| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Mild to moderately severe Alzheimer's Disease |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001896 |
| E.1.2 | Term | Alzheimer's disease |
|
| E.1.3 | Condition being studied is a rare disease | No |
| 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 (men or women), 45 to 90 years of age, inclusive
• Women must be postmenopausal (for at least 1 year), surgically sterile, sexually abstinent or if sexually active be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study. Women of childbearing potential must have a negative serum β-hCG or urine pregnancy test at screening and at times as deemed appropriate by
the investigator.
• Diagnosed with mild to moderately-severe, probable or possible AD established in accordance with the criteria defined by the NINCDS-ADRDA or DSM-IV. Subjects presenting with AD, with or without CVD may be enrolled.
• A computed tomography (CT) or magnetic resonance imaging (MRI) of the head done since the 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, it will have to be performed for inclusion in the study.
• An MMSE score of 10 to 26 inclusive, at screening (Visit 1)
• Be living at home or in residential/nursing homes
• Be living with or have regular and frequent visits from a responsible caregiver. The caregiver must supervise the regular administration of the study medication to the subject to improve compliance and avoid dosage errors, be willing to provide information about the subject, and prepared to accompany the subject for scheduled visit assessments for the full 2-year duration of the study. Note: There may be more than 1 caregiver. However, the same caregiver should assess the subject throughout the study whenever possible. Because of the long-term nature of the study, it is highly desirable that, 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 their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study in accordance with the requirements of the ethical review committee
• Informed consent must also be given by the caregiver for their own participation in the study for the full 2-year period
• The subject and caregiver (or their legally acceptable representative) must be able to speak, read, and write in the language of the tests being administered and must be able to complete all testing
• To participate in the optional pharmacogenomic component of this study, subjects (or their legally acceptable representative) must have signed the informed consent form (ICF) for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to consent for this component does not exclude a subject from participation in the clinical study.
• Willing to adhere to the prohibitions and restrictions specified in this
protocol |
|
| 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 primary efficacy endpoint will be the change from baseline in the MMSE score at Month 24.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Phase IIIb [Long-term (2-year) Treatment] |
|
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 78 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 7 |
| 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 | 7 |
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