E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
To determine the efficacy of memantine in the treatment of Agitation in Alzheimer's dementia |
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E.2.2 | Secondary objectives of the trial |
1. To investigate the effect of Memantine on the subtypes of agitation such as verbal and physical aggression. 2. To investigate the effect of Memantine on other secondary outcome measures, namely activities of daily living, other BPSD symptoms, the need for rescue pharmacological intervention such hypnotics and antipsychotics, cognitive functioning. 3. To investigate what baseline factors predict clinical response. 4. To investigate whether there are any adverse effects of Memantine treatment in the study population.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Residential/Inpatients at recruitment with a history of at least 2 weeks behavioural disturbance 2. Alzheimer’s Disease only as per NINCDS-ADRDA Criteria (McKhann et al 1984) + Haschinski Score<=4. 3. Moderately severe to severe Alzheimer’s Disease (as determined by baseline MMSE < 19). 4. Clinically significant agitation that requires pharmacological or non pharmacological treatment. 5. Severity of agitation defined by Cohen Mansfield agitation inventory (CMAI) ≥ 45 (Cohen Mansfield 1995). 6. Age > 45.
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E.4 | Principal exclusion criteria |
1.Memantine usage in the 4 weeks prior to the start of the study. 2. On Cholinesterase inhibitor for less than 3 months and not on a stable dose. 3. Anti-psychotic, benzodiazepine or hypnotic dosage alteration in the week prior to the start of the study. 4. Antiparkinsonian medication 5. Hypersensitivity to memantine or any of the excipients in the formulation. 6. Severe renal impairment. 7. Epilepsy or history of convulsions or receiving antiepileptic medication. 8. Concomitant usage of N-methyl-D-aspartate (NMDA) antagonists such as amantadine, ketamine or dextromethorphan. 9. Recent myocardial infarction, uncompensated congestive heart failure and uncontrolled hypertension. 10. Severe, unstable or poorly controlled acute or chronic medical illness. 11. Any disability that may interfere with the patient completing the study procedure. 12. Active malignancy. 13. Any medical illness as a clear cause of agitation, including Delirium + pain. 14. Any important drug interactions: Prohibited during study and in the 14 days preceding enrollment/inclusion are: Analgesic dextromethorpan, Dopaminergics- amantadine. Warfarin due to INR prolongation.
During the study patients will be allowed to continue taking stable doses of concomitant medicines including antidepressants, antihypertensives, anti-inflammatory drugs, atypical anti-psychotics, anticoagulants, laxatives, diuretics, hypnotics and benzodiazepines (Tariot et al, 2004). Concomitant administration of anti-parkinsonian medication will be permitted but stable dose and no patients on amantadine this is to avoid difficulties with PD stability as Memantine can have benefit in PD. Cholinesterase inhibitors will not be permitted unless patients have been stable on that medication for at least 3 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in CMAI at 6 weeks at 10mg twice daily dose – primary hypothesis 6 point difference in change score in favour of memantine. Intermediate assessment points at 2, 4, and 6 weeks. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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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Completion of 12 week period by patients unless withdrawn. Patients will be followed up if they discontinue early as this is an intention to treat study. |
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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 | 3 |
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 | 0 |