Clinical Trials Register

Summary
EudraCT Number:	2015-005438-24
Sponsor's Protocol Code Number:	1346.23
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-05-18
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

Greece - EOF

A.2

EudraCT number

2015-005438-24

A.3

Full title of the trial

A multi-centre, double-blind, parallel-group, randomised controlled study to investigate efficacy and safety of orally administered BI 425809 during a 12-week treatment period compared to placebo in patients with cognitive impairment due to Alzheimer¿s Disease.

Πολυκεντρική, διπλά τυφλή, παράλληλων ομάδων, τυχαιοποιημένη, ελεγχόμενη μελέτη για τη διερεύνηση της αποτελεσματικότητας και της ασφάλειας του από του στόματος χορηγούμενου ΒΙ 425809 κατά τη διάρκεια περιόδου θεραπείας 12 εβδομάδων σε σύγκριση με το εικονικό φάρμακο σε ασθενείς με γνωστική δυσλειτουργία λόγω της Νόσου Alzheimer.

A.3.1

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

BI 425809 in patients with cognitive impairment due to Alzheimer's Disease.

BI 425809 σε ασθενείς με γνωστική δυσλειτουργία λόγω της νόσου Alzheimer

A.4.1

Sponsor's protocol code number

1346.23

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	Boehringer Ingelheim Ellas AE
B.1.3.4	Country	Greece
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Boehringer Ingelheim Ellas AE
B.4.2	Country	Greece
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Boehringer Ingelheim Pharma GmbH & Co. KG
B.5.2	Functional name of contact point	QRPE PSC CT Information Disclosure
B.5.3	Address:
B.5.3.1	Street Address	Binger Strasse 173
B.5.3.2	Town/ city	Ingelheim am Rhein
B.5.3.3	Post code	55216
B.5.3.4	Country	Germany
B.5.4	Telephone number	+18002430127
B.5.5	Fax number	+18008217119
B.5.6	E-mail	clintriage.rdg@boehringer-ingelheim.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	BI 425809/5 mg
D.3.2	Product code	BI 425809
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	not available
D.3.9.2	Current sponsor code	BI 425809
D.3.9.3	Other descriptive name	BI 425809
D.3.9.4	EV Substance Code	SUB130377
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	5
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	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	BI 425809/25 mg
D.3.2	Product code	BI 425809
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	not available
D.3.9.2	Current sponsor code	BI 425809
D.3.9.3	Other descriptive name	BI 425809
D.3.9.4	EV Substance Code	SUB130377
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	25
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: 3
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	BI 425809/1 mg
D.3.2	Product code	BI 425809
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	not available
D.3.9.2	Current sponsor code	BI 425809
D.3.9.3	Other descriptive name	BI 425809
D.3.9.4	EV Substance Code	SUB130377
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	1
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	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
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

Cognitive impairment due to Alzheimer's Disease

Γνωστική δυσλειτουργία λόγω της Νόσου Alzheimer

E.1.1.1

Medical condition in easily understood language

Cognitive impairment due to Alzheimer's Disease

Γνωστική δυσλειτουργία λόγω της Νόσου Alzheimer

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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	10012271
E.1.2	Term	Dementia Alzheimer's type
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10001896
E.1.2	Term	Alzheimer's disease
E.1.2	System Organ Class	10029205 - Nervous system 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

To assess safety, tolerability and efficacy of different doses of BI 425809 compared to placebo in treatment of cognitive impairment due to Alzheimer¿s Disease

Η αξιολόγηση της ασφάλειας, ανεκτικότητας και αποτελεσματικότητας διαφορετικών δόσεων ΒΙ 425809 σε σύγκριση με το εικονικό φάρμακο στη θεραπεία της γνωστικής δυσλειτουργίας λόγω της νόσου του Alzheimer

E.2.2

Secondary objectives of the trial

Not applicable

Δεν εφαρμόζεται

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Patients with early signs of dementia of Alzheimer Type
- Male and female patients with an age of at least 55 years
- Concomitant use of AChEIs is allowed but not required. Patients who are currently taking AChEIs are eligible as long as they have been using a stable dose for at least 3 months prior to screening and no change is foreseen for the duration of the study. This dose must be consistent with the product label in the concerned country. Patients who are not currently taking AChEIs but have taken them in the past are also eligible if AChEIs were stopped at least 3 months prior to screening.

- Patients must have at least 6 years of formal education and fluency in the test language as verbally confirmed by the patient and documented by the study investigator.
- Patients must have a reliable study partner (per investigator judgement, for instance a family member, partner etc., guardian or, if applicable, a legal representative)

- Ασθενείς με πρώιμα σημεία άνοιας τύπου Alzheimer
- Άνδρες και γυναίκες ασθενείς ηλικίας τουλάχιστον 55 ετών
- Η ταυτόχρονη χρήση AChEIs επιτρέπεται αλλά δεν απαιτείται. Οι ασθενείς οι οποίοι λαμβάνουν επί του παρόντος AChEIs είναι κατάλληλοι υπό την προϋπόθεση ότι χρησιμοποιούν σταθερή δόση για τουλάχιστον 3 μήνες πριν τον έλεγχο διαλογής και δεν προβλέπεται αλλαγή για το χρόνο που θα διαρκέσει η μελέτη. Η δόση αυτή θα πρέπει να συμφωνεί με τα αναγραφόμενα στην ετικέτα στην υπό εξέταση χώρα. Ασθενείς οι οποίοι δεν λαμβάνουν επί του παρόντος AChEIs αλλά λάμβαναν στο παρελθόν είναι επίσης κατάλληλοι εάν η χορήγηση των AChEIs διακόπηκε τουλάχιστον 3 μήνες πριν τον έλεγχο διαλογής.
- Οι ασθενείς θα πρέπει να έχουν λάβει τουλάχιστον 6 έτη τυπικής εκπαίδευσης και να έχουν ευχέρεια στη γλώσσα στην οποία εξετάζονται η οποία θα πρέπει να είναι προφορικά επιβεβαιωμένη από τον ασθενή και τεκμηριωμένη από τον ερευνητή της μελέτης.
- Οι ασθενείς θα πρέπει να έχουν έναν αξιόπιστο βοηθό για τη μελέτη (κατά την κρίση του ερευνητή, για παράδειγμα κάποιο μέλος της οικογένειας, σύντροφο κτλ, κηδεμόνα ή, εάν εφαρμόζεται, έναν νόμιμο εκπρόσωπο)

E.4

Principal exclusion criteria

- Cognitive impairment or dementia with any etiology other than dementia of Alzheimer Type
- Substantial concomitant cerebrovascular disease (defined by a history of a stroke / intracranial haemorrhagia) temporally related to the onset of worsening of cognitive impairment per investigator judgement
- Medical history or diagnosis of any of symptomatic and unstable/uncontrolled conditions per investigator judgement
- Patients receiving prescribed drugs for treatment of dementia of Alzheimer Type (other than Acetylcholine Esterase Inhibitors) at screening or within 3 months prior to screening
- Any other psychiatric disorders such as schizophrenia, or mental retardation
- Previous participation in investigational drug studies of mild cognitive impairment/DAT within three months prior to screening. Having received active treatment in any other study targeting disease modification of AD like Aß immunization and tau therapies. Previous participation in studies with non-prescription medications, vitamins or other nutritional formulations is allowed.
- Clinically significant uncompensated hearing loss in the judgment of the investigator. Use of hearing aids is allowed.

- Γνωστική δυσλειτουργία ή άνοια οποιασδήποτε αιτιολογίας εκτός της άνοιας τύπου Alzheimer
- Σημαντική συνυπάρχουσα καρδιαγγειακή νόσος (η οποία προσδιορίζεται από ιστορικό εγκεφαλικού επεισοδίου / ενδοκρανιακής αιμορραγίας) χρονικά σχετιζόμενη με την εμφάνιση ή την επιδείνωση της γνωστικής βλάβης κατά την κρίση του ερευνητή.
- Ιατρικό ιστορικό ή διάγνωση οποιωνδήποτε συμπτωματικών και ασταθών/μη ελεγχόμενων καταστάσεων κατά την κρίση του ερευνητή
- Ασθενείς που λαμβάνουν συνταγογραφούμενα φάρμακα για τη θεραπεία της άνοιας τύπου Alzheimer (διαφορετικά από τους αναστολείς της εστεράσης ακετυλοχολίνης) κατά τη διαλογή ή εντός 3 μηνών πριν τον έλεγχο διαλογής
- Οποιαδήποτε άλλη ψυχιατρική διαταραχή όπως σφιζοφρένια ή διανοητική καθυστέρηση
- Προηγούμενη συμμετοχή σε μελέτες ερευνητικών φαρμάκων για την ήπια γνωστική δυσλειτουργία/ άνοια Τύπου Alzheimer (DAT) εντός των τελευταίων τριών μηνών πριν τη διαλογή. Λήψη ενεργού θεραπείας σε οποιαδήποτε άλλη μελέτη η οποία έχει στόχο την τροποποίηση της νόσου Alzheimer όπως Αβ ανοσοποίηση και tau θεραπείες. Προηγούμενη συμμετοχή σε μελέτες μη συνταγογραφούμενων φαρμάκων, βιταμινών ή άλλων θρεπτικών σκευασμάτων επιτρέπεται.
- Κλινικά σημαντική μη αντιρροπιστική (uncompensated) απώλεια ακοής κατά την κρίση του ερευνητή. Επιτρέπεται η χρήση ακουστικών βοηθημάτων.

E.5 End points

E.5.1

Primary end point(s)

1: The change from baseline in ADAS-Cog13 (Alzheimer's Disease Assessment Scale - cognitive 13 item subscale) total score

1: Αλλαγή από την αρχική τιμή της συνολικής βαθμολογίας ADAS-Cog13 (Κλίμακα Αξιολόγησης της Νόσου Alzheimer – γνωστική υπό-κλίμακα 13 στοιχείων)

E.5.1.1

Timepoint(s) of evaluation of this end point

1: 12 weeks

1: 12 εβδομάδες

E.5.2

Secondary end point(s)

1: Change from baseline in the ADCS-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living) score

2: Change from baseline CDR-SB (Clinical Dementia Rating / Sum of Boxes)

1: Αλλαγή από την αρχική τιμή της βαθμολογίας ADCS-ADL (Συνεργατική Μελέτη για τη Νόσο Alzheimer / Δραστηριότητες της Καθημερινής Ζωής)

2: Αλλαγή από την αρχική τιμή της βαθμολογίας CDR-SB (Κλίμακα Κλινικής Ταξινόμησης της Άνοιας – Άθροισμα Κουτιών/Πεδίων)

E.5.2.1

Timepoint(s) of evaluation of this end point

1: 12 weeks

2: 12 weeks

1: 12 εβδομάδες

2: 12 εβδομάδες

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

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

Yes

E.6.10

Pharmacogenetic

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)

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Austria

Canada

Finland

France

Germany

Greece

Hungary

Italy

Japan

Norway

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

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

LVLS

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

Number of subjects for this age range:

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:

293

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

292

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

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.4.2

For a multinational trial

F.4.2.1

In the EEA

472

F.4.2.2

In the whole clinical trial

750

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

Καμία

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

2016-06-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-10-11

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