Clinical Trials Register

Summary
EudraCT Number:	2014-001968-35
Sponsor's Protocol Code Number:	SPIROTREAT
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-01-23
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

Germany - BfArM

A.2

EudraCT number

2014-001968-35

A.3

Full title of the trial

Add-on spironolactone for the treatment of schizophrenia

Evaluation der Effektivität der add-on Behandlung von Spironolacton bei Patienten mit einer Schizophrenie

A.3.1

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

Add-on spironolactone for the treatment of schizophrenia

Evaluation der Effektivität der add-on Behandlung von Spironolacton bei Patienten mit einer Schizophrenie

A.3.2

Name or abbreviated title of the trial where available

SPIROTREAT

A.4.1

Sponsor's protocol code number

SPIROTREAT

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	Klinikum der Universität München - AöR vertreten durch den Vorstand des Bereiches umanmedizinH
B.1.3.4	Country	Germany
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Muenchner Studienzentrum
B.5.2	Functional name of contact point	Beate Schossow
B.5.3	Address:
B.5.3.1	Street Address	Ismaninger Str. 22
B.5.3.2	Town/ city	Muenchen
B.5.3.3	Post code	81675
B.5.3.4	Country	Germany
B.5.4	Telephone number	00498941406469
B.5.5	Fax number	00498941406322
B.5.6	E-mail	beate.schossow@mri.tum.de

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	Spironolacton HEXAL
D.2.1.1.2	Name of the Marketing Authorisation holder	Hexal
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Spironolacton HEXAL
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	52-01-7
D.3.9.2	Current sponsor code	SPIROTREAT
D.3.9.3	Other descriptive name	SPIRONOLACTON
D.3.9.4	EV Substance Code	SUB10631MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	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	Spironolacton HEXAL
D.2.1.1.2	Name of the Marketing Authorisation holder	HEXAL
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Spironolacton HEXAL
D.3.2	Product code	C03DA01
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	52-01-7
D.3.9.2	Current sponsor code	SPOIROTREAT
D.3.9.3	Other descriptive name	SPIRONOLACTONE
D.3.9.4	EV Substance Code	SUB10631MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100 (2x50mg)
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	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Schizophrenia

Schizophrenie

E.1.1.1

Medical condition in easily understood language

Schizophrenia

Schizophrenie

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10039643
E.1.2	Term	Schizophrenic psychoses
E.1.2	System Organ Class	100000004873

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary endpoint: Improvement of working memory in n-back after 3 weeks.

E.2.2

Secondary objectives of the trial

Secondary endpoints: Improvement of other neurocognitive functions after 3 and 12 weeks (verbal memory, working speed), changes in psychopathology of PANSS and CDSS, changes in CGI and GAF, occurrence of single side effects, changes of cortical inhibition, changes in ERBB4 metabolic pathway

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Essential inclusion Criteria:
Male and female patients with schizophrenia (ICD-10 Criteria), no longer in acute phase of illness (PANSS Total ≤ 75, CGI ≤ 4), duration of illness > 6 months, age between 18 and 65 years
Have need for a combination treatment with a maximum of 2 antipsychotics. Excluded antipsychotics can be found under 4.3.

Wesentliche Einschlusskriterien: Männliche und weibliche Patienten mit Schizophrenie (ICD-10 Kriterien), die sich nicht mehr in der akuten Krankheitsphase befinden (PANSS Total ≤ 75, CGI ≤ 4), Krankheitsdauer > 6 Monate, Alter zwischen 18 und 65 Jahren
Notwendigkeit für eine Kombinationsbehandlung mit maximal 2 Antipsychotika haben. Ausgeschlossene Antipsychotika finden sich unter 4.3.

E.4

Principal exclusion criteria

Essential exclusion Criteria:
Female Patients: Pregnancy, no medically-approved methods of contraception. Current suicidality as well as injuries to others, severe neurological and internistic comorbidities, known and assumed non-compliance regarding intake of medication, current antipsychotic therapy with clozapine, antipsychotic treatment with exclusively a renal eliminable compound (amisulprid), planned antipsychotic combination treatment, no new dosing of mood stabilisers or antidepressants during 3-week intervention phase. An already existing mood stabiliser therapy (excluding lithium) or antidepressant therapy (excluding renal eliminable antidepressant) can be continued in unaltered dose. Alcohol- or substance abuse during the last 6 months before inclusion into study; nicotine and coffee are excluded. Epileptic seizures in anamnesis (only for additional examination TMS with separate Informed Consent Form), known intolerance of the respective study medication, current anuresis or acute kidney failure, kidney insufficiency (creatinine clearance < 30 ml/min per 1.73 m² body surface, resp. serum-creatinine > 1.8 mg/dl), known clinically relevant hyperkalaemia or hyponatraemia, known clinically relevant hypotension (RR < 100/80), simultaneous application of potassium-sparing diuretics, ACE inhibitors or AT-II antagonists, NSAR, thiazide-diuretics, carbenoxolon, digoxin, neomycin, lithium. Missing capacity for consent or hospitalisation of patients against their will, insufficient knowledge of the German language, state of treatment resistance or never treated schizophrenia.
Known clinical need for antipsychotic combination treatment with more than two antipsychotics.

Wesentliche Ausschlusskriterien:
Bei weiblichen Teilnehmern: Bestehende Schwangerschaft , keine sichere Verhütungsmetholde entsprechend der CTFG-Leitlinie
Gegenwärtige Suizidalität sowie Fremdgefährdung, schwere neurologische und internistische Komorbiditäten, bekannte oder vermutete non-compliance hinsichtlich der Medikamenteneinnahme, aktuelle antipsychotische Therapie mit Clozapin, antipsychotische Behandlung mit einem auschließlich renal eliminierbaren Präparat (z.B. Amisulprid), bekannte klinische
bekannte klinische Notwendigkeit einer antipsychotischen Kombinationsbehandlung mit mehr als zwei Antipsychotika.
Geplante Eindosierung von Stimmungsstabilisierern oder Antidepressiva während der 3-wöchigen Interventionsphase.
Eine vorher bestehende Therapie mit einem Stimmungsstabilisierer (außer Lithium) oder einem Antidepressivum (außer renal eliminierbarer Antidepressiva) kann in unveränderter Dosis fortgesetzt werden. Alkohol- oder Substanzabhängigkeit innerhalb der letzten sechs Monate vor Studieneinschluss. Nikotin und Koffein sind hiervon ausgenommen. Epileptische Anfälle in der Anamnese (gilt nur für die TMS Zusatzuntersuchung mit separater Patienteninformation/Einwilligungserklärung), bekannte Unverträglichkeit zu einem der Studienmedikamente, bestehende Anurie oder akutes Nierenversagen, Niereninsuffizienz (Kreatinin Clearance unter 30 ml/min pro 1.73 m² Körperoberfläche bzw. Serum-Kreatinin über 1.8 mg/dl), bekannte klinisch relevante Hyperkaliämie oder Hyponatriämie, bekannte klinisch relevante Hypotonie (RR < 100/80), gleichzeitige Anwendung von Kalium-sparenden Diuretika, ACE-Hemmern oder ATII-Antagonisten, NSAR, Thiaziddiurektika, Carbenoxolon, Digoxin, Neomycin, Lithium, fehlende Einwilligungsfähigkeit oder Unterbringung gegen den Willen des Patienten, unzureichende Kenntnis der deutschen Sprache, Zustand der Behandlungsresistenz oder noch nie behandelte Schizophrenie

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint: Improvement of working memory in n-back (2-back hits) after 3 weeks.

Verbesserung des Arbeitsgedächtnisses im n-back (2-back Treffer) nach drei Wochen.

E.5.1.1

Timepoint(s) of evaluation of this end point

3 weeks

3 Wochen

E.5.2

Secondary end point(s)

Secondary endpoints: Improvement of other neurocognitive functions after 3 and 12 weeks (further parameters of working memory) verbal memory, working speed), changes in psychopathology of PANSS and CDSS, changes in CGI and GAF, occurrence of single side effects, changes of cortical inhibition, changes in ERBB4 metabolic pathway. Comparison of both verum arms vs. placebo

Verbesserung anderer neurokognitiver Funktionen nach drei und acht Wochen (weitere Arbeitsgedächtnisparameter, verbales Gedächtnis, Arbeitsgeschwindigkeit), Veränderung in der Psychopathologie nach PANSS und CDSS, Veränderung im CGI und GAF, Auftreten von einzelnen Nebenwirkungen, Veränderung der kortikalen Inhibition, Veränderung im ERBB4 Stoffwechselweg. Vergleich der beiden Verum-Arme gepoolt vs. Plazeboarm

E.5.2.1

Timepoint(s) of evaluation of this end point

after 3 and 12 weeks

nach drei und acht Wochen

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

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

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)

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

Last Patient Last Visit

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

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)

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

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

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)

After the end of the study patients regardless of whether the study end according to the protocol or early / non-terminated according to protocol, the patient get the antipsychotic therapy which they had taken. Even switching to a different medication is possible.

Nach Ende der Studie können Patienten unabhängig davon, ob die Studie protokollgemäß oder vorzeitig/nicht-protokollgemäß beendet wurde, mit demjenigen Antipsychotikum weiterbehandelt werden, das sie eingenommen hatten. Auch eine Umstellung auf ein anderes Medikament ist möglich.

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

2015-02-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-08-11

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