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Alzheimer's DiseasePhase 2/3NCT05267535

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

A Phase 2/3 study testing Piromelatine 20 mg in people with Alzheimer's Disease, run by Neurim Pharmaceuticals Ltd. at 37 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… 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 20 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
216 participants
Where
37 sitesin 2 countries
Study dates
15 Jun 2022to 12 Dec 2024
Phase
Phase 2/3
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

  • 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).
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  • 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.
  • Patients who are taking medications for non excluded concurrent medical conditions should be on a stable dose for at least 4 weeks before Screening. Patients taking allowed antidepressants (see Section 12.9) should be on a stable dose for at least 3 months before Screening and throughout the study
  • Patient has ability and commitment to spend at least 2 hours per day exposed to daylight (preferably outside but can be next to a window if weather or personal situation does not permit).
  • Participant and study partner have the ability to read and write in English or Spanish and have hearing, vision, and physical abilities adequate to perform assessments (corrective aids allowed).
  • Participant and study partner are fully vaccinated for COVID 19 including booster doses as indicated (6 months post second dose). Having been diagnosed with COVID 19 after completing the initial full Covid vaccine would meet the requirements for a booster shot

Who cannot join

  • 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.
Show all 38Show fewer
  • 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:
  • Liver disease with aspartate aminotransferase (AST), alanine aminotransferase (ALT) or gamma glutamyltransferase (GGT) > 3 times the upper limits of normal (ULN)
  • Total bilirubin > 3 times the ULN
  • Mean corpuscular volume > 95 µ3 if due to chronic alcoholism
  • Renal failure with creatinine < 30 ml / min
  • Patients that are taking prohibited medications according to Appendix 2 See also section 12.9.
  • Continuous use of benzodiazepines or other sedative hypnotics during the 2 weeks before Screening (see Section 12.9).
  • Patient has a history of chronic use (more than 3 months of continuous use) and abuse of benzodiazepines or other sedative hypnotics.
  • Use of any kind of melatonin/melatonin agonist during the 2 weeks before Screening (see Section 12.9).
  • Patient has known or suspected hypersensitivity to exogenous melatonin or melatonin receptor agonists.
  • Patient has clinically significant abnormal laboratory findings that have not been approved by the study safety officer.
  • Patient has persistent bradycardia (heart beat < 50 bpm) or tachycardia (heart beat > 100 bpm).
  • Patient has atrioventricular block (type II/Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or a marked prolongation of QTc interval (repeated demonstration in ECGs of QTc interval > 450 msec for males and > 470 msec for females using Fridericia's formula: QTc = QT/cube root of RR).
  • Patient has other serious diseases that could interfere with patient assessment, in the opinion of the investigator.
  • Patient has untreated B12 and/or folic acid deficiency.
  • Patient has participated in a clinical trial with any investigational agent within 3 months before Screening. Participants in any former monoclonal antibody clinical trial for AD are not eligible until 6 months after the last visit of the previous study. Patients who have received active vaccine for AD in the past will be excluded.
  • Patient with a body mass index (BMI) above 35 or below 18.
  • Lifestyle exclusions:
  • Patients unwilling to limit alcohol intake to less than 30 g of pure alcohol per day (see Appendix 1) and to abstain after 2000h throughout the study
  • Patients unwilling to be exposed to at least 2 hours of daylight each day
  • Divergence from the accepted level of study medication compliance (70% 130% of expected consumption) as verified at Visit 2 (see Section 12.10)
  • Patients consuming more than 7 cups of tea or coffee (or equivalent amount of caffeine [650 mg] in other caffeinated beverages) per day
  • Patients with an irregular lifestyle or life pattern (e.g., shift workers, patients likely to be jet lagged)
  • Patients with evidence of serious risk of suicide based on the Columbia-Suicide Severity Rating Scale, i.e., active suicidal ideation with some intent to act, with or without a specific plan (a positive response to Suicidal Ideation Items 4 or 5) in the 6 months prior to Screening, OR with evidence of suicidal behavior in the 2 years prior to Screening (a positive response to any of the 5 Suicidal Behavior Items {actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior}), OR who, in the opinion of the investigator, present a serious risk of suicide.

