Piromelatine 20 mg in Participants With Mild Dementia Due to Alzheimer's Disease

NCT05267535 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: NEUP11-7
• Study Type: interventional
• Target: 225
• Locations: 2 countries
• Sites: 37

Brief Summary

Randomized efficacy and safety study of piromelatine 20 mg versus placebo in participants with mild dementia due to Alzheimer's disease (AD) who are 2:107,510,000-107,540,000 polymorphism non-carriers with the primary objective to compare the effect of piromelatine to that of placebo on the AD Assessment Scale cognitive subscale (ADAS-cog14) at Week 26 of double-blind treatment.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog 14)

  The ADAS was designed to measure the severity of the most important symptoms of AD. . It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention, and other cognitive abilities that are often referred to as the core symptoms of AD. The test comprises 11 items summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. A negative change indicates an improvement from baseline. The addition of delayed recall, number cancelation, and maze tasks - and thus turning ADAS cog into a 12 , 13 , and 14 item scale respectively - has increased the ability to detect changes in patients in the early stages of the disease .

  26 weeks

Secondary Outcomes (4)

• Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL)

  26 weeks

• ADCS-Clinical Global Impression of Change (CGIC)

  26 weeks

• Mini-Mental State Examination (MMSE)

  26 weeks

• Clinical Safety - descriptive statistics for Adverse Events

  26 weeks, 78 weeks

Study Arms (2)

Piromelatine 20 mg

EXPERIMENTAL

Piromelatine 20 mg tablets once daily taken before going to bed, preferably between 2100h and 2300h, and after food consumption.

Drug: Piromelatine 20 mg

Placebo

PLACEBO COMPARATOR

Matched placebo tablets, with identical features to the piromelatine tablets, will be used as control treatment

Drug: Placebo

Interventions

Piromelatine 20 mg DRUG

Tablets

Also known as: Neu-P11

Piromelatine 20 mg

Placebo DRUG

Tablets

Placebo

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 60 85 years (inclusive).
• Participant is an outpatient living at home or in an assisted living facility and is willing to attend all planned visits during the study.
• The participant has a study partner (who is not expected to change during the study) who will accompany the patient to the clinic, and/or be available by telephone at designated times, monitor administration of prescribed medications, control the minimum 2 hour daily light exposure requirement. The study partner must, in the opinion of the investigator, have enough contact with the participant to be able to perform the duties described above.
• Signed informed consent from the patient who has the capacity to provide informed consent as judged by the study investigator
• Signed informed consent from the study partner.
• Meets NIA AA research criteria for probable AD (McKhann, Knopman et al. 2011).
• Patient has a clearly documented history of cognitive decline over at least 12 months.
• Patient has MRI/CT scan, performed within 12 months before Screening, with findings consistent with the diagnosis of AD without any other clinically significant comorbid pathologies as detailed in Appendix 3. If MRI/CT was not performed within 12 months before Screening, it can be done during the screening period
• MMSE score of 20 26 (inclusive) at Screening and stability of MMSE - no more than three-point change on successive screening and baseline visits before randomization.
• Patient has a CDR GS of 0.5 1 (mild dementia) at Screening.
• Patients taking acetylcholinesterase inhibitors and or memantine for the treatment of AD may be enrolled if the patient has been taking such medication for at least 6 months before Visit 2 (Baseline) and is stable on any dose for the last 4 months prior to Baseline, and if the dose is not expected to change during study participation.
• Patients not receiving acetylcholinesterase inhibitors may be enrolled but must be stable off acetylcholinesterase inhibitors for at least 3 months before Baseline, and agreeable to not starting throughout the first 26 weeks of the trial.
• Patient has a negative drug screen (benzodiazepines or opiates) at Screening. Positive drug screen of BZDs, is allowed only if the use is intermittent and drug intake was 4 days or more before the visit
• Female patients must have had last natural menstruation ≥ 24 months before Screening OR be surgically sterile.
• Male patients and their female spouse/partners who are of childbearing potential must agree to use highly effective methods of contraception, consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at Screening, throughout the study and for 90 days post last dose, OR be surgically sterile.

You may not qualify if:

