Clinical Trials Register

Summary
EudraCT Number:	2010-022307-22
Sponsor's Protocol Code Number:	BergenPsychosisProject2
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-04-11
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

Norway - NOMA

A.2

EudraCT number

2010-022307-22

A.3

Full title of the trial

The Bergen Psychosis Project 2

A.3.1

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

The Bergen Pscychosis Project 2

A.3.2

Name or abbreviated title of the trial where available

BP2

A.4.1

Sponsor's protocol code number

BergenPsychosisProject2

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	Haukeland University Hospital, Division of Psychiatry
B.1.3.4	Country	Norway
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	Haukeland University Hospital, Division of Psychiatry;
B.4.2	Country	Norway
B.4.1	Name of organisation providing support	The Western Norway Regional Health Authority
B.4.2	Country	Norway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Haukeland University Hospital, Division of Psychiatry, Department of Research
B.5.2	Functional name of contact point	Department of Research, Sandviken
B.5.3	Address:
B.5.3.1	Street Address	Sandviksleitet 1
B.5.3.2	Town/ city	Bergen
B.5.3.3	Post code	N-5035
B.5.3.4	Country	Norway
B.5.4	Telephone number	+4755958400
B.5.5	Fax number	+4755958436
B.5.6	E-mail	erij@helse-bergen.no

D. IMP Identification
D.IMP: 1
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	Solian
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Aventis
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Amisulpride
D.3.4	Pharmaceutical form	Tablet
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.3.8	INN - Proposed INN	AMISULPRIDE
D.3.9.1	CAS number	71675859
D.3.9.2	Current sponsor code	Solian
D.3.9.3	Other descriptive name	Solian
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	50 to 400
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	Yes
D.3.11.13.1	Other medicinal product type	Chemical, synthetic medicinal product
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	Abilify
D.2.1.1.2	Name of the Marketing Authorisation holder	Otsuka Pharmaceutical Europe Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Aripiprazole
D.3.4	Pharmaceutical form	Tablet
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.3.8	INN - Proposed INN	ARIPIPRAZOLE
D.3.9.1	CAS number	129722-12-9
D.3.9.2	Current sponsor code	Abilify
D.3.9.3	Other descriptive name	Abilify
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 to 30
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	Yes
D.3.11.13.1	Other medicinal product type	Chemical, synthetic medicinal product
D.IMP: 3
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	Zyprexa, Olanzapin
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Zyprexa, Olanzapine
D.3.4	Pharmaceutical form	Tablet
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.3.8	INN - Proposed INN	OLANZAPINE
D.3.9.1	CAS number	132539-06-1
D.3.9.2	Current sponsor code	Zyprexa
D.3.9.3	Other descriptive name	Olanzapin
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2,5 to 20
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	Yes
D.3.11.13.1	Other medicinal product type	Chemical, synthetic medicinal product

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

Patients with schizophrenia and related non-affective psychotic disorders, corresponding to ICD-10 diagnoses F10.5-19.5, and F20-29.

E.1.1.1

Medical condition in easily understood language

Schizophrenia and related non-affective psychotic disorders

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	13.1
E.1.2	Level	HLGT
E.1.2	Classification code	10039628
E.1.2	Term	Schizophrenia and other psychotic disorders
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

Compare the clinical effectiveness of amisulpride, aripiprazole, and olanzapine, in patients with schizophrenia and related psychotic disorders, in a head-to-head pragmatic, randomized trial funded independently of the pharmaceutical industry; and , through a translational approach, to link drug-induced changes in symptoms, neurocognitive functioning and side effects, to changes in biological substrates on neurochemical, functional and structural levels. .

E.2.2

Secondary objectives of the trial

In the randomized, head-to-head design, among the IMPs:
1. Compare the drugs with regards to cognitive functions localized in prefrontal cortex and the corresponding brain activation, change of cortical thickness, and myelin sheath regeneration.
2. Compare effects on mood symptoms and suicidal behaviour.
3. Compare akathisia by objective measurements.
4. Compare heart rate variability.
5. Compare antipsychotic-induced differential gene expression related to lipid metabolism in patients.
6. Compare inflammation markers associated with cardiovascular disease and general inflammation.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

a) Patients 18 years and more with symptoms of active psychosis as determined by a score of 4 or more on one or more of the items Delusions, Hallucinatory behavior, Grandiosity, Suspiciousness/ persecution, or Unusual thought content in the Positive and Negative Syndrome Scale (PANSS).
b) Fullfilling the diagnostic criteria for one or more of the following ICD-10 diagnoses:
F10.5, F11.5, F12.5, F13.5, F14.5, F15.5, F16.5, F17.5, F18.5, F19.5; F20-29.
c) Antipsychotic drug therapy indicated using the oral formulation of the drugs.

E.4

Principal exclusion criteria

a) Diagnosis of affective psychosis
b) Unable to comply with study protocol
c) Does not understand the language spoken at the investigation site.
d) Patients with organic psychosis due to limbic encephalitis
e) Pregnant or breast feeding women
f)Hypersensitivity to active ingredient or any of the excipients
g) Prolactin-dependent tumours
h) Use of drugs which could induce torsade de pointes
i) Phaeochromocytoma
j) Use of levodopa
k) Known risk of narrow-angle glaucoma

E.5 End points

E.5.1

Primary end point(s)

The primary end point will be differences among the treatment groups with regards to change of the PANSS positive subscale score at 12 months.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

E.5.2

Secondary end point(s)

The secondary end points will be differences among the treatment groups with regards to the following outcome measures:
The patients will be tested at baseline and thereafter at weeks 1, 3, 6; months 3,6, 9, and 12 after baseline.
The other assessment include:
5.2 Assessments at baseline
5.2.1 General Demographics, prior/ present mental/ physical illness, drug/ alcohol/ smoke.
5.2.2 Diagnostics SCID1 diagnostic interview
5.3 Repeated assessments (baseline; weeks 1,3,6; months 3,6,9,12)
5.3.1 Physical Blood pressure, Body mass index (BMI), waist and hip ratios.
5.3.2 Psychometric tools/ side effect rating scales The Positive And Negative Syndrome Scale; The revised Beliefs About Voices Questionnaire; The Calgary Depression Scale for Schizophrenia; The Clinical Global Impression Scale – Severity of illness; The Global Assessment of Functioning scale – Split version ; the Drake Scale (the alcohol and drug use scale); AUDIT/ DUDIT; The UKU Side Effect Rating Scale; Insight scale; Suicide scale; Young Mania Scale
5.3.3 Neurocognitive tests
The battery includes tests of executive functioning and attention/working memory, assessing functions localized to frontal brain regions more likely to be influenced by medication effects.
5.3.4 Laboratory
ECG; Blood: General blood screen, CRP, ALAT, ASAT, GT, Albumin, Na, K, Ca, Kreatinin, Serum lipids, glucose, C-peptide, HbA1c, Thyroid status, Prolactin, sex hormones, bone turnover markers, serum level of antipsychotic drug, inflammatory markers (cytokines IFNγ, TNFα, IL2, IL4, IL6, IL10) markers of enkothelial activation (E-selectin, ICAM-1, VCAM-1, von Willebrand factor), antibodies, such as NMDAR, VGKC and paraneoplastic antibodies. ; Genetics: DNA, RNA; Urin: Drug screen, Pregnancy test
5.4 Functional and structural MRI (Baseline and repeated)

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months

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

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

rater-blind

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

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

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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 visit by the last subject undergoing the trial.

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