Trial locations and contacts

37 sites in 2 countries.

37 sites in 2 countries

United States32 sites

  • Northwest Clinical Research Center

    Bellevue, Washington, 98007

  • Integrative Clinical Trials LLC

    Brooklyn, New York, 11229

  • Linfritz Research Institute Inc.

    Coral Gables, Florida, 33134

  • Neurology Clinic, P.C.

    Cordova, Tennessee, 38018

  • ATP Clinical Research

    Costa Mesa, California, 92626

  • The Mile High Research Center

    Denver, Colorado, 80218

  • Finlay Medical Research Corp.

    Greenacres City, Florida, 33467

  • Velocity Clinical Research, Inc

    Hallandale, Florida, 33009

  • Rhode Island mood and memory research institute

    Island Park, Rhode Island, 02914

  • Ocean Medical Research

    Jersey City, New Jersey, 08755,

  • K2 Medical Research The Villages

    Lady Lake, Florida, 32159

  • Collaborative Neuroscience Research, LLC

    Long Beach, California, 90806

  • Asclepes Research Centers, P.C. Dba Alliance Research

    Long Beach, California, 90807

  • AMC Research, LLC

    Matthews, North Carolina, 28105

  • Velocity Clinical Research, Inc

    Meridian, Idaho, 83642

  • Verus Clinical research Corp

    Miami, Florida, 33125

  • BioMed Research Institute, Inc.

    Miami, Florida, 33126

  • CCM Clinical Research Group, LLC

    Miami, Florida, 33133

  • Advance Medical Research Center

    Miami, Florida, 33135

  • Allied Biomedical Research Institute (Clinical Trials)

    Miami, Florida, 33135

  • Vitae Research Center LLC.

    Miami, Florida, 33135

  • Stein Gerontological Institute, Inc.

    Miami, Florida, 33137

  • Miami Dade Medical Research Institute

    Miami, Florida, 33176

  • Froedtert & Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • New York University School of Medicine

    New York, New York, 10016

  • K2 Medical Research Winter Garden

    Ocoee, Florida, 34761

  • Interspond, LLC,

    Orlando, Florida, 32807

  • Pacific Research Network, LLC

    San Diego, California, 92103

  • RAA Apex Acquisition LLC DBA Syrentis Clinical Research

    Santa Ana, California, 92705

  • The University of South Florida Board of Trustees,

    Tampa, Florida, 33613

  • Advanced Memory Research Institute of New Jersey

    Toms River, New Jersey, 08755

  • Alzheimer's Research and Treatment Center

    Wellington, Florida, 33414

Other trials in United States

Canada5 sites

  • OCT Research ULC (dba Okanagan Clinical Trials)

    Kelowna, Kelowna, V1Y 1Z9

  • Centricity Research Halifax Multispecialty

    Nova Scotia, Halifax, B3S 1N2

  • Bluewater Clinical Research Group Inc

    Sarnia, Ontario, N7T 4X3

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

    Toronto, Ontario, M4G 3E8

  • Medical Arts Health Research Group

    Vancouver, Vancouver, V7T 1C5

Other trials in Canada

About this study

Official title: Randomized, Delayed Start, Double Blind, Parallel Group, Placebo Controlled, Multicenter Study of Piromelatine 20 mg in Participants With Mild Dementia Due to Alzheimer's Disease

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.

Read the detailed description

This study of piromelatine 20 mg versus placebo in participants with mild dementia due to Alzheimer's disease is conducted as a confirmatory, randomized efficacy and safety study in participants who are 2:107,510,000-107,540,000 polymorphism non-carriers (N=225). Participants will be randomized in a 1:1 allocation ratio to receive either piromelatine 20 mg or placebo for 26 weeks. Medication is to be administered orally, one tablet daily, taken 1-2 hours before going to bed (preferably between 2100h and 2200h) and after food.

