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Alzheimers DiseasePhase 1NCT07768592

A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2511 in Participants With Early Alzheimer's Disease (AD)

A Phase 1 study testing E2511 and Donepezil in people with Alzheimers Disease, run by Eisai Inc..

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

The primary purpose of this study is to evaluate proof of mechanism (POM) and long-term safety and tolerability of E2511 in participants with Early AD. The study consists of 2 parts. In Part A, participants will be randomly assigned to receive either E2511 or donepezil. In Part B, participants will receive E2511 only. Read more about this study

Who is it for?
Ages 50 to 85 years
Conditions the study is for
Alzheimers Disease
What is being tested?
E2511 and Donepezil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
No sites listed yet
Study dates
15 Oct 2026to 6 May 2030
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

Who may be able to join

  • For participants diagnosed with mild cognitive impairment (MCI) due to AD-intermediate likelihood:
  • Meet the National Institute on Aging and the Alzheimer's Association (NIA-AA) core clinical criteria for MCI due to AD-intermediate likelihood.
  • Have a global Clinical Dementia Rating Scale (CDR) score of 0.5 and a CDR Memory Box score of greater than or equal to (>=) 0.5 at Screening and Baseline.
  • For participants diagnosed with mild AD dementia:
  • Meet the NIA-AA core clinical criteria for probable AD dementia.
  • Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of >=0.5 at Screening and Baseline.
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  • Mini Mental State Examination (MMSE) score >=22 and less than or equal to (<=) 30 at Screening.
  • Evidence of brain amyloid pathology as indicated by one of the following:
  • Plasma phosphorylated tau217 (p-tau217) assay performed at Screening.
  • Historical plasma p-tau217 assay performed before screening.
  • Historical cerebrospinal fluid (CSF) or amyloid PET assessment performed before Screening.
  • Nonsmoking and nonvaping, male or female, aged >=50 years and <=85 years old, at the time of informed consent.
  • Body Mass Index (BMI) greater than 17 and less than 35 at Screening.
  • Have an identified trial partner (defined as a person able to support the participant for the duration of the trial and who spends at least 8 hours per week with the participant). The trial partner must provide separate written informed consent. In addition, this person must be willing and able to provide follow-up information on the participant throughout the course of the trial. This person must, in the opinion of the investigator, spend sufficient time with the participant on a regular basis such that the trial partner can reliably fulfill the trial requirements. A permanent trial partner need not be living in the same residence with the participant. For such a trial partner not residing with the participant, the investigator has to be satisfied that the participant can contact the trial partner readily during the times when the trial partner is not with the participant. If in doubt about whether a participant's care arrangements are suitable for inclusion, the investigator should discuss this with the medical monitor. Trial partners need to participate in person for visits where clinical assessments, such as CDR (global and CDR-SB), take place.
  • Able to undergo CSF lumbar puncture and not receiving any anticoagulant therapy or currently suffering from a medical condition that may require initiation of any anticoagulant therapy at Screening.
  • Provide written informed consent. If a participant lacks the capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required in accordance with local laws, regulations, and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations).
  • Willing and able to comply with all aspects of the protocol including multiple CSF collections.

