E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe alzheimer's disease |
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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 |
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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 |
To determine whether:
Patients with Alzheimer's disease (AD) who continue donepezil beyond moderate to severe dementia continue to show significantly less decline on ratings of cognitive function and activities of daily living over the following 12 months than those discontinuing donepezil.
Patients with AD who change to memantine therapy in place of donepezil at the point of moderate to severe dementia show significantly smaller decline on ratings of cognitive function and activities of daily living over the following 12 months than those who receive placebo.
Patients given the combination of memantine and donepezil show additive or synergistic significant benefits on measures of activities of daily living and cognitive function after 12 months compared to those patients continuing on either drug as a single treatment. |
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E.2.2 | Secondary objectives of the trial |
Patients with AD who continue donepezil beyond the moderate to severe transition point will show a significantly smaller deterioration on ratings of non-cognitive symptoms and health related quality of life over the following 12 months than those discontinuing donepezil. Patients with AD who commence memantine therapy will show a significantly smaller deterioration over the following 12 months than those who receive placebo and patients given the combination of memantine and donepezil will show additive or synergistic significant benefits after 12 months compared to those patients continuing on either monotherapy
Treatment of patients with donepezil or memantine beyond the moderate to severe dementia is more cost-effective than placebo. The combination of memantine and donepezil is more cost-effective than either monotherapy
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients will be eligible to participate if: they meet NINCDS-ADRDA criteria for probable or possible Alzheimer’s disease.
In addition to be eligible patients will need meet the following criteria:
1) SMMSE = 5 to 13 2) Continuously prescribed donepezil for at least 3 months 3) Maintained on 10mg donepezil in previous 6 weeks. 4) No changes in prescription of any psychotropic (antipsychotic, antidepressant, benzodiazepine) medication in previous 6 weeks. 5) Prescribing clinician considers (based on NICE guidance, discussions with patient and carer and clinical judgement) that change of drug treatment (i.e. stop donepezil or introduce memantine) may be appropriate. 6) Patient is community resident and has family or professional carer or is visited on at least a daily basis by carer. 7) Patient agrees to participate (see consent above) 8) Main carer (informal or professional) consents to their own involvement and the patient’s
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E.4 | Principal exclusion criteria |
1) Patient has severe, unstable or poorly controlled medical conditions apparent from physical examination or clinical history. 2) Patient is already prescribed memantine. 3) Patient is unable to take trial medications because of contra-indications or previous adverse or allergic reactions. 4) Patient is involved in another clinical trial. 5) Clinician considers patient would not be compliant with trial medication.
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Cognitive Function measured with the standardized Standardised MMSE. Although the MMSE is less sensitive to change than other more detailed measures such as the Severe impairment Battery (SIB) within the dementia severity range under study, the MMSE has been used in so many studies that its inclusion is important to allow comparisons with earlier trial data and to increase generalisability of DOMINO’s findings.
2) Activities of Daily Living measured with the Bristol Activities of Daily Living scale (BADLS) (Bucks et al 1996). The BADLS is well validated instrument with an established average rate of deterioration of 5 points per year in AD across a wide range of functional disability |
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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 | No |
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 | No |
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) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
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 | 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 the trial is defined as the end of the interventional phase, 52 weeks after the last patient is randomised |
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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 |