Safety and Efficacy of Piromelatine in Mild Alzheimer's Disease Patients (ReCOGNITION)

NCT ID: NCT02615002

Last Updated: 2024-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 371 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2019-11-19

Brief Summary

This study is a Phase 2, randomized, placebo-controlled, dose-ranging study of piromelatine (5, 20, and 50 mg daily for 6 months) versus placebo to determine an effective dose based on efficacy (cognitive performance), safety, and tolerability in patients with mild dementia due to Alzheimer's Disease (AD).

Detailed Description

Patients with a documented history of mild dementia due to AD for at least 6 months, having a Mini-Mental State Examination (MMSE) score of 20 to 27 (inclusive) at Screening.

A score of 27 is allowed only if accompanied by a score of ≥ 12 in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) ADAS-cog11 portion of the ADAS-cog14 at screening, and a Clinical Dementia Rating Global Score (CDR-GS) of 0.5 or 1 will be recruited and further screened for eligibility. Caregiver commitment to the study is also necessary.

At Screening (Visit 1), patients will undergo neuropsychiatric assessments, psychometric testing, and general medical assessments (including medical history, pre-existing conditions, physical examination, vital signs, and ECG). If patients have not had brain imaging with findings consistent with the diagnosis of dementia due to AD in the last 12 months, a computed tomography (CT) or magnetic resonance imaging (MRI) scan will be obtained to rule out clinically significant comorbid pathologies.

Eligible patients will start a 2-week run-in period of placebo (single-blind), followed by 26 weeks of double-blind treatment comprising administration of piromelatine or placebo, for a total treatment duration of 28 weeks. During the double-blind period, patients will be enrolled in a 1.2:1:1:1 randomization ratio to the 4 trial arms (placebo [1.2], and the equal piromelatine treatment arms 5, 20, and 50 mg [1:1:1]).

Intermediate visits will be carried out at 4 weeks (Visit 3) and 13 weeks (Visit 4) after randomization. A follow-up phone call to elicit any safety concerns will be completed 2 weeks after the last dose of study medication. Patients who discontinue before Visit 5 (Week 26) will be brought back for a termination visit.

Assuming an effect size between the treatment dose and placebo of 0.35 over 26 weeks, a significant level (α) of 0.05, and power of 88%, a sample size of 143 patients for the placebo arm and 119 patients for each of the 3 piromelatine arms is calculated. Assuming a 50% screen failure rate and allowing for 15% patient withdrawal, 1150 patients should be screened to randomly assign 575 patients, of whom it is expected that 500 will complete the study.

Piromelatine (5, 20, and 50 mg tablets) and placebo will be administered orally, once daily after a meal, before habitual bedtime, preferably between 2100h and 2300h. Patients will be required to spend at least 2 hours a day exposed to daylight.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Piromelatine 5 mg

2 weeks of Placebo (run-in), followed by 26 weeks of 5 mg tablets once daily.

Group Type: EXPERIMENTAL

Piromelatine

Intervention Type: DRUG

Piromelatine 20 mg

2 weeks of Placebo (run-in), followed by 26 weeks of 20 mg tablets once daily.

Group Type: EXPERIMENTAL

Piromelatine

Intervention Type: DRUG

Piromelatine 50 mg

2 weeks of Placebo (run-in), followed by 26 weeks of 50 mg tablets once daily.

Group Type: EXPERIMENTAL

Piromelatine

Intervention Type: DRUG

Placebo

2 weeks of Placebo (run-in), followed by 26 weeks of Placebo tablets once daily.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Piromelatine

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Neu-P11; Control

Eligibility Criteria

Inclusion Criteria

• Patient and caregiver are willing to take part in the entire study
• Signed informed consent from the patient and the caregiver
• Patient has a documented history either in medical records or from an informant of cognitive decline over at least 6 months
• Patient has mild probable AD as consistent with criteria established by the National Institute on Aging and Alzheimer's Association (NIA-AA).
• CT/MRI scan with finding consisting of probable AD obtained during the last 12 months before Screening
• Patient has an MMSE score of 21-26 (inclusive) at Screening
• Patient has a Clinical Dementia Rating Global Score (CDR-GS) of 0.5-1 (mild dementia) at Screening
• Patients receiving prescribed drugs for treatment of AD including acetyl cholinesterase inhibitors [eg, donepezil, galantamine, rivastigmine] should be on a stable dose for at least 3 months before Screening
• Patient has a negative drug screen (benzodiazepines or opiates) at Screening
• Female patients must have had last natural menstruation ≥ 24 months before Screening, OR being surgically sterile
• Male patients must agree to the use of effective contraception if the female partner is of childbearing potential, OR be surgically sterile

Exclusion Criteria

• Patient has an alternative cause for dementia other than AD as determined by CT or MRI scan
• Patient has evidence of any clinically significant neurodegenerative disease
• Patient has been diagnosed with the following Axis I disorders (DSM V criteria)
• Patient has a history of uncontrolled or untreated cardiovascular, endocrine, gastrointestinal, respiratory, or rheumatologic disorders within the past 5 years
• Patient has severe pain that is likely to interfere with sleep
• Continuous use of benzodiazepines or other sedative-hypnotics during the 2 weeks before Screening
• Use of any kind of melatonin/melatonin agonist during the 2 weeks before Screening
• Patient has known or suspected hypersensitivity to exogenous melatonin or melatonin receptor agonists
• Patients with an irregular lifestyle or life pattern (eg, shift workers, patients likely to be jet lagged).

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Neurim Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lon Schneider, MD

Role: STUDY_CHAIR

Keck School of Medicine of USC, Los Angeles, CA

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Territory Neurology & Research Institute

Tucson, Arizona, United States

Citrials Inc

Bellflower, California, United States

Alliance for Research

Long Beach, California, United States

Renew Behavioral Health, Inc

Long Beach, California, United States

ABS Health LLC

Pomona, California, United States

Anderson Clinical Research

Redlands, California, United States

Pacific Research Network, Inc

San Diego, California, United States

Sharp Mesa Vista Clinical research

San Diego, California, United States

Syrentis Clinical Research

Santa Ana, California, United States

Research Center For Clinical Studies, Inc

Norwalk, Connecticut, United States

Pioneer Clinical research

Coconut Creek, Florida, United States

University of Miami

Coral Gables, Florida, United States

MD Clinical

Hallandale, Florida, United States

New Life Medical Research Center

Hialeah, Florida, United States

Galiz reserach

Hialeah, Florida, United States

Biomed Research Institute

Miami, Florida, United States

Miami Jewish Health Systems

Miami, Florida, United States

Advanced Clinical research Network

Miami, Florida, United States

Medical Research Group of central Florida Inc.

Orange City, Florida, United States

The Roskamp Institute, Inc

Sarasota, Florida, United States

Infinity Clinical Research, LLC.

Sunrise, Florida, United States

Olympian Clinical Research

Tampa, Florida, United States

Rowe Neurology

Lenexa, Kansas, United States

KU School of Medicine-Wichita

Wichita, Kansas, United States

Lake Charles Clinical Trials, LLC

Lake Charles, Louisiana, United States

Pharmasite Research INC

Baltimore, Maryland, United States

Quest Research Institute

Farmington Hills, Michigan, United States

Precise Research Centers

Flowood, Mississippi, United States

Hattiesburg Clinic, P.A.

Hattiesburg, Mississippi, United States

Galen Research

Chesterfield, Missouri, United States

The Neurocognitive Institute, LLC

Mount Arlington, New Jersey, United States

Alzheimer's Research Corporation

Paterson, New Jersey, United States

Global Medical Institutes

Princeton, New Jersey, United States

Neurology Specialists of Monmouth County

West Long Branch, New Jersey, United States

Dent Neurosciences Research Center, Inc

Amherst, New York, United States

Integrative Clinical Trials, LLC

Brooklyn, New York, United States

SPRI Clinical Trials, LLC

Brooklyn, New York, United States

Manhattan Behavioral Medicine, PLLC

New York, New York, United States

Richmond Behavioral Associates

Staten Island, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

New Hope Clinical research

Charlotte, North Carolina, United States

Richard H. Weisler, M.D., P.A. & Associates

Raleigh, North Carolina, United States

The Ohio State University

Columbus, Ohio, United States

Red river medical research Center

Oklahoma City, Oklahoma, United States

Tulsa Clinical Research, LLC.

Tulsa, Oklahoma, United States

The Clinical research Center LLC

Jenkintown, Pennsylvania, United States

Suburban Research Associates

Media, Pennsylvania, United States

Roper St. Francis Healthcare

Charleston, South Carolina, United States

Shepherd Clinical Research LLC

Lewisville, Texas, United States

Radiant Research

San Antonio, Texas, United States

Grayline Research Center

Wichita Falls, Texas, United States

Aspen Clinical research

Orem, Utah, United States

Wasatch Clinical Research LLC

Salt Lake City, Utah, United States

Zain Research, Llc

Richland, Washington, United States

SSM Health/Dean Medical Group

Madison, Wisconsin, United States

Countries

United States

References

Schneider LS, Laudon M, Nir T, Caceres J, Ianniciello G, Capulli M, Zisapel N. A Polymorphism Cluster at the 2q12 locus May Predict Response to Piromelatine in Patients with Mild Alzheimer's Disease. J Prev Alzheimers Dis. 2022;9(2):247-254. doi: 10.14283/jpad.2021.61.

Reference Type: DERIVED

PMID: 35542997 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Study Documents

Document Type: Study website

View Document

Other Identifiers

NeuP11-AD2

Identifier Type: -

Identifier Source: org_study_id