Idalopirdine in Patients With Mild-moderate Alzheimer's Disease Treated With Donepezil

Study Overview
=================
Brief Summary
-----------------
To establish efficacy of Idalopirdine as adjunctive therapy to donepezil for symptomatic treatment of patients with mild-to-moderate Alzheimer's disease (AD).

Detailed Description
-----------------
The study consisted of a screening period (up to 2-week period from screening to randomization), a 24-week double-blind treatment period with placebo or idalopirdine 10 mg/day or 30 mg/day as adjunctive therapy to donepezil 10 mg/day, and a 4-week safety follow-up period following study completion or withdrawal from treatment.

Official Title
-----------------
Randomised, Double-blind, Parallel-group, Placebo-controlled, Fixed-dose Study of Idalopirdine in Patients With Mild-moderate Alzheimer's Disease Treated With Donepezil

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Idalopirdine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The patient has a knowledgeable and reliable caregiver. The patient is an outpatient. The patient has probable AD. The patient has mild to moderate AD. Stable treatment with donepezil. The patient, if a woman, must have had her last natural menstruation ≥24 months prior to baseline, OR be surgically sterile. The patient, if a man, agrees to protocol-defined use of effective contraception if his female partner is of childbearing potential, OR must have been surgically sterilised prior to the screening visit. Exclusion Criteria: The patient has evidence of any clinically significant neurodegenerative disease, or other serious neurological disorders other than AD. The patient has a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) Axis I disorder other than AD. The patient has evidence of clinically significant disease. The patient's donepezil therapy is likely to be interrupted or discontinued during the study. The patient is currently receiving memantine or has taken memantine within 2 months prior to screening. Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo adjunct to 10 mg Donepezil | Drug: Placebo<br>* Once daily, matching placebo capsules, orally<br>|
| Experimental: Idalopirdine 10 mg<br>Idalopirdine adjunct to 10 mg Donepezil | Drug: Idalopirdine<br>* Once daily, encapsulated tablets, orally<br>* Other names: Lu AE58054;|
| Experimental: Idalopirdine 30 mg<br>Idalopirdine adjunct to 10 mg Donepezil | Drug: Idalopirdine<br>* Once daily, encapsulated tablets, orally<br>* Other names: Lu AE58054;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognition | Change from baseline to Week 24 in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score. The Alzheimer's Disease Assessment Scale - Cognitive subscale (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 and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Daily Functioning | Change from baseline to Week 24 in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL23) total score. The Alzheimer's Disease Cooperative Study - Activities of Daily Living (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 and Week 24 | 
| Change in Global Impression | Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) score at Week 24. The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change 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). | Baseline and Week 24 | 
| Change in Behavioural Disturbance | Change from baseline to Week 24 in Neuropsychiatric Inventory (NPI) total score. The Neuropsychiatric Inventory 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 and Week 24 | 
| Change in Individual Behavioural Disturbance Items | Change in single NPI item scores at Week 24. The Neuropsychiatric Inventory 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 then 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]). Total score for each single NPI item ranges from 0-12 (frequency multiplied by severity), where higher scores represent worse outcome. | Baseline and Week 24 | 
| Change in NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at Baseline | Change from baseline to Week 24 in NPI anxiety item score in patients with an NPI anxiety item score of at least 2 at baseline The Neuropsychiatric Inventory 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 then 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 score for the NPI anxiety item ranges from 0-12 (frequency multiplied by severity), where a higher score represents a worse outcome. | Baseline and Week 24 | 
| Number of Participants With Clinical Improvement | Clinical response at Week 24 (based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes [change in ADAS-cog below or equal to -4, change in ADCS-ADL23 at least 0, and ADCS-CGIC below or equal to 4]) | Week 24 | 
| Number of Participants With Clinical Worsening | Clinical worsening at Week 24 (Based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes [change in ADAS-cog above or equal to 4, change in ADCS-ADL23 below 0, and ADCS-CGIC above 4]) | Week 24 | 
| Change in Cognitive Aspects of Mental Function | Change from baseline to Week 24 in Mini Mental State Examination (MMSE). The Mini Mental State Examination (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 and Week 24 | 
| Change in Health-related Quality of Life (EQ-5D) Utility Score | Change from baseline to Week 24 in EuroQol 5-dimensional (EQ-5D) utility score The EQ-5D is a patient-reported assessment that measures the patient's well-being. It consists of an utility score based on 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety) and a Visual Analogue Scale (VAS). Each descriptive item is rated on a 3-point index ranging from 1 (no problems) to 3 (extreme problems) that is used for calculating a single summary index (from 0 to 1). A higher EQ-5D score indicates a worse outcome. | Baseline and Week 24 | 
| Change in Health-related Quality of Life (EQ-5D VAS) | Change from baseline to Week 24 in EQ-5D Visual Analogue Scale (EQ-5D VAS). The EQ-5D is a patient-reported assessment that measures the patient's well-being. It consists of an utility score based on 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety) and a Visual Analogue Scale (VAS). The VAS ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). | Baseline and Week 24 |