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Alzheimer's DiseasePhase 2NCT02615002

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

A Phase 2 study testing Piromelatine in people with Alzheimer's Disease, run by Neurim Pharmaceuticals Ltd. at 56 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 60 to 85 years
Conditions the study is for
Alzheimer's Disease
What is being tested?
Piromelatine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
371 participants
Where
56 sitesUnited States
Study dates
Nov 2015to 19 Nov 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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).

Trial locations and contacts

56 sites in 1 country.

56 sites in 1 country

United States56 sites

  • Dent Neurosciences Research Center, Inc

    Amherst, New York, 14226

  • Pharmasite Research INC

    Baltimore, Maryland, 21208

  • Citrials Inc

    Bellflower, California, 90706

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Integrative Clinical Trials, LLC

    Brooklyn, New York, 11229

  • SPRI Clinical Trials, LLC

    Brooklyn, New York, 11235

  • Roper St. Francis Healthcare

    Charleston, South Carolina, 29401

  • New Hope Clinical research

    Charlotte, North Carolina, 28211

  • Galen Research

    Chesterfield, Missouri, 63005

  • Pioneer Clinical research

    Coconut Creek, Florida, 33066

  • The Ohio State University

    Columbus, Ohio, 43221

  • University of Miami

    Coral Gables, Florida, 33146

  • Quest Research Institute

    Farmington Hills, Michigan, 48334

  • Precise Research Centers

    Flowood, Mississippi, 39232

  • MD Clinical

    Hallandale, Florida, 33009

  • Hattiesburg Clinic, P.A.

    Hattiesburg, Mississippi, 39401

  • New Life Medical Research Center

    Hialeah, Florida, 33012

  • Galiz reserach

    Hialeah, Florida, 33016

  • The Clinical research Center LLC

    Jenkintown, Pennsylvania, 19046

  • Lake Charles Clinical Trials, LLC

    Lake Charles, Louisiana, 27604

  • Rowe Neurology

    Lenexa, Kansas, 66214

  • Shepherd Clinical Research LLC

    Lewisville, Texas, 75067

  • Alliance for Research

    Long Beach, California, 90807

  • Renew Behavioral Health, Inc

    Long Beach, California, 90807

  • SSM Health/Dean Medical Group

    Madison, Wisconsin, 53715

  • Suburban Research Associates

    Media, Pennsylvania, 19063

  • Biomed Research Institute

    Miami, Florida, 33126

  • Miami Jewish Health Systems

    Miami, Florida, 33137

  • Advanced Clinical research Network

    Miami, Florida, 33176

  • The Neurocognitive Institute, LLC

    Mount Arlington, New Jersey, 07856

  • Manhattan Behavioral Medicine, PLLC

    New York, New York, 10022

  • Research Center For Clinical Studies, Inc

    Norwalk, Connecticut, 06851

  • Red river medical research Center

    Oklahoma City, Oklahoma, 73112

  • Medical Research Group of central Florida Inc.

    Orange City, Florida, 32763

  • Aspen Clinical research

    Orem, Utah, 84058

  • Alzheimer's Research Corporation

    Paterson, New Jersey, 08759

  • ABS Health LLC

    Pomona, California, 91767

  • Global Medical Institutes

    Princeton, New Jersey, 08540

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

    Raleigh, North Carolina, 27609

  • Anderson Clinical Research

    Redlands, California, 92374

  • Zain Research, Llc

    Richland, Washington, 99352

  • Wasatch Clinical Research LLC

    Salt Lake City, Utah, 84107

  • Radiant Research

    San Antonio, Texas, 78229

  • Pacific Research Network, Inc

    San Diego, California, 92103

  • Sharp Mesa Vista Clinical research

    San Diego, California, 92123

  • Syrentis Clinical Research

    Santa Ana, California, 92705

  • The Roskamp Institute, Inc

    Sarasota, Florida, 34243

  • Richmond Behavioral Associates

    Staten Island, New York, 10312

  • Infinity Clinical Research, LLC.

    Sunrise, Florida, 33351

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • Olympian Clinical Research

    Tampa, Florida, 33609

  • Territory Neurology & Research Institute

    Tucson, Arizona, 85704

  • Tulsa Clinical Research, LLC.