Who cannot join

  • Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [β-hCG] or human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 International Units per Liter [IU/L] or equivalent units of β-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of trial drug.
  • Females of childbearing potential who:
  • Within 28 days before trial entry, did not use a highly effective method of contraception, which includes any of the following:
  • total abstinence (if it is their preferred and usual lifestyle)
  • an intrauterine device or intrauterine hormone-releasing system (IUS)
  • a contraceptive implant
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  • an oral contraceptive (participant must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing and must agree to stay on the same dose of the oral contraceptive throughout the trial and for 28 days after trial drug discontinuation)
  • have a vasectomized partner with confirmed azoospermia.
  • Do not agree to use a highly effective method of contraception (as described above) throughout the entire trial period and for 28 days after trial drug discontinuation.
  • NOTE: It is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, i.e., double-barrier methods of contraception such as latex or synthetic condom plus diaphragm or cervical/vault cap with spermicide. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
  • Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (i.e., the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the trial period and for 5 times the half-life of the trial drug plus 90 days after trial drug discontinuation). No sperm donation is allowed during the trial period and for 5 times the half-life of the trial drug plus 90 days after trial drug discontinuation.
  • Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's MCI or AD.
  • History of transient ischemic attacks, stroke, or seizures within 12 months of Screening.
  • Any lifetime history of psychiatric disease (including but not limited to depression or other mood disorders, bipolar disorder, psychotic disorders, including schizophrenia, panic attacks, anxiety disorders).
  • Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening (i.e., answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS).
  • Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS).
  • Contraindications to magnetic resonance imaging (MRI) scanning, including cardiac pacemaker/defibrillator, and ferromagnetic metal implants (eg, in skull and cardiac devices other than those approved as safe for use in MRI scanners).
  • Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than AD.
  • Other significant pathological findings on brain MRI at Screening, including but not limited to: evidence of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors (however, lesions diagnosed as meningiomas or arachnoid cysts and less than 1 centimeter [cm] at their greatest diameter need not be exclusionary). Other minor or clinically insignificant MRI abnormalities, as agreed by the medical monitor and after discussion with the investigator, may not be exclusionary.
  • Malignant neoplasms within 3 years of Screening (except for basal or squamous cell carcinoma in situ of the skin, localized prostate cancer in male participants, or localized breast cancer in female participants). Participants who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before Screening need not be excluded.
  • A clinically significant ECG abnormality, including a marked prolonged corrected QT interval (Fridericia's Correction Formula) (eg, a repeated demonstration of a QTcF interval greater than [>] 450 milliseconds [ms]).
  • Participants with a bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5). Participants who are on anticoagulant therapy are not permitted to be enrolled.
  • Have thyroid-stimulating hormone above the normal range. Other tests of thyroid function with results outside the normal range should only be exclusionary if they are considered clinically significant by the investigator. This applies to all participants whether or not they are taking thyroid supplements. If the thyroid-stimulating hormone returns to normal range with thyroid replacement therapy, then participants may be allowed to enroll without rescreening if they meet all other inclusion criteria and did not meet any exclusion criteria.
  • Abnormally low serum vitamin B12 levels for the testing laboratory (if a participant is taking vitamin B12 injections, level should be at or above the lower limit of normal for the testing laboratory). Levels of vitamin B12 may be confirmed with reflex testing to include methylmalonic acid analysis, if available in the region. If vitamin B12 levels return to normal range with supplement treatment, then participants may be allowed to enroll without rescreening if they meet all other inclusion criteria and did not meet any exclusion criteria.
  • Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, and renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the trial assessments. Any other medical conditions (eg, cardiac, respiratory, gastrointestinal, and renal disease) that are not stably and adequately controlled or that in the opinion of the investigator(s) could affect the participant's safety or interfere with the trial assessments.
  • Any history of or concomitant medical condition that in the opinion of the investigator(s) would compromise the participant's ability to safely complete the trial.
  • Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the trial. Planned surgery that requires only local anesthesia and that can be undertaken as a day case without inpatient stay postoperatively need not result in exclusion if in the opinion of the investigator this operation does not interfere with trial procedures and participant's safety.
  • Known to be human immunodeficiency virus positive.
  • Known or suspected history of drug or alcohol abuse or dependence within 2 years before Screening or a positive urine drug test at Screening. Participants who test positive for benzodiazepines or opioids in urine drug testing need not be excluded if, in the clinical opinion of the investigator, this is due to the participant taking prior/concomitant medications containing benzodiazepines or opioids for a medical condition and not due to drug abuse.
  • Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately.
  • Active viral hepatitis (A, B, or C) as demonstrated by positive serology at Screening.
  • Currently enrolled in another clinical trial or used any investigational drug or device within 28 days or 5 half-lives of the other investigational drug, whichever is longer, preceding informed consent.
  • Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing.
  • Participants who contravene the restrictions on medications, food, beverages, physical activities, and others as defined in the protocol at Screening or Baseline.
  • Participants with contraindications to lumbar puncture.
  • Known hypersensitivity to donepezil hydrochloride or to piperidine derivatives.
  • Taking a cholinesterase inhibitor unless willing to discontinue cholinesterase inhibitor treatment for 21 days before Screening and until the last visit during the Core Trial.
  • Participation in a clinical trial for AD involving any antisense oligonucleotide or silencing ribonucleic acid (RNA) therapies targeting amyloid or tau unless it can be documented that the participant only received placebo.
  • Participation in a clinical trial for AD involving pharmaceutical intervention other than antisense oligonucleotide or silencing RNA therapies (eg, small molecules, monoclonal antibodies) within 6 months of Screening unless it can be documented that the participant only received placebo.
  • Participants who have taken approved anti-amyloid monoclonal antibodies (eg, LEQEMBI, KISUNLA) within 6 months of Screening.
  • Any history of surgery that may affect pharmacokinetic (PK) profiles of trial drug (eg, hepatectomy, nephrectomy, digestive organ resection) or participants who have a congenital abnormality in metabolism at Screening.
  • Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Eisai Medical Information contact

