Clinical trial NCT02580305: SUVN-502 With Donepezil and Memantine for the Treatment of Moderate Alzheimer's Disease- Phase 2a Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: SUVN-502
5-HT6
Phase 2
Cognition
Donepezil
Memantine
Alzheimer's Disease
Triple Combination
Proof of Concept (POC)
Lead sponsor: Suven Life Sciences Limited
Sponsor class: INDUSTRY
First posted: 2015-10-20
Enrollment: 564
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline to Week-26 in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11)
timeFrame: Baseline to Week 26
Secondary outcomes:
measure: Change From Baseline to Week-26 in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)
timeFrame: Baseline to Week 26
measure: Change From Baseline to Week-26 in Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL)
timeFrame: Baseline to Week 26
measure: Change From Baseline to Week-26 in Neuropsychiatric Inventory (NPI)
timeFrame: Baseline to Week 26
measure: Change From Baseline to Week-26 in Change in Mini Mental State Examination (MMSE)
timeFrame: Baseline to Week 26
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Tucson
country: United States
facility: Territory Neurology & Research Institute
state: Arizona
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Fresno
country: United States
facility: Neuro-Pain Medical Center Inc
state: California
city: Fullerton
country: United States
facility: Neurology Center of North Orange County
state: California
city: Laguna Hills
country: United States
facility: Senior Clinical Trials, Inc.
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Los Angeles
country: United States
facility: Easton Center for Alzheimer's Disease Research at UCLA
state: California
city: San Diego
country: United States
facility: Paradigm Research
state: California
city: Fairfield
country: United States
facility: Associated Neurologists of South Connecticut
state: Connecticut
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center, Inc
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Miami
country: United States
facility: CCM Clinical Research Group
state: Florida
city: Naples
country: United States
facility: Collier Neurologic Specialists
state: Florida
city: Palm Beach Gardens
country: United States
facility: Palm Beach Neurological Center
state: Florida
city: Pensacola
country: United States
facility: Anchor Neuroscience
state: Florida
city: Pensacola
country: United States
facility: Emerald Coast Center for Neurological Disorders
state: Florida
city: Port Charlotte
country: United States
facility: Neurostudies Inc
state: Florida
city: Sarasota
country: United States
facility: The Roskamp Institute, Inc.
state: Florida
city: Stuart
country: United States
facility: Brain Matters Research
state: Florida
city: Sunrise
country: United States
facility: Neurology Clinical Research, Inc.
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Tampa
country: United States
facility: Olympian Clinical Research
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: Tampa
country: United States
facility: University of South Florida - Byrd Alzheimer's Institute
state: Florida
city: Decatur
country: United States
facility: iResearch Atlanta, LLC
state: Georgia
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health - University Hospital
state: Indiana
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center
state: Kansas
city: Wichita
country: United States
facility: KU Medical Center Wichita Clinical Trial Unit
state: Kansas
city: Lexington
country: United States
facility: University Of Kentucky
state: Kentucky
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
city: Bangor
country: United States
facility: Acadia Hospital
state: Maine
city: Baltimore
country: United States
facility: Sheppard Pratt Health System
state: Maryland
city: Saint Louis
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Princeton
country: United States
facility: Princeton Medical Institute
state: New Jersey
city: Rahway
country: United States
facility: Advanced Memory Research Institute of NJ, PC - Internal Medicine
state: New Jersey
city: Toms River
country: United States
facility: Advanced Memory Research Institute
state: New Jersey
city: Toms River
country: United States
facility: Biobehavioral Health
state: New Jersey
city: West Long Branch
country: United States
facility: Neurology Specialists of Monmouth County
state: New Jersey
city: Albany
country: United States
facility: Neurological Associates of Albany, PC
state: New York
city: Brooklyn
country: United States
facility: Integrative Clinical Trials, LLC
state: New York
city: Brooklyn
country: United States
facility: SPRI Clinical Trials, LLC
state: New York
city: New Windsor
country: United States
facility: Mid Hudson Medical Research
state: New York
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Eastside Comprehensive Medical Center, LLC
state: New York
city: New York
country: United States
facility: Manhattan Behavioral Medicine
state: New York
city: Syracuse
country: United States
facility: Upstate University Hospital (SUNY Health Science Center)
state: New York
city: Woodmere
country: United States
facility: Five Towns Neuroscience Research
state: New York
city: Charlotte
country: United States
facility: New Hope Clinical Research
state: North Carolina
city: Charlotte
country: United States
facility: Alzheimer Memory Center
state: North Carolina
city: Raleigh
country: United States
facility: Richard Weisler, MD, PA
state: North Carolina
city: Canton
country: United States
facility: Ohio Clinical Research Partners, LLC
state: Ohio
city: Centerville
country: United States
facility: Valley Medical Research
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Clinical Research, LLC
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Plains
country: United States
facility: Northeastern Pennsylvania Memory and Alzheimers Center
state: Pennsylvania
city: Charleston
country: United States
facility: Roper St. Francis Healthcare
state: South Carolina
city: Fort Worth
country: United States
facility: University of North Texas Health Science Center
state: Texas
city: Lewisville
country: United States
facility: Shepherd Healthcare
state: Texas
city: San Antonio
country: United States
facility: Radiant Research, Inc.
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research
state: Utah
city: Salt Lake City
country: United States
facility: Center for Alzheimer's Care, Imaging and Research
state: Utah
city: Waukesha
country: United States
facility: Independent Psychiatric Consultants, SC, dba
state: Wisconsin
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.