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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: SUVN-502; Drug: Donepezil; Drug: Memantine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 564
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
    • Tucson, Arizona, United States, 85704
      • Territory Neurology & Research Institute
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Fresno, California, United States, 93710
      • Neuro-Pain Medical Center Inc
    • Fullerton, California, United States, 72835
      • Neurology Center of North Orange County
    • Laguna Hills, California, United States, 92653
      • Senior Clinical Trials, Inc.
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, LLC
    • Los Angeles, California, United States, 90095
      • Easton Center for Alzheimer's Disease Research at UCLA
    • San Diego, California, United States, 92117
      • Paradigm Research
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologists of South Connecticut
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center, Inc
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Miami, Florida, United States, 33186
      • CCM Clinical Research Group
    • Naples, Florida, United States, 34102
      • Collier Neurologic Specialists
    • Palm Beach Gardens, Florida, United States, 33410
      • Palm Beach Neurological Center
    • Pensacola, Florida, United States, 32502
      • Anchor Neuroscience
    • Pensacola, Florida, United States, 32514
      • Emerald Coast Center for Neurological Disorders
    • Port Charlotte, Florida, United States, 33952
      • Neurostudies Inc
    • Sarasota, Florida, United States, 34243
      • The Roskamp Institute, Inc.
    • Stuart, Florida, United States, 34997
      • Brain Matters Research
    • Sunrise, Florida, United States, 33351
      • Neurology Clinical Research, Inc.
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research of Florida
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
    • Tampa, Florida, United States, 33609
      • Olympian Clinical Research
    • Tampa, Florida, United States, 33613
      • University of South Florida - Byrd Alzheimer's Institute
  • Georgia
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta, LLC
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
    • Springfield, Illinois, United States, 62702
      • Southern Illinois School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health - University Hospital
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Research Center
    • Wichita, Kansas, United States, 67214
      • KU Medical Center Wichita Clinical Trial Unit
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center
  • Maine
    • Bangor, Maine, United States, 04402
      • Acadia Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Sheppard Pratt Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Clinical Research Professionals
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
    • Rahway, New Jersey, United States, 07065
      • Advanced Memory Research Institute of NJ, PC - Internal Medicine
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute
    • Toms River, New Jersey, United States, 08755
      • Biobehavioral Health
    • West Long Branch, New Jersey, United States, 07764
      • Neurology Specialists of Monmouth County
  • New York
    • Albany, New York, United States, 12208
      • Neurological Associates of Albany, PC
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials, LLC
    • Brooklyn, New York, United States, 11235
      • SPRI Clinical Trials, LLC
    • New Windsor, New York, United States, 12553
      • Mid Hudson Medical Research
    • New York, New York, United States, 10016
      • New York University
    • New York, New York, United States, 10021
      • Eastside Comprehensive Medical Center, LLC
    • New York, New York, United States, 10022
      • Manhattan Behavioral Medicine
    • Syracuse, New York, United States, 13210
      • Upstate University Hospital (SUNY Health Science Center)
    • Woodmere, New York, United States, 11598
      • Five Towns Neuroscience Research
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research
    • Charlotte, North Carolina, United States, 28270
      • Alzheimer Memory Center
    • Raleigh, North Carolina, United States, 27609
      • Richard Weisler, MD, PA
  • Ohio
    • Canton, Ohio, United States, 44718
      • Ohio Clinical Research Partners, LLC
    • Centerville, Ohio, United States, 45459
      • Valley Medical Research
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
    • Tulsa, Oklahoma, United States, 74104
      • Tulsa Clinical Research, LLC
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network
    • Plains, Pennsylvania, United States, 18705
      • Northeastern Pennsylvania Memory and Alzheimers Center
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis Healthcare
  • Texas
    • Fort Worth, Texas, United States, 76107
      • University of North Texas Health Science Center
    • Lewisville, Texas, United States, 75067
      • Shepherd Healthcare
    • San Antonio, Texas, United States, 78229
      • Radiant Research, Inc.
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research
    • Salt Lake City, Utah, United States, 84108
      • Center for Alzheimer's Care, Imaging and Research
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • Independent Psychiatric Consultants, SC, dba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Suven Life Sciences Limited

Publications and helpful links

General Publications

• Nirogi R, Jayarajan P, Benade V, Shinde A, Goyal VK, Jetta S, Ravula J, Abraham R, Grandhi VR, Subramanian R, Pandey SK, Badange RK, Mohammed AR, Jasti V, Ballard C, Cummings J. Potential beneficial effects of masupirdine (SUVN-502) on agitation/aggression and psychosis in patients with moderate Alzheimer's disease: Exploratory post hoc analyses. Int J Geriatr Psychiatry. 2022 Oct;37(10):10.1002/gps.5813. doi: 10.1002/gps.5813.
• Nirogi R, Ieni J, Goyal VK, Ravula J, Jetta S, Shinde A, Jayarajan P, Benade V, Palacharla VRC, Dogiparti DK, Jasti V, Atri A, Cummings J. Effect of masupirdine (SUVN-502) on cognition in patients with moderate Alzheimer's disease: A randomized, double-blind, phase 2, proof-of-concept study. Alzheimers Dement (N Y). 2022 Jun 1;8(1):e12307. doi: 10.1002/trc2.12307. eCollection 2022.
• Nirogi R, Goyal VK, Benade V, Subramanian R, Ravula J, Jetta S, Shinde A, Pandey SK, Jayarajan P, Jasti V, Cummings J. Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study. Neurol Ther. 2022 Dec;11(4):1583-1594. doi: 10.1007/s40120-022-00390-4. Epub 2022 Jul 31.

Helpful Links

• Effect of Age, Cognitive Impairment Severity, and Duration of Disease on Efficacy of Masupirdine in Moderate Alzheimer's Disease Patients: A Post Hoc Analysis of a Phase-2 Randomized Placebo Controlled Study Results

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): November 5, 2019
• Study Completion (Actual): November 7, 2019

Study Registration Dates

• First Submitted: October 17, 2015
• First Submitted That Met QC Criteria: October 17, 2015
• First Posted (Estimated): October 20, 2015

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Cognition; Donepezil; SUVN-502; Phase 2; Memantine; 5-HT6; Triple Combination; Proof of Concept (POC)
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Nootropic Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Cholinesterase Inhibitors; Donepezil; Memantine; 1-((2-bromophenyl)sulfonyl)-5-methoxy-3-((4-methyl-1-piperazinyl)methyl)-1H-indole dimesylate monohydrate
• Other Study ID Numbers: CTP2S1502HT6