+1-888-274-2378

esi_medinfo@eisai.com

About this study

Official title: A Proof-of-Mechanism, Open-Label, Parallel Group Study With an Open-Label Extension Phase to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2511 in Participants With Early Alzheimer's Disease

The primary purpose of this study is to evaluate proof of mechanism (POM) and long-term safety and tolerability of E2511 in participants with Early AD. The study consists of 2 parts. In Part A, participants will be randomly assigned to receive either E2511 or donepezil. In Part B, participants will receive E2511 only. Once Part A and Part B participants complete the Core Trial (which includes Pretreatment and Treatment phases) they will have the option to enter the Extension Phase where they will receive E2511 for 18 months.

Being tested
E2511, Donepezil
Medical subject headings
Alzheimer Disease

What participants receive

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

  • E2511Drug

    E2511 oral tablets.

  • DonepezilDrug

    Also called Aricept

    Donepezil oral tablets.

Study groups in NCT07768592
Study groupRoleWhat they receive
Part A: E2511 Dose AExperimentalNot described
Receives: Drug: E2511
Part A: Donepezil Dose AExperimentalNot described
Receives: Drug: Donepezil
Part B: E2511 Dose BExperimentalNot described
Receives: Drug: E2511

What is being measured

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

  1. Part A (Core Trial): Change from Baseline in [11C]MK-6884 Positron Emission Tomography (PET) Using Non-Displaceable Binding Potential (BPND) at 14 Days

    Measured: Baseline up to Day 14

  2. Part A and B (Extension Phase): Number of Participants With Adverse Events (AEs)

    Measured: Up to 91 weeks

  3. Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Vital Sign Values

    Measured: From Week 13 up to Week 91

  4. Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values

    Measured: From Week 13 up to Week 91

  5. Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Physical Exam

    Measured: From Week 13 up to Week 91

  6. Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Neurological Exam

    Measured: From Week 13 up to Week 91

  7. Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Laboratory Safety Tests Values

    Measured: From Week 13 up to Week 91

  8. Part A and B (Extension Phase): Number of Participants With Suicidality as Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)

    The C-SSRS is an interview-based rating scale to systematically assess any suicidality, suicidal behavior, or suicidal ideation. Any suicidality is emergence of any suicidal ideation or suicidal behavior. Any suicidal behavior is indicated when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation is indicated when response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.

    Measured: Up to 91 weeks

Secondary outcomes (15)

  1. Part A and B (Core Trial): Number of Participants With AEs

    Measured: Part A: Up to 21 weeks; Part B: Up to 17 weeks

  2. Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Vital Sign Values

    Measured: Part A: Up to 21 weeks; Part B: Up to 17 weeks

  3. Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in ECG Values

    Measured: Part A: Up to 21 weeks; Part B: Up to 17 weeks

  4. Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Laboratory Safety Tests Values

    Measured: Part A: Up to 21 weeks; Part B: Up to 17 weeks

  5. Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Physical Exam

    Measured: Part A: Up to 21 weeks; Part B: Up to 17 weeks

  6. Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Neurological Exam

    Measured: Part A: Up to 21 weeks; Part B: Up to 17 weeks

  7. Part A and B (Core Trial): Number of Participants With Suicidality as Assessed by C-SSRS

    The C-SSRS is an interview-based rating scale to systematically assess any suicidality, suicidal behavior, or suicidal ideation. Any suicidality is emergence of any suicidal ideation or suicidal behavior. Any suicidal behavior is indicated when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation is indicated when response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.

    Measured: Part A: Up to 21 weeks; Part B: Up to 17 weeks

  8. Part A and B (Core Trial): Cmax: Maximum Observed Plasma Concentration of E2511

    Measured: Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14

  9. Part A and B (Core Trