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

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02580305
• Other study ID #: CTP2S1502HT6
• Status: Completed
• Phase: Phase 2
• Start date: September 2015
• Est. completion date: November 7, 2019

Study information

• Verified date: May 2023
• Source: Suven Life Sciences Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 564
• Est. completion date: November 7, 2019
• Est. primary completion date: November 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• SUVN-502
Once-daily, tablets, orally
• Placebo
Once-daily, tablets, orally
• Donepezil
Donepezil HCl (10 mg, once a day)
• Memantine
Memantine HCl (10 mg, twice a day or 28 mg extended-release, once a day).

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Suven Life Sciences Limited

Country where clinical trial is conducted

United States, 

References & Publications (3)

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-Con — View 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-bl — View 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/aggressio — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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

External 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