• Declines whole genome screening for 2:107,510,000-107,540,000 polymorphism and APOE4 genotyping.
• Patient is 2:107,510,000-107,540,000 polymorphism carrier.
• Patient has an alternative cause for dementia other than AD.
• A past or recent CT or MRI scan or report indicating any cortical infarct defined as \> 1.5 cm3; more than 2 lacunar infracts defined as ≤ 1.5 cm3; or diffuse white matter disease), Fazekas score of more than 1 on MRI or CT scan (more details Appendix 3).
• Patient has evidence of any clinically significant neurodegenerative disease, or other serious neurological disorders other than AD as detailed in Appendix 3,
• Patient has a concurrent psychiatric disorder that prevents his/her participation in the trial including but not limited to Schizophrenia, Bipolar and related disorders, Substance use disorders within the past 2 years, major depression, etc.
• Patient has a history of uncontrolled or untreated cardiovascular, endocrine, gastrointestinal, respiratory, or rheumatologic disorders within the past 5 years.
• Patient has a history of severe agitation and medically treated agitation.
• Patient has a history of serious infectious disease including:
• Neurosyphilis
• Meningitis
• Encephalitis
• Patient has a history of a primary or recurrent malignant disease that has not been in remission for \> 5 years prior to the Screening visit, with the exceptions of excised cutaneous squamous cell carcinoma in situ, basal cell carcinoma without recurrences; and history of intraductal breast cancer, cervical carcinoma in situ, or in situ prostate cancer resected over 5 years previously. (For resected in situ prostate cancer, i.e., high grade intraepithelial neoplasia, the patient must have a normal prostate specific antigen \[PSA\] prior to Screening and no increase in PSA since his resection surgery).
• Patient has severe pain that is likely to interfere with sleep (in the opinion of the investigator).
• Patient has any concomitant documented progressive disease likely to interfere with the conduct of the study, particularly:

Sponsors & Collaborators

• Neurim Pharmaceuticals Ltd.: lead
• Syneos Health: collaborator

Study Sites (37)

ATP Clinical Research

Costa Mesa, California, 92626, United States

Location

Collaborative Neuroscience Research, LLC

Long Beach, California, 90806, United States

Location

Asclepes Research Centers, P.C. Dba Alliance Research

Long Beach, California, 90807, United States

Location

Pacific Research Network, LLC

San Diego, California, 92103, United States

Location

RAA Apex Acquisition LLC DBA Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

The Mile High Research Center

Denver, Colorado, 80218, United States

Location

Linfritz Research Institute Inc.

Coral Gables, Florida, 33134, United States

Location

Finlay Medical Research Corp.

Greenacres City, Florida, 33467, United States

Location

Velocity Clinical Research, Inc

Hallandale, Florida, 33009, United States

Location

K2 Medical Research The Villages

Lady Lake, Florida, 32159, United States

Location

Verus Clinical research Corp

Miami, Florida, 33125, United States

Location

BioMed Research Institute, Inc.

Miami, Florida, 33126, United States

Location

CCM Clinical Research Group, LLC

Miami, Florida, 33133, United States

Location

Advance Medical Research Center

Miami, Florida, 33135, United States

Location

Allied Biomedical Research Institute (Clinical Trials)

Miami, Florida, 33135, United States

Location

Vitae Research Center LLC.

Miami, Florida, 33135, United States

Location

Stein Gerontological Institute, Inc.

Miami, Florida, 33137, United States

Location

Miami Dade Medical Research Institute

Miami, Florida, 33176, United States

Location

K2 Medical Research Winter Garden

Ocoee, Florida, 34761, United States

Location

Interspond, LLC,

Orlando, Florida, 32807, United States

Location

The University of South Florida Board of Trustees,

Tampa, Florida, 33613, United States

Location

Alzheimer's Research and Treatment Center

Wellington, Florida, 33414, United States

Location

Velocity Clinical Research, Inc

Meridian, Idaho, 83642, United States

Location

Ocean Medical Research

Jersey City, New Jersey, 08755,, United States

Location

Advanced Memory Research Institute of New Jersey

Toms River, New Jersey, 08755, United States

Location

Integrative Clinical Trials LLC

Brooklyn, New York, 11229, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

AMC Research, LLC

Matthews, North Carolina, 28105, United States

Location

Rhode Island mood and memory research institute

Island Park, Rhode Island, 02914, United States

Location

Neurology Clinic, P.C.

Cordova, Tennessee, 38018, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Centricity Research Halifax Multispecialty

Nova Scotia, Halifax, B3S 1N2, Canada

Location

Bluewater Clinical Research Group Inc

Sarnia, Ontario, N7T 4X3, Canada

Location

LMC Clinical Research Inc. d.b.a. Centricity Research

Toronto, Ontario, M4G 3E8, Canada

Location

OCT Research ULC (dba Okanagan Clinical Trials)

Kelowna, V1Y 1Z9, Canada

Location

Medical Arts Health Research Group

Vancouver, V7T 1C5, Canada

Location

Related Links

• A Polymorphism Cluster at the 2q12 locus May Predict Response to Piromelatine in Patients with Mild Alzheimer's Disease

MeSH Terms

Conditions

Alzheimer Disease

Interventions

N-(2-(5-methoxy-indol-3-yl)-ethyl)-4-oxo-4H-pyran-2-carboxamide

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Lon Schneider, MD

  Keck School of Medicine of USC, Los Angeles, CA

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, delayed start, double blind, parallel group, placebo controlled, multicenter study

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: March 4, 2022
• Study Start: May 12, 2022
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: June 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (32); CA (5)