E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
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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 |
Open-label treatment period (initial 28 weeks): To evaluate the long-term safety and tolerability of idalopirdine as adjunctive therapy to donepezil in patients with mild-moderate AD.
Open-label treatment period with memantine (sub-study): To evaluate the safety and tolerability of concomitant treatment with idalopirdine, memantine and donepezil in patients with AD. |
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E.2.2 | Secondary objectives of the trial |
Open-label treatment period (initial 28 weeks): To evaluate the disease development during long-term treatment with idalopirdine as adjunctive therapy to donepezil.
Open-label treatment period with memantine (sub-study): To evaluate the disease development during concomitant treatment with idalopirdine, memantine and donepezil in patients with AD. |
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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 |
Open-label treatment period with memantine |
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E.3 | Principal inclusion criteria |
Open-label treatment period (initial 28 weeks):
• The patient has completed Visit 7 (Completion Visit) in the lead-in double-blind, placebo controlled clinical studies 14861A or 14862A.
Open-label treatment period with memantine (sub-study):
Major inclusion criteria at Baseline III:
* The patient has completed Visit 6 [(i.e., the open-label treatment period (initial 28-week period)].
* The patient has a MMSE score at Visit 6 not greater than 19 in accordance with the memantine label/summary of product characteristics (SmPC).
* The patient, according to the judgement of the investigator, requires initiation of
treatment with memantine as per locallabei/SmPC/treatment guidelines. |
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E.4 | Principal exclusion criteria |
• The patient has a moderate or severe ongoing adverse event from the lead-in study considered a potential safety risk by the investigator.
• The patient has experienced seizures before Completion Visit in the lead-in study.
• The patient has evidence of clinically significant disease.
• The patient's donepezil treatment is likely to be interrupted or discontinued during the study.
• The patient is receiving therapy with another AChEI or memantine.
Open-label treatment period with memantine (sub-study):
Major exclusion criteria at Baseline III:
* The patient exhibits an increase in MMSE score by 3 points or more at Visit 6 from Baseline II.
* The patient has a moderate or severe on-going adverse event from the open-label treatment period (initial 28-week period) considered a potential safety risk by the investigator.
* The patient has a previous history of testing positive for hepatitis B surface antigen (HBsAg), or hepatitis C virus / antibodies (anti-HCV) AND had abnormal ALT, AST or bilirubin during the open-label treatment period (initial 28-week period).
* The patient has tested positive for hepatitis B surface antigen (HBsAg), or hepatitis C virus /antibodies (anti-HCV) for the frrst time within the last 6 months prior to the Visit 6 in the open-label treatment period (initial 28-week period).
* The patient has one or more clinical laboratory test values outside the reference
range, based on the latest available blood and urine sample results during the open-label treatment period (initial 28-week period), that are of potential risk to the patient's safety, or the patient has according to the latest available blood sample:
- a serum creatinine value >1.5 times the upper limit of the reference range, or
- a serum total bilirubin value >1.5 times the upper limit of the reference range, or
- a serum alanine aminotransferase (AL T) or aspartate aminotransferase (AST)
value >2 times the upper limit ofthe reference range. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Safety: Number of adverse events
• Tolerability: Number of withdrawals |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 28 weeks and a 4-week safety follow-up |
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E.5.2 | Secondary end point(s) |
• Change in cognition: Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score
• Change in global impression: Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) score
• Change in functioning: Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL23) total score
• Change in behavioural disturbance: Change in Neuropsychiatric Inventory (NPI) total score
• Change in cognitive aspects of mental function: Change in Mini Mental State Examination (MMSE)
• Risk of Suicidality Using C-SSRS Scores: Columbia Suicide Severity Rating Scale (C-SSRS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline and Week 28 for all, except for Risk of Suicidality which is up to week 28. |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 108 |
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 |
Argentina |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Croatia |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Germany |
Hungary |
Ireland |
Israel |
Italy |
Korea, Republic of |
Lithuania |
Poland |
Portugal |
Romania |
South Africa |
Spain |
Taiwan |
Ukraine |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 28 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 28 |