Clinical Trials Register

Summary
EudraCT Number:	2020-002905-24
Sponsor's Protocol Code Number:	74304
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-10
Trial 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

Netherlands - Competent Authority

A.2

EudraCT number

2020-002905-24

A.3

Full title of the trial

Efficacy and feasibility of intranasal ketamine on acute suicidality, a double blind
randomized placebo-controlled trial
(Ketamine Trial for Acute suicidalty, KETA)

Effectiviteit en toepasbaarheid van intranasale ketamine op acute suïcidaliteit, een
dubbelblinde gerandomiseerde placebo-gecontroleerde trial (Ketamine
Trial voor Acute suicidaliteit, KETA)

A.3.1

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

Efficacy of ketamine nose-spray on acute suicidal thoughts and behaviou

Effectiviteit van ketamine-neusspray op acute suïcidale gedachten en
gedrag

A.3.2

Name or abbreviated title of the trial where available

Ketamine Trial for Acute suicidality (KETA)

Ketamine Trial voor Acute suïcidaliteit (KETA)

A.4.1

Sponsor's protocol code number

74304

A.5.4

Other Identifiers

Name:

research register UMCG

Number:

202000511

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	University Medical Center Groningen
B.1.3.4	Country	Netherlands
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	ZonMw
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Medical Center Groningen (UMCG
B.5.2	Functional name of contact point	Jurriaan Strous
B.5.3	Address:
B.5.3.1	Street Address	Hanzeplein 1
B.5.3.2	Town/ city	Groningen
B.5.3.3	Post code	9713 AG
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031503616161
B.5.5	Fax number	Neder655821326
B.5.6	E-mail	jurriaanstrous@gmail.com

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	No
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	ketamine/ketalar
D.3.2	Product code	1867-66-9
D.3.4	Pharmaceutical form	Nasal spray, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasal use
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Nasal spray, solution
D.8.4	Route of administration of the placebo	Nasal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute suicidality, which is a rapid increase in suicidal ideation or
behaviour from the patient's 'baseline' in the last 24 hours.

Acute suïcidaliteit, gedefinieerd als een snelle toename in suïcidale
gedachten of gedrag vanaf de 'baseline' van patiënt.

E.1.1.1

Medical condition in easily understood language

Acute suicidality, thoughts about the wish to kill oneself, or behaviour with either the aim to die or a significant likelyhood that one could die because of this behaviour

Acute suïcidaliteit, gedachten over de wens zichzelf van het leven te
willen beroven, of gedrag met het doel te sterven of met een grote
waarschijnlijkheid dat men als gevolg van het gedrag sterft.

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To investigate the anti-suicidal effects of a single dose of intranasal
ketamine in acutely suicidal subjects.

Het onderzoeken van het antisuïcidale effect van een eenmalige dosering van intranasale ketamine in acuut suïcidale proefpersonen.

E.2.2

Secondary objectives of the trial

to assess
-safety
-antidepressant effects
-time-course of the effects
-the number of suicides and suicidal acts
-the pharmacokinetic profile of intranasal ketamine
-the association between the anti-suicidal and the antidepressant effect
-neurobiological markers associated with the response to ketamine using
*structural magnetic resonance imaging (MRI)
*hippocampal and prefrontal magnetic resonance spectroscopy (MRS)
*structural connectivity using diffusion tensor imaging (DTI)
*functional connectivity using magnetic resonance imaging (fMRI)
*blood samples

-het vaststellen van
- veiligheid
- het antidepressieve effect
- het tijdsverloop van het effect
- het aantal suïcides en suïcidepogingen
- het farmacokinetische profiel van intranasale ketamine
- het verband tussen het antisuïcidale en het antidepressieve effect
- neurobiologische markers geassocieerd met de respons op ketamine gemeten middels
*MRI
*hippocampale en prefrontale MRS
*structurele connectiviteit gemeten middels DTI
*functionele connectiviteit als gemeten met fMRI
*bloedsamples

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Acute suicidality
A Beck Scale for Suicide Ideation (BSSI)-score of 7 or above
Subjects are in the age of 18-7

Acute suïcidaliteit
Een BSSI-score van 7 of hoger
Proefpersonen zijn 18 tot 70 jaar oud

E.4

Principal exclusion criteria

1. Earlier participation in this study
2. Psychosis (as a primary diagnosis) (depression with psychotic features will not be an exclusion criterion per se).
3. A diagnosis of schizophrenia or another primary psychotic disorder.
4. A history of PCP- or ketamine addiction.
5. Being under influence of GHB (Substance abuse in the (recent) history
is not an exclusion criterion per se (with the exception of GHB and a high
blood alcohol concentration, and intoxications leading to medical
unstable conditions).
6. A blood alcohol concentration (BAC)of >0.05%
7. A clinically significant and unstable infectious, immunological,
cardiovascular, gastro-intestinal, pulmonal, renal, hepatic, endocrine or haematological disorder, a myocardial infarction, miction problems or a complex surgical problem that needs immediate attention.
8. Presence of any contra-indication for ketamine use, such as severe high blood pressure, a recent myocardial infarction or relevant cardiac problems, severe thyroid problems, severe liver problems, severe kidney problems, epilepsy and increased intracranial pressure.
9. A known hypersensitivity for ketamine.
10. Concomitant use of a MAO-inhibitor.
11. Severe nose congestion or nasal polyps.
12. Pregnancy or giving breastfeeding 13. Women of reproductive age using unreliable contraception.
14. Being unable to answer the questionnaires
15. Legal incompetency with regard to participation in this study
16. No informed consent

1. Eerdere deelname aan deze studie
2. Psychose (als primaire diagnose) (depressie met psychotische kenmerken is niet per definitie een exclusiecriterium).
3. Een diagnose van schizofrenie of een andere primaire psychotische stoornis
4. Een geschiedenis van PCP- of ketamineverslaving/misbruik
5. Onder invloed zijn van GHB (middelenmisbruik is niet per se een
exclusiecriterium, met een GHB-intoxicatie of een BAC van >0,05% of
een intoxicatie die acute medische interventie vereist als uitzondering).
6. Een bloed alcohol concentratie (BAC) van >0,05%
7.Een klinisch significante en onstabiele infectieuze, immunologische,
cardiovasculaire, gastro-intestinale, pulmonale, renale, hepatische,
endocriene of hematologische stoornis, een myocardinfarct,
mictieproblemen of een complex chirurgisch probleem dat onmiddellijke
medische aandacht behoeft.
8. Aanwezigheid van een contra-indicatie voor ketaminegebruik, zoals
een ernstige hoge bloeddruk, een recent myocardinfarct of relevante
cardiale problemen, ernstige leverproblematiek, ernstige
nierproblematiek, epilepsie en verhoogde intracraniële druk.
9. Een bekende hypersensitiviteit voor ketamine.
10. Gelijktijdig gebruik van een MAO-remmer.
11. Ernstige neusverstopping of neuspoliepen
12. Zwangerschap of het geven van borstvoeding
13. Vrouwen in de vruchtbare leeftijd die geen betrouwbare
anticonceptie gebruiken.
14. Niet in staat zijn vragenlijsten in te vullen/te beantwoorden.
15. Niet wilsbekwaam zijn ten aanzien van het geven van informed consent voor deelname aan de studie.
16. Geen informed consent

E.5 End points

E.5.1

Primary end point(s)

Change in suicidality scores on the BSSI between baseline and 180
minutes after 75 mg intranasal ketamine administration compared to 4.0mg intranasal midazolam (placebo

Verandering in acute suïcidaliteit als gemeten met de Beck Scale for
Suicide Ideation (BSSI), 180 minuten na 50mg intranasale ketamine, ten opzichte van 4,0mg intranasale midazolam

E.5.1.1

Timepoint(s) of evaluation of this end point

180 minutes after intervention/comparator

180 minuten na interventie/comparator

E.5.2

Secondary end point(s)

1. Suicidality from baseline to 60 minutes, 180 minutes, one day, three days and one week after one intranasal ketamine administration compared to placebo, as measured with: a. Beck Scale for Suicide Ideation (BSSI) (Dutch version) c. Suicidality item on the Montgomery
Asberg Depression Rating Scale. (MADRS) (Dutch version).
2. Actual number of suicides and suicidal at 60 and 180 minutes, 1, 3 and 7 days after ketamine/midazolam administration.
3. Depressive symptoms as measured with the MADRS from baseline to 60 minutes and 180 minutes, one, three and seven days after one intranasal ketamine administration compared to placebo.
4. Clinical severity and improvement as measured with the CGI
5. Psychotomimetic symptoms, as measured with the SAFTEE (Dutch version) and the CADSS (Dutch version) from baseline to 60 minutes and 180 minutes.
items 6-11 in protocol

Suïcidaliteit ten opzichte van baseline op 60 minuten, 180 minuten,
1,3 en 7 dagen en 6 en 12 maanden na toediening van intranasale
ketamine in vergelijking met placebo, gemeten met -de BSSI
(Nederlandse versie) -het suïcidaliteitsitem op de Montgomery Asberg
Depression Rating Scale (MADRS) (Nederlandse versie)
2. Het aantal suïcides in beide groepen op 60 en 180 minuten, 1, 3 en 7
dagen en 6 en 12 maanden na ketamine/midazolamtoediening.
3. Depressieve symptomen als gemeten met de MADRS t.o.v. baseline op
60 minuten, 180 minuten, 1, 3 en 7 dagen en 6 en 12 maanden na
toediening van de intranasale ketamine, in vergelijking met placebo. 4. Klinische ernst en verbetering als gemeten met de CGI
5. Psychotomimetische symptomen als gemeten met de SAFTEE (Nederlandse versie) en de CADSS (Nederlandse versie) t.o.v. baseline op 60 en 180 minuten na toediening.
items 6-11 in protocol

E.5.2.1

Timepoint(s) of evaluation of this end point

60 minutes, 180 minutes, 1,3 and 7 days after
intervention/comparator

60 minuten, 180 minuten, 1,3 en 7 dagen na
toediening van interventie/comparator

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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

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)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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 last follow-up call of the last subject (one week after his/her visit)

Het laatste telefonisch contact naar de laatst geïncludeerde proefpersoon (1week na inclusie)

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

E.8.9.2

In all countries concerned by the trial days

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:

112

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

112

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)

None

Geen

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

2021-07-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-08

P. End of Trial
P.	End of Trial Status	Ongoing

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