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

NCT02615002 | Completed Phase 2 Results DMC

• 1 other identifier: NeuP11-AD2
• Study Type: interventional
• Target: 371
• Locations: 1 country
• Sites: 56

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).

Conditions

Alzheimer's Disease

Keywords

Cognition; mild Alzheimer's disease; Sleep

Outcome Measures

Primary Outcomes (1)

• Computerized Neuropsychological Test Battery (cNTB) Z-Scores - Change From Baseline

  The global composite score of the cNTB combines the International Shopping List Test (ISLT), One Card Learning (OCL), Identification (IDN), Detection (DET), One Back Card (OBK), Controlled Oral Word Association Test (COWAT), and the Categorical Fluency Test (CFT). For each test, a z-score relative to the study baseline is calculated. The cNTB global composite score is the mean of all z-scores from the tests listed above. The scale range is from -3 to 3. Zero Z-score means no cognitive change. A negative value means decline, while a positive value means improvement.

  26 weeks

Secondary Outcomes (8)

• Change From Baseline in Global Impression of Change (CGIC)

  13 weeks, and 26 weeks

• Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for MCI (Mild Cognitive Impairment) Patients (ADCS-MCI-ADL)

  Baseline, 13 weeks, and 26 weeks

• Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog14)

  Baseline, 13 weeks, and 26 weeks

• Safety and Tolerability - Blood Pressure (mmHg)

  Baseline, and 26 weeks

• Safety and Tolerability - Heart Rate (Bpm)

  Baseline, and 26 weeks

Other Outcomes (2)

• NeuroPsychiatric Inventory (NPI) Total Score

  Baseline, and 26 weeks

• Pittsburgh Sleep Quality Index (PSQI) - Global Component Score

  Baseline, 4 weeks, 13 weeks, 26 weeks

Study Arms (4)

Piromelatine 5 mg

EXPERIMENTAL

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

Drug: Piromelatine

Piromelatine 20 mg

EXPERIMENTAL

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

Drug: Piromelatine

Piromelatine 50 mg

EXPERIMENTAL

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

Drug: Piromelatine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Piromelatine DRUG

Also known as: Neu-P11

Piromelatine 20 mg; Piromelatine 5 mg; Piromelatine 50 mg

Placebo DRUG

Also known as: Control

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:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Neurim Pharmaceuticals Ltd.: lead

Study Sites (56)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Territory Neurology & Research Institute

Tucson, Arizona, 85704, United States

Location

Citrials Inc

Bellflower, California, 90706, United States

Location

Alliance for Research

Long Beach, California, 90807, United States

Location

Renew Behavioral Health, Inc

Long Beach, California, 90807, United States

Location

ABS Health LLC

Pomona, California, 91767, United States

Location

Anderson Clinical Research

Redlands, California, 92374, United States

Location

Pacific Research Network, Inc

San Diego, California, 92103, United States

Location

Sharp Mesa Vista Clinical research

San Diego, California, 92123, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

Research Center For Clinical Studies, Inc

Norwalk, Connecticut, 06851, United States

Location

Pioneer Clinical research

Coconut Creek, Florida, 33066, United States

Location

University of Miami

Coral Gables, Florida, 33146, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

New Life Medical Research Center

Hialeah, Florida, 33012, United States

Location

Galiz reserach

Hialeah, Florida, 33016, United States

Location

Biomed Research Institute

Miami, Florida, 33126, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

Advanced Clinical research Network

Miami, Florida, 33176, United States

Location

Medical Research Group of central Florida Inc.

Orange City, Florida, 32763, United States

Location

The Roskamp Institute, Inc

Sarasota, Florida, 34243, United States

Location

Infinity Clinical Research, LLC.

Sunrise, Florida, 33351, United States

Location

Olympian Clinical Research

Tampa, Florida, 33609, United States

Location

Rowe Neurology

Lenexa, Kansas, 66214, United States

Location

KU School of Medicine-Wichita

Wichita, Kansas, 67214, United States

Location

Lake Charles Clinical Trials, LLC

Lake Charles, Louisiana, 27604, United States

Location

Pharmasite Research INC

Baltimore, Maryland, 21208, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Precise Research Centers

Flowood, Mississippi, 39232, United States

Location

Hattiesburg Clinic, P.A.

Hattiesburg, Mississippi, 39401, United States

Location

Galen Research

Chesterfield, Missouri, 63005, United States

Location

The Neurocognitive Institute, LLC

Mount Arlington, New Jersey, 07856, United States

Location

Alzheimer's Research Corporation

Paterson, New Jersey, 08759, United States

Location

Global Medical Institutes

Princeton, New Jersey, 08540, United States

Location

Neurology Specialists of Monmouth County

West Long Branch, New Jersey, 07764, United States

Location

Dent Neurosciences Research Center, Inc

Amherst, New York, 14226, United States

Location

Integrative Clinical Trials, LLC

Brooklyn, New York, 11229, United States

Location

SPRI Clinical Trials, LLC

Brooklyn, New York, 11235, United States

Location

Manhattan Behavioral Medicine, PLLC

New York, New York, 10022, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

New Hope Clinical research

Charlotte, North Carolina, 28211, United States

Location

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

Raleigh, North Carolina, 27609, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

Red river medical research Center

Oklahoma City, Oklahoma, 73112, United States

Location

Tulsa Clinical Research, LLC.

Tulsa, Oklahoma, 74104, United States

Location

The Clinical research Center LLC

Jenkintown, Pennsylvania, 19046, United States

Location

Suburban Research Associates

Media, Pennsylvania, 19063, United States

Location

Roper St. Francis Healthcare

Charleston, South Carolina, 29401, United States

Location

Shepherd Clinical Research LLC

Lewisville, Texas, 75067, United States

Location

Radiant Research

San Antonio, Texas, 78229, United States

Location

Grayline Research Center

Wichita Falls, Texas, 76309, United States

Location

Aspen Clinical research

Orem, Utah, 84058, United States

Location

Wasatch Clinical Research LLC

Salt Lake City, Utah, 84107, United States

Location

Zain Research, Llc

Richland, Washington, 99352, United States

Location

SSM Health/Dean Medical Group

Madison, Wisconsin, 53715, United States

Location

Related Publications (1)

• 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.

  PMID: 35542997 DERIVED

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

Results Point of Contact

• Title: Tali Nir, DVM, VP Clinical and Regulatory Affairs
• Organization: Neurim Pharmaceuticals

talin@neurim.com

+972-3-7684902

Study Officials

• Lon Schneider, MD

  Keck School of Medicine of USC, Los Angeles, CA

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: November 18, 2015
• First Posted: November 25, 2015
• Study Start: November 1, 2015
• Primary Completion: June 1, 2019
• Study Completion: November 19, 2019
• Last Updated: July 5, 2024
• Results First Posted: July 5, 2024

Record last verified: 2024-07

Locations

US (56)