E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to moderate Alzheimer's disease in patients with depressive symptoms |
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E.1.1.1 | Medical condition in easily understood language |
Mild to moderate Alzheimer's disease in patients with depressive symptoms |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012296 |
E.1.2 | Term | Dementia of the Alzheimer's type, with depressed mood |
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 |
- Assessment of efficacy of 3 doses of S 47445 versus placebo on cognitive performance measured with the 11-item ADAS-Cog after 24 weeks of treatment
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E.2.2 | Secondary objectives of the trial |
Key secondary objective :
-Assessment of efficacy of 3 doses of S 47445 versus placebo, after 24 weeks of treatment, on activities of daily living considering the Disability Assessment for Dementia (DAD)
Secondary objectives :
- Assessment of efficacy of 3 doses of S 47445 versus placebo on cognitive performance measured by other criteria, depressive symptoms, neuropsychiatric symptoms, clinical global impression of change and functionality after 24 weeks of treatment
- Assessment of safety and tolerance of 3 doses of S 47445 after 24 and 52 weeks of treatment
- To provide S 47445 safety/tolerance and efficacy data in co-administration with donepezil after 28 weeks of treatment
- Assessment of pharmacokinetics of S47445 and/or its metabolites |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Out-patients
- Age 55-85 years
- Able to perform neuropsychological tests
- Have a responsible informant
- DSM-IV-TR criteria for Dementia of the Alzheimer’s Disease Type
- Mini mental State Examination (MMSE) = 15-24 both inclusive
- National Institute of Mental Health (NIMH) provisional criteria for depression in AD (NIMH-dAD)
- Cornell Scale for Depression in Dementia total score > or = 8
- Patients who have never been treated with AD treatments or patients who have stopped AD treatment whatever the reason
- Patients either not currently treated with an antidepressant or patients being treated with an antidepressant at the recommended dose for at least 8 weeks without clinical efficacy, who can stop this treatment according to the investigator’s opinion. |
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E.4 | Principal exclusion criteria |
- Patients not able to read or write
- Patients having participated in a study testing disease modifying therapy for AD, or in another study with administration of investigational drug or device within the previous 3 months prior to selection visit
- Depressive symptoms that, in investigator’s judgment, are clearly due to a medical condition other than AD, or are a direct result of non-mood related dementia symptoms
- History of epilepsy or solitary seizure
- Medical history of Major Depressive Disorder more than 3 years before onset of the disease, treated with antidepressive drugs or electroconvulsive therapy
- Severe or unstable disease of any type that could interfere with safety and efficacy assessments
- Alcohol abuse or drug abuse or addiction, as judged by the clinician (excluding nicotine)
- Clinically relevant lactose intolerance
- Antidepressant treatment not stopped for at least 3 weeks before inclusion
- Significant worsening of depressive symptoms or high suicidal risk according to investigator’s judgement
- For optional extension phase:
° Medically instable Chronic Obstructive Pulmonary Disease and asthma
° known hypersensitivity to donepezil hydrochloride or piperidine derivatives |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- 11-item ADAS-Cog after 24 weeks of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At W000, W004, W012, W024, W038 and W052 |
|
E.5.2 | Secondary end point(s) |
Key secondary efficacy criterion :
- Activities of Daily Living : Disability Assessment for Dementia (DAD)
Other secondary efficacy criteria :
- Cognition :
- 13-item ADAS-Cog
- Mini-Mental State Examination (MMSE)
- Depressive symptoms : Cornell Scale for Depression in Dementia (CSDD)
- Behavioural signs and symptoms : Neuropsychiatric Inventory (NPI)
- Global Clinic Assessment of Change : Alzheimer's Disease Cooperative Studies-Clinical Global Impression of Change (ADCS-CGIC)
- Functionality : Gait task (GT)
Safety criteria :
- Adverse events
- Vital signs: heart rate, body temperature, blood pressure, body weight
- Physical examination
- 12-lead ECG
- Biological laboratory parameters
- CSDD (suicide item - item 16) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- DAD : at W000, W012, W024 and W052
- 13-item ADAS-Cog : at W000, W004, W012, W024, W038 and W052
- MMSE : at W000, W012, W024 and W052
- CSDD : at W000, W004, W012, W024, W038 and W052
- NPI : at W000, W004, W012, W024 and W052
- ADCS-CGIC : W0, W24, W52
- GT : at W000, W004, W012, W024, W038 and W052
- Adverse events : all over the study
- Vital signs : blood pressure, heart rate and body temperature at W000, W004, W012, W024, W038 and W052 and body weight at W000, W012, W024, W038 and W052
- Physical examination : at W000, W004, W012, W024, W038 and W052
- 12-lead ECG : at W000, W004, W012, W024, W038 and W052
- Biological laboratory parameters : at W000, W004, W012, W024, W038 and W052
- CSDD (suicide item - item 16) at all visits |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 4 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
Brazil |
Bulgaria |
Chile |
Czech Republic |
Germany |
Hungary |
Japan |
Mexico |
Poland |
Romania |
Russian Federation |
Slovakia |
South Africa |
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
|
Last Visit Last Participant as stated in the protocol |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |