Long-term Safety and Tolerability of Idalopirdine (Lu AE58054) as Adjunctive Treatment to Donepezil in Patients With Mild-moderate Alzheimer's Disease

Study Overview
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Brief Summary
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To evaluate the long-term safety and tolerability of idalopirdine (Lu AE58054) as adjunctive therapy to donepezil in patients with mild-moderate Alzheimer's Disease (AD).

Detailed Description
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This is an interventional, multi-national, multi-site, open-label extension study in patients with mild to moderate AD who completed the 24-week lead-in study 14861A (NCT01955161) or 14862A (NCT02006641). Patients received 28-weeks of open-label treatment with idalopirdine 60 mg/day (option to reduce to 30 mg/day) as adjunctive treatment to donepezil. Approximately 100 patients, who had completed the initial 28-week period (OLEX), were included in a 24 week open-label treatment period with memantine (OLEX-MEM) that evaluated the safety and tolerability of concomitant memantine therapy in patients who were already on a stable treatment with idalopirdine and donepezil and for whom memantine treatment was clinically indicated.

Official Title
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An Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Idalopirdine (Lu AE58054) as Adjunctive Treatment to Donepezil in Patients With Mild-moderate Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Idalopirdine 60 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: the patient has completed Visit 7 (Completion Visit) in the lead-in double-blind, placebo controlled clinical studies 14861A/NCT01955161 or 14862A/NCT02006641 For patients in the OLEX-MEM: The patient has completed Visit 6 (Week 28) of the OLEX. The patient, according to the judgement of the investigator, requires initiation of treatment with memantine as per local label/SmPC/treatment guidelines. 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 acetylcholinesterase inhibitors (AChEI). Other protocol-defined inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idalopirdine (Lu AE58054) 60 mg<br>Idalopirdine 60 mg adjunct to 10 mg donepezil. The dose of idalopirdine could be decreased from 60 mg to 30 mg if 60 mg was not well tolerated. The dose of donepezil was to be maintained throughout the study. | Drug: Idalopirdine 60 mg<br>* once daily, encapsulated tablets, orally<br>|
| Experimental: Idalopirdine 60 mg + memantine<br>Idalopirdine 60 mg as adjunct to 10 mg donepezil and memantine (patient's individualised maintenance dose, either immediate-release (IR) 20 mg/day (recommended target dose) or extended release (XR) 28 mg/day (recommended target dose). Memantine was administered to approximately 100 patients included in the OLEX-MEM. The dose of idalopirdine could be decreased from 60 mg to 30 mg if 60 mg was not well tolerated. The dose of donepezil was to be maintained throughout the study. The dose of memantine could be changed at any time throughout the study. | Drug: Idalopirdine 60 mg<br>* once daily, encapsulated tablets, orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of TEAEs in the OLEX-MEM | A TEAE is an adverse event that starts or increases in intensity after the date of Baseline III (start of OLEX-MEM). | From Baseline III (start of OLEX-MEM, Week 28) to end of OLEX-MEM (Week 52) | 
| Number of Treatment Emergent Adverse Events (TEAEs) in the OLEX | A TEAE is an adverse event that starts or increases in intensity after the date of Baseline II. | Baseline II (start of OLEX, week 0) to end of OLEX (week 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognitive Aspects of Mental Function | Change from Baseline III to Week 52 in Mini Mental State Examination (MMSE). The MMSE is an 11-item test to assess the cognitive aspects of mental function. The subtests assess orientation, memory, attention, language, and visual construction. The scores for each item is dichotomous (1 = response is correct, 0 = response is incorrect). Total score of the 11 items ranges from 0 to 30 (higher score indicates lower deficit). | Baseline III (start of OLEX-MEM, Week 28) to Week 52 | 
| Change in Cognitive Aspects of Mental Function | Change from Baseline II to Week 28 in Mini Mental State Examination (MMSE). The MMSE is an 11-item test to assess the cognitive aspects of mental function. The subtests assess orientation, memory, attention, language, and visual construction. The scores for each item is dichotomous (1 = response is correct, 0 = response is incorrect). Total score of the 11 items ranges from 0 to 30 (higher score indicates lower deficit). | Baseline II (start of OLEX, Week 0) to Week 28 | 
| Change in Cognition | Change from Baseline II to Week 28 in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score. The ADAS-cog is a 11-item neuropsychological test that assess the severity of cognitive impairment. The items determine the patient's orientation, memory, language, and praxis. Total score of the 11 items range from 0 to 70 (lower score indicates lower cognitive impairment). | Baseline II (start of OLEX, Week 0) to Week 28 | 
| Clinical Global Impression Score | Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) score at Week 28. The ADCS-CGIC is a semi-structured interview to assess clinically relevant changes in patients with AD. The items determine cognition, behavior, social and daily functioning. Severity at baseline is rated on a 7-point scale from 1 (normal, not ill at all) to 7 (among the most extremely ill patients). The clinically relevant change from baseline is rated on a 7-point scale from 1 (marked improvement) to 7 (marked worsening). | Week 28 | 
| Change in Daily Functioning | Change from Baseline II to Week 28 in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL23) total score. The ADCS-ADL23 is a 23-item clinician-rated inventory to assess activities of daily living (conducted with a caregiver or informant). Each item comprises a series of hierarchical sub-questions, ranging from the highest level of independent performance to a complete loss for each activity. Total score of the 23 items ranges from 0 to 78 (higher score indicates lower disability). | Baseline II (start of OLEX, Week 0) to Week 28 | 
| Change in Behavioural Disturbance | Change from Baseline II to Week 28 in Neuropsychiatric Inventory (NPI) total score. The NPI is a 12-item structured interview with a caregiver to assess behavioural disturbances. The NPI comprises 10 behavioural and 2 neurovegetative items. Each item consists of a screening question and several sub-questions that are rated no (not present) or yes (present). Each item is rated for frequency (a 4-point scale from 1 [occasionally] to 4 [very frequent]) and severity (a 3-point scale from 1 [mild] to 3 [marked]). The total NPI score is the frequency ratings multiplied by the severity ratings and ranges from 0 to 144 (higher score indicates worse outcome). | Baseline II (start of OLEX, Week 0) to Week 28 |