Clinical Trials Register

Summary
EudraCT Number:	2007-002780-27
Sponsor's Protocol Code Number:	GAL-ALZ-3005
National Competent Authority:	Slovenia - JAZMP
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2007-11-08
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

Slovenia - JAZMP

A.2

EudraCT number

2007-002780-27

A.3

Full title of the trial

A Randomized, Double-blind, Placebo-controlled Trial of Long-term (2-year) Treatment of Galantamine in Mild to Moderately-severe Alzheimer’s Disease

A.3.1

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

A double-blind, placebo-controlled, 2-year study of galantamine used to treat patients with Mild to Moderate Alzheimer's disease.

A.4.1

Sponsor's protocol code number

GAL-ALZ-3005

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	Janssen Cilag International NV
B.1.3.4	Country	Belgium
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	Johnson & Johnson Pharmaceutical Research and Development LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimdesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31715242166
B.5.5	Fax number	+31715242110
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	Yes
D.2.1.1.1	Trade name	REMINYL, 8mg, prolonged-release capsules, hard
D.2.1.1.2	Name of the Marketing Authorisation holder	Johnson & Johnson d.o.o.
D.2.1.2	Country which granted the Marketing Authorisation	Slovenia
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	Galantamine HBr
D.3.2	Product code	R113675
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.3.8	INN - Proposed INN	Galantamine
D.3.9.1	CAS number	1953-04-04
D.3.9.2	Current sponsor code	R113675
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	8
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	REMINYL, 16 mg, prolonged-release capsules, hard
D.2.1.1.2	Name of the Marketing Authorisation holder	Johnson & Johnson d.o.o.
D.2.1.2	Country which granted the Marketing Authorisation	Slovenia
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	Galantamine HBr
D.3.2	Product code	R113675
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.3.8	INN - Proposed INN	Galantamine
D.3.9.1	CAS number	1953-04-04
D.3.9.2	Current sponsor code	R113675
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	16
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	Yes
D.2.1.1.1	Trade name	REMINYL, 24 mg, prolonged-release capsules
D.2.1.1.2	Name of the Marketing Authorisation holder	Johnson & Johnson d.o.o.
D.2.1.2	Country which granted the Marketing Authorisation	Slovenia
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	Galantamine HBr
D.3.2	Product code	R113675
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.3.8	INN - Proposed INN	Galantamine
D.3.9.1	CAS number	1953-04-04
D.3.9.2	Current sponsor code	R113675
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	24
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

Mild to moderately severe Alzheimer's Disease

E.1.1.1

Medical condition in easily understood language

Alzheimer disease, mild to moderately-severe

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	14.0
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

Overall objective
The overall objective of this study is to evaluate the benefit-risk of long-term
(over the course of 2 years) treatment with galantamine as compared with
placebo in subjects with mild to moderately-severe AD.

Primary efficacy objective
• Compare galantamine with placebo in cognitive change from baseline
to Month 24 as measured by the MMSE score

Primary safety objective
Compare the rate of mortality between subjects randomly assigned to receive
galantamine or matching placebo over the course of 2 years.

E.2.2

Secondary objectives of the trial

Secondary efficacy objectives
• Compare galantamine with placebo in cognitive change from baseline
at Month 6 as measured by the MMSE score
• Compare galantamine with placebo in change from baseline over the
course of 2 years in activities of daily living as measured by the
Disability Assessment in Dementia (DAD)
• Compare galantamine with placebo with respect to health care
utilization over the course of 2 years as measured by the time to
change in the level of accommodation using APAS-CarB
• Compare galantamine with placebo over the course of 2 years as
measured by a retrospective estimate of caregiver time spent with the
subject over the previous 3 months using the APAS-CarB

Secondary safety objective
Compare the incidence of treatment emergent adverse events, including
serious adverse events, between subjects randomly assigned to receive
galantamine or matching placebo over the course of 2 years.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

NOTE:
A pharmacogenomic blood sample (10 mL) will be collected from subjects who give separate written informed consent for this component of the study (where local
regulations permit). Subject participation in pharmacogenomic research is optional.

E.3

Principal inclusion criteria

FULL CRITERIA IN PROTOCOL

- Outpatients (M/F) 45 - 90 years of age, inclusive
- Women must be postmenopausal (for at least 1 year ), surgically sterile, sexually abstinent or practicing an effective method of birth control
- Diagnosed with mild to moderately-severe, probable or possible AD in accordance with criteria defined by the NINCDS ADRDA or DSM-IV. Subjects presenting with AD, with or without CVD may be enrolled.
- A computed tomography or MRI of the head done since onset of symptoms leading to the diagnosis of AD. If a CT scan or MRI has not been performed from the time the cognitive symptoms appeared until the subject is screened for this study, an MRI will have to be performed for inclusion in the study.
- MMSE score of 10 to 26 inclusive, at screening
- Be living at home or in residential/nursing home
-Be living with or have regular visits from a caregiver, who will accompany the subject for scheduled visit assessments for duration of the study. The caregiver must supervise the regular administration of the study medication to the subject to improve compliance and avoid dosage errors.

- Provide contact information for 2 additional family members or friends willing to provide information about the subject. Apart from that of the caregiver, contact information be available for 1 or preferably 2 additional family members or friends, who are able and willing to provide information about the subject.
- Subjects (or legal representatives) and caregiver must sign an informed consent document
- The patient and caregiver (or legal representative) must be able to speak, read, and write in the language of the tests and complete all testing
- Willing to adhere to the prohibitions & restrictions specified in study protocol
- To participate in the optional pharmacogenomic component of this study,
subjects (or legally acceptable representative) must have signed the ICF for research indicating willingness to participate in this component of the study (where local regulations permit).

E.4

Principal exclusion criteria

FULL CRITERIA IN PROTOCOL

Neurodegenerative disorders other than AD such as Parkinson's disease, Frontotemperal Dementia or Huntington's Disease.

Conditions which may contribute to dementia.

Subjects with the co-existing medical conditions such as ongoing diagnosis of untreated epilepsy, major depression, schizophrenia, or other current clinically significant psychiatric disease, severe or uncontrolled behavioral disturbances.

Clinically significant cardiovascular disease.

Received cholinergic agents for the treatment of dementia within 2 weeks prior to screening.

History of drug or alcohol abuse within the last year.

History of severe drug allergy or hypersensitivity; including recorded hypersensitivity to cholinesterase inhibitors and its excipients, cholinergic agonists or similar agents, or bromide.

Have received an investigational drug or used an experimental medical
device within the last 30 days before the planned start of treatment.

Subjects who, in the opinion of the investigator, are otherwise unsuitable
for a study of this type.

Subjects will not be entered in any other clinical study while participating
in this study unless approval of the sponsor has been given.

Employees of the investigator/study center, with direct involvement in
the proposed study/other studies under the direction of that investigator/study center, and family members of the employees or investigator.

E.5 End points

E.5.1

Primary end point(s)

The cognitive change from baseline in MMSE score for patients treated with galantamine compared with those treated with matching placebo.

E.5.1.1

Timepoint(s) of evaluation of this end point

At Month 24

E.5.2

Secondary end point(s)

i: The cognitive change from baseline in the MMSE score

ii: The cognitive change from baseline in DAD scores

iii: The time to change
in patient accommodation measured using the APAS-CarB

E.5.2.1

Timepoint(s) of evaluation of this end point

i: At Month 6

ii: At Month 24

iiI: At protocol-specified time points during the 2 year study (ie, up to 24 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

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)

Yes

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

European Union

Russian Federation

Ukraine

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 is defined as the follow-up telephone contact one month after the last visit of the last subject.

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