.2	Product code	N01AX03
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Intravenous drip use (Noncurrent)
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Hypnovel 10mg/5ml solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Products Limited
D.2.1.2	Country which granted the Marketing Authorisation	Ireland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Hypnovel 10mg/5ml solution for injection
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Intravenous drip use (Noncurrent)
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Recurrent depressive disorder

E.1.1.1

Medical condition in easily understood language

Recurrent depressive disorder

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10057840
E.1.2	Term	Major depression
E.1.2	System Organ Class	10037175 - Psychiatric disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The aim of this trial is to assess ketamine for reducing relapse in successfully treated recurrent depressive disorder (RDD).
We hypothesise that ketamine will reduce six month relapse rates following successful treatment of depression.

E.2.2

Secondary objectives of the trial

(I) To assess safety and tolerability of repeated (4) infusions of ketamine vs. midazolam in the population of
patients with successfully treated RDD
(II) To explore the role of ketamine-induced changes in established peripheral blood neuroplasticity
biomarkers for (i) monitoring a biological response to ketamine within the first infusion session and also (ii) for
evaluating this biological response in predicting lower relapse rates in the following six months.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria:
Patients ≥18 years with DSM-V criteria for recurrent depressive disorder (RDD), a 24-item Hamilton Rating Scale
for Depression (HRSD-24) score of ≥21, and voluntarily admitted to SPUH for treatment of the acute depressive
episode will be invited to participate. The DSM-V criteria for RDD are ≥2 previous depressive episodes with at
least 2-months (consecutive) subthreshold or no symptoms in between. (The inclusion criterion for this trial was amended on 15.9.16 and the enriched criterion of >3 episodes of depression has been removed). HRSD-24 will be repeated on a weekly basis for the duration of the
inpatient stay. Upon meeting response criteria, patients will be invited to take part in the randomised controlled
pilot trial. They will be assessed by physical examination, routine haematology and biochemistry investigations,
and an ECG to screen for any medical conditions that might affect ability to be treated with ketamine.
For the randomised pilot trial, RDD patients must have (i) received antidepressant treatment for the
acute depressive episode, whether pharmacological, psychotherapeutic or multidisciplinary, (ii) achieved at least
response criteria (i.e. ≥60% decrease from baseline HRSD-24 score and score ≤16), (iii) have a nominated adult
who can stay with them for 24-hours on out-patient treatment days, (iv) have a Mini-Mental State Examination
(MMSE) score of ≥24, and (v) be able to provide informed consent.

E.4

Principal exclusion criteria

Exclusion criteria:
Current involuntary admission, any condition rendering patients medically unfit for ketamine or midazolam;
active suicidal intention; dementia; lifetime history of bipolar disorder, post-traumatic stress disorder, or Axis 1
diagnosis other than RDD; ECT for treatment of the index depressive episode; alcohol/substance abuse in
previous six-months; pregnancy or inability to confirm use of adequate contraception during the trial;
inability/refusal to consent.

E.5 End points

E.5.1

Primary end point(s)

The focus of a pilot trial’s outcomes is on trial process with assessment of the primary clinical outcome
being secondary because the pilot itself is not designed to measure efficacy. Process outcomes that will inform
a future definitive ketamine relapse prevention trial include the following:
• recruitment methods and rate
• willingness of participants to be randomised
• willingness of participants to complete assessments
• randomisation
• success of blinding
• ability to administer a course of ketamine infusions
• adherence to allocated treatment
• adherence to follow-up
• reasons for drop-out from treatment
• reasons for drop-out from follow-up
• a 95% confidence interval for the difference between the ketamine

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint of this pilot trial is successful completion of the trial protocol. Process outcomes such as recruitment and retention rates are the primary focus. Recruitment will cease when 40 participant have been randomised.

E.5.2

Secondary end point(s)

Clinical outcomes are secondary. The primary clinical outcome is relapse rate at six months, measured using the objectively-rated 24-item Hamilton Rating Scale for Depression (HRSD-24). Standard criteria for depression severity, treatment response, remission and relapse will be used (please see definitions in “assessments”) in a six-month follow-up schedule which involves the HRSD-24 and other instruments at weeks 12, 20 and 26 post-treatment-response. Safety and tolerability outcomes consist of psychotomimetic, dissociative, cognitive and physical health effects of repeated ketamine infusions, measured before, during and after infusions using a range of validated instruments.

E.5.2.1

Timepoint(s) of evaluation of this end point

Participants will be assessed at baseline (on admission to hospital), and on weekly basis using the primary clinical outcome, the HRSD-24. Those who are identified as responders to acute treatment according to standard criteria, will be invited to be randomised to an eight-week course of ketamine vs. midazolam infusions. The HRSD-24 will be assessed at each infusion session and at weeks 6; 8;12; 20 and 26. Cognitive outcomes will be assessed following randomization and repeated at week 26. Tolerability outcomes e.g. the Young Mania Rating Scale, Brief Psychiatric Rating Scale etc, will be assessed before, during and after each infusion session. In total, follow-up will take place over six months.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

This is primarily a pilot trial to assess the feasibility of the proposed protocol.

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Midazolam

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end-of-trial will constitute the final follow up visit by the final participant.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

People with mental illness - must be included to answer research question

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

A six-month follow-up procedure as detailed above. NO further treatment following randomised treatment phase.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-07-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-09-03

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2018-05-28

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