    Tulsa, Oklahoma, 74104

  • Neurology Specialists of Monmouth County

    West Long Branch, New Jersey, 07764

  • KU School of Medicine-Wichita

    Wichita, Kansas, 67214

  • Grayline Research Center

    Wichita Falls, Texas, 76309

Other trials in United States

About this study

Official title: Randomized, Double-blind, Parallel-group, Placebo-controlled, Dose Ranging Study of Piromelatine in Patients With Mild Dementia Due to Alzheimer's Disease

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).

Read the 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.

Being tested
Piromelatine, Placebo
Keywords
Cognition, mild Alzheimer's disease, Sleep
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PiromelatineDrug

    Also called Neu-P11

  • PlaceboDrug

    Also called Control

Study groups in NCT02615002
Study groupRoleWhat they receive
Piromelatine 5 mgExperimental2 weeks of Placebo (run-in), followed by 26 weeks of 5 mg tablets once daily.
Receives: Drug: Piromelatine
Piromelatine 20 mgExperimental2 weeks of Placebo (run-in), followed by 26 weeks of 20 mg tablets once daily.
Receives: Drug: Piromelatine
Piromelatine 50 mgExperimental2 weeks of Placebo (run-in), followed by 26 weeks of 50 mg tablets once daily.
Receives: Drug: Piromelatine
PlaceboPlacebo comparator2 weeks of Placebo (run-in), followed by 26 weeks of Placebo tablets once daily.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 26 weeks

Secondary outcomes (8)

  1. Change From Baseline in Global Impression of Change (CGIC)

    The Change From Baseline in Global Impression of Change (CGIC) rating is made on a 7-point Likert-type scale where the change from baseline is rated as marked improvement (1), moderate improvement (2), minimal improvement (3), no change (4), minimal worsening (5), moderate worsening (6), marked worsening (7).

    Mean values at 13 and 26 weeks are relative to baseline.

    Measured: 13 weeks, and 26 weeks

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

    ADCS-MCI-ADL is an evaluation scale with information provided by an informant/caregiver to describe the functional impairment of patients with mild cognitive impairment (MCI).

    The ADCS-ADL is a 23-item scale that includes 6 basic ADLs (BADLs) and 17 Instrumental Activities of Daily Living (IADLs) that provide a total score of 0-78, with a lower score indicating greater severity, meaning a worse outcome.

    Measured: Baseline, 13 weeks, and 26 weeks

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

    The ADAS was designed to measure the severity of the most important symptoms of AD. Its subscale, ADAS-cog, is the most popular cognitive testing instrument used in clinical trials, measuring the disturbances of memory, language, praxis, attention, and other cognitive abilities that are often referred to as the core symptoms of AD.

    ADAS-cog14 comprises 14 items summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment.

    Measured: Baseline, 13 weeks, and 26 weeks

  4. Safety and Tolerability - Blood Pressure (mmHg)

    Systolic and Diastolic Blood Pressure is followed during the study, as safety and tolerability measures.

    Changes in BP following treatment, leading to values out of the normal limits mean a worse outcome.

    Measured: Baseline, and 26 weeks

  5. Safety and Tolerability - Heart Rate (Bpm)

    Heart Rate within normal limits = 60-100 beats per minute (bpm) during the study means a good outcome in terms of safety.

    Measured: Baseline, and 26 weeks

  6. Safety and Tolerability - ECG Interval Results - QTcF (Msec)

    QT interval corrected for heart rate by Fridericia's cube root formula (QTcF). The QTc is considered normal at < 450 msec in males, and < 470 msec in females.

    Measured: Baseline, and 26 weeks

  7. Safety and Tolerability - Hematology

    Hematology (GI/L).

    1 gill (GI) = 0.118294118 liter (L). No major changes or shifts from baseline mean good safety and tolerability.

    Measured: Baseline, and 26 weeks

  8. Safety and Tolerability - Blood Chemistry (mmol/L)

    Blood Chemistry follow-up during the experiment. No major changes or shifts from baseline mean good safety and tolerability.

    Measured: Baseline, and 26 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2015 (estimated)
  2. Study startNov 2015
  3. Primary completionJun 2019
  4. Study completion19 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
371 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02615002
Sponsor's protocol ID
NeuP11-AD2
Status last verified
Jul 2024
First submitted
18 Nov 2015
Last updated
5 Jul 2024
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 35542997

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Piromelatine in people with Alzheimer's Disease, run by Neurim Pharmaceuticals Ltd. at 56 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Computerized Neuropsychological Test Battery (cNTB) Z-Scores - Change From Baseline (time frame: 26 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02615002, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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