Effect of Different Doses of SAR110894 on Cognition in Patients With Mild to Moderate Alzheimer's Disease on Donepezil

Study Overview
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Brief Summary
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Primary Objective: - To demonstrate the efficacy of at least one dose of SAR110894 (H3 receptor antagonist) in comparison to placebo on cognitive performance in patients with mild to moderate Alzheimer's disease (AD) while on stable donepezil therapy Secondary Objectives: To explore the effect of SAR110894 on functional impairment, global clinical status and behavioral disturbances; To assess the safety/tolerability of SAR110894; To assess pharmacokinetic (PK) of SAR110894 and concentrations of donepezil; To explore caregiver time consumption and distress changes.

Detailed Description
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The total study duration for each patient is approximatively 36 - 38 weeks broken down as follows: Screening period: up to 4 weeks, Treatment period: 24 weeks, Follow-up period: 10 weeks.

Official Title
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A Multinational, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of the Effect on Cognitive Performance, Safety, and Tolerability of SAR110894D at the Doses of 0.5 mg, 2 mg, and 5 mg/Day for 24 Weeks in Patients With Mild to Moderate Alzheimer's Disease on Stable Donepezil Therapy

Conditions
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Dementia Alzheimer's Type

Intervention / Treatment
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* Drug: SAR110894
* Drug: placebo (for SAR110894)
* Drug: Donepezil


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with diagnosis of Alzheimer's Disease (AD) (Cannot be dementia from strokes or other causes). Patient is on stable and well-tolerated donepezil treatment at a dose of either 5 or 10 mg daily for at least 3 months prior to screening visit. Exclusion criteria: Age <55 years old. Psychotic features, agitation, or behavioral problems within the last 3 months. Patients unable to comply with ophthalmologic monitoring. Lack of consistent and reliable caregiver. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 55 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR110894 - 0.5 mg<br>SAR110894, 0.5 mg once daily along with Donepezil. | Drug: SAR110894<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>Drug: Donepezil<br>* 5 mg or 10 mg once daily continued as taken before inclusion<br>|
| Experimental: SAR110894 - 2 mg<br>SAR110894, 2 mg once daily along with Donepezil. | Drug: SAR110894<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>Drug: Donepezil<br>* 5 mg or 10 mg once daily continued as taken before inclusion<br>|
| Experimental: SAR110894 - 5 mg<br>SAR110894, 5 mg once daily along with Donepezil. | Drug: SAR110894<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>Drug: Donepezil<br>* 5 mg or 10 mg once daily continued as taken before inclusion<br>|
| Placebo Comparator: Placebo<br>Placebo (for SAR110894) once daily along with Donepezil. | Drug: placebo (for SAR110894)<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>Drug: Donepezil<br>* 5 mg or 10 mg once daily continued as taken before inclusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 24 in the standard 11-item total score from the 13-item Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog). |  | Week 4, 12, and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) global score |  | Week 4, 12, and 24 | 
| Change from baseline in each of the two remaining items of the ADAS-Cog (namely delayed word recall and concentration/distractibility) |  | Week 4, 12, and 24 | 
| Change from baseline in each of the five factors from the Cognitive Drug Research System (CDR-S) computerized assessment |  | Week 4, 12, and 24 | 
| Change from baseline in the Mini Mental State Examination (MMSE) total score |  | Week 4, 12, and 24 |