SUVN-502 With Donepezil and Memantine for the Treatment of Moderate Alzheimer's Disease- Phase 2a Study

Study Overview
=================
Brief Summary
-----------------
This is a phase 2a, proof-of-concept, 26-week, double-blind, multicenter, randomized, parallel group, placebo-controlled study to compare the efficacy and safety of treatment with SUVN-502 to placebo treatment in subjects with moderate Alzheimer's disease receiving stable doses of donepezil HCl and memantine HCl.

Detailed Description
-----------------
This is a phase 2a, proof-of-concept, 26-week, double-blind, multicenter, randomized, parallel group, placebo-controlled study to compare the efficacy and safety of treatment with SUVN-502 to placebo treatment in subjects with moderate Alzheimer's disease receiving donepezil HCl (10 mg qd) and either memantine HCl (10 mg twice daily [bid]) or Namenda XR® (Extended Release, 28 mg qd) or the combination therapy, Namzaric™ The primary objective of the study is to evaluate the efficacy of a serotonin receptor subtype 6 (5-HT6) antagonist, SUVN-502, compared to placebo, as adjunct treatment in subjects with moderate Alzheimer's disease (Mini-Mental State Examination [MMSE] score of 12 to 20) currently treated with the acetylcholinesterase inhibitor, donepezil hydrochloride (HCl), and the N-methyl-D-aspartic acid (NMDA) antagonist, memantine HCl. Efficacy will be assessed by the 11-item Alzheimer's Disease Assessment Scale for Cognitive Behavior (ADAScog-11) after 26 weeks of treatment.

Official Title
-----------------
A Phase 2a Multicenter, Randomized, Double-Blind, Parallel Group, 26-Week, Placebo-Controlled Study of SUVN-502 in Subjects With Moderate Alzheimer's Disease Currently Treated With Donepezil Hydrochloride and Memantine Hydrochloride

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

Intervention / Treatment
-----------------
* Drug: SUVN-502
* Drug: Placebo
* Drug: Donepezil
* Drug: Memantine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has a diagnosis of probable Alzheimer's disease based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria at least 1 year prior to the screening visit. Has a score between 12 and 20 inclusive on the MMSE at the screening and baseline visits. Has a MRI or CT scan performed within 12 months prior to screening with findings consistent with the diagnosis of dementia due to Alzheimer's disease without any other clinically significant comorbid pathologies. Must be receiving treatment with stable doses of donepezil HCl and memantine HCl for at least 3 months prior to the screening visit Availability of an eligible and reliable caregiver Must be living in the community or an assisted living facility. Must be ambulatory or ambulatory aided (use of cane or walker). Is not pregnant or planning to become pregnant during the study. Subject (or subject's legally acceptable representative) and caregiver must sign an Informed Consent to participate in the study. Exclusion Criteria: Has a diagnosis of dementia due to other than Alzheimer's Disease Is taking cholinesterase inhibitors other than donepezil HCl or taking doses of donepezil HCl other than 10 mg Is taking doses of memantine HCl other than 10 mg bid or Namenda XR® 28 mg qd. Has uncontrolled cardiac disease or hypertension. Has clinically significant renal or hepatic impairment. Has cancer or a malignant tumor, untreated thyroid disorder or has a history of seizure disorder Is treated or likely to require treatment during the study, with any medications prohibited by the study protocol.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental: SUVN-502 Low dose (50 mg)<br>SUVN-502 Low dose adjunct to base treatment with Donepezil and Memantine | Drug: SUVN-502<br>* Once-daily, tablets, orally<br>* Other names: Masupirdine;Drug: Donepezil<br>* Donepezil HCl (10 mg, once a day)<br>* Other names: Namzaric;Drug: Memantine<br>* Memantine HCl (10 mg, twice a day or 28 mg extended-release, once a day).<br>* Other names: Namenda XR®;|
| Active Comparator: Experimental: SUVN-502 High dose (100 mg)<br>SUVN-502 High dose adjunct to base treatment with Donepezil and Memantine | Drug: SUVN-502<br>* Once-daily, tablets, orally<br>* Other names: Masupirdine;Drug: Donepezil<br>* Donepezil HCl (10 mg, once a day)<br>* Other names: Namzaric;Drug: Memantine<br>* Memantine HCl (10 mg, twice a day or 28 mg extended-release, once a day).<br>* Other names: Namenda XR®;|
| Placebo Comparator: Placebo<br>Placebo adjunct to base treatment with Donepezil and Memantine | Drug: Placebo<br>* Once-daily, tablets, orally<br>Drug: Donepezil<br>* Donepezil HCl (10 mg, once a day)<br>* Other names: Namzaric;Drug: Memantine<br>* Memantine HCl (10 mg, twice a day or 28 mg extended-release, once a day).<br>* Other names: Namenda XR®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week-26 in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) | Mean change from baseline at week 26 is assessed for ADAS-Cog11 score. The ADAS-Cog11 is a structured scale that evaluates memory, orientation, attention, reasoning, language, and constructional praxis. ADAS-Cog11 measures cognition by assessing 11 metrics impaired in AD: word recall; commands; constructional praxis; naming objects and fingers; ideational praxis; orientation; word recognition; remembering test instructions; spoken language ability; word-finding difficulty; and comprehension of spoken language. The scale ranges from 0 to 70, with higher scores indicate greater impairment. | Baseline to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week-26 in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) | Clinical Dementia Rating-Sum of Boxes (CDR-SB) - Sum of Boxes CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. | Baseline to Week 26 | 
| Change From Baseline to Week-26 in Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) | The Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory Score is a 23-item inventory. The ADCS-ADL measures both basic and instrumental activities of daily living The total ADCS-ADL score ranges from 0 to 78, with lower scores indicating greater disease severity. | Baseline to Week 26 | 
| Change From Baseline to Week-26 in Neuropsychiatric Inventory (NPI) | Neuropsychiatric Inventory (NPI) 12 item - Total Score NPI assesses psychopathology in participants with dementia and other neurologic disorders. Total score ranges from 12 to 144; higher scores indicate greater disease severity. | Baseline to Week 26 | 
| Change From Baseline to Week-26 in Change in Mini Mental State Examination (MMSE) | Change in Mini-Mental State Examination (MMSE) - Total Score Minimum Score - 0, Maximum Score - 30. Higher score means better outcome. | Baseline to Week 26 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
5-HT6, Phase 2, SUVN-502, Cognition, Donepezil, Memantine, Alzheimer's Disease, Triple Combination, Proof of Concept (POC)