To differentiate between symptomatic effects and potential disease modifying effects of piromelatine, there will be a delayed-start open-label extension period of 12 months treatment wherein placebo-treated participants will be treated with piromelatine (20 mg daily) and the piromelatine-treated patients will be continued. This exploratory phase is aimed to continue randomized assignment of piromelatine treatment, long-term (18 months overall) to evaluate its potential disease modifying effect compared to patients in the placebo-randomized group who started the treatment after a 6-month delay.

The primary efficacy analysis (blinded) is planned after completion of the 26 weeks double blind period. If efficacy is not confirmed, then the study will be ended without completing the extension period

Being tested
Piromelatine 20 mg, Placebo
Medical subject headings
Alzheimer Disease

What participants receive

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

  • Piromelatine 20 mgDrug

    Also called Neu-P11

    Tablets

  • PlaceboDrug

    Tablets

Study groups in NCT05267535
Study groupRoleWhat they receive
Piromelatine 20 mgExperimentalPiromelatine 20 mg tablets once daily taken before going to bed, preferably between 2100h and 2300h, and after food consumption.
Receives: Drug: Piromelatine 20 mg
PlaceboPlacebo comparatorMatched placebo tablets, with identical features to the piromelatine tablets, will be used as control treatment
Receives: Drug: Placebo

What is being measured

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

  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 .

    Measured: 26 weeks

Secondary outcomes (3)

  1. Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL)

    The scale typically consists of 23 items. Each item is scored based on the level of independence, with higher scores reflecting better functioning. Total Score Range is 0 to 78. High scores indicate higher functioning and greater independence, while low scores indicate more severe impairment and greater dependence on caregivers.

    Measured: 26 weeks

  2. ADCS-Clinical Global Impression of Change (CGIC)

    The ADCS CGIC is a systematic method for assessing clinically significant change in a clinical trial as viewed by an independent skilled and experienced clinician. The ADCS CGIC focuses on clinicians' observations of change in the patient's cognitive, functional, and behavioral performance since the beginning of a trial.The ADCS CGIC requires the assessor to consider a number of cognitive, functional, and behavioral areas prior to providing an overall "global" assessment of clinical change (Schneider, Olin et al. 1997, Schneider, Clark et al. 2006). The ADCS CGIC assessor must be blinded to all other data for the patient after Visit 2.

    Measured: 26 weeks

  3. Mini-Mental State Examination (MMSE)

    The MMSE is a brief assessment instrument used to assess cognitive function in elderly patients. The MMSE can be used to screen for cognitive impairment and as a measurement of cognition over time and with pharmacologic treatment. The instrument is divided into 2 sections. The first section measures orientation, memory, and attention: the maximum score is 21. The second section tests the ability of the patient to name objects, follow verbal and written commands, write a sentence, and copy figures: the maximum score is 9. The scoring range for the MMSE is 0 30. A positive change indicates an improvement from baseline

    Measured: 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 posted4 Mar 2022
  2. Study start15 Jun 2022
  3. Primary completion12 Sep 2024
  4. Study completion12 Dec 2024

Why it stopped: Treatment with 20 mg piromelatine did not demonstrate efficacy over treatment with placebo based on analysis with the ADAS-Cog 14 subscale and with other cognitive and neuropsychiatric parameters.

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, delayed start, double blind, parallel group, placebo controlled, multicenter study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
216 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05267535
Sponsor's protocol ID
NEUP11-7
Status last verified
May 2026
First submitted
22 Feb 2022
Last updated
9 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hagel JM, Chang L, Li J, Chen X, Yu L, Gallant JA, Facchini PJ. Bioproduction of a Large-Scale Library of Tryptamine Derivatives for Neuropsychiatric Drug Screening. ACS Chem Biol. 2025 Jun 20;20(6):1212-1231. doi: 10.1021/acschembio.4c00857. Epub 2025 May 15.

    PubMed 40375477

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Piromelatine 20 mg in people with Alzheimer's Disease, run by Neurim Pharmaceuticals Ltd. at 37 sites in 2 countries.

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 19 inclusion and 38 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: stopped early, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Canada. 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 9 Sep 2026). 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?

Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog 14) (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 NCT05267535, 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 9 Sep 2026.

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