E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to moderately severe Alzheimer's Disease |
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E.1.1.1 | Medical condition in easily understood language |
Alzheimer disease, mild to moderately-severe |
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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 |
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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.
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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. |
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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. |
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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). |
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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. |
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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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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
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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) |
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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 | Yes |
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 | No |
E.7.1.3.1 | Other trial type description | |
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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 | No |
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 |
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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
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The end of trial is defined as the follow-up telephone contact one month after the last visit of the last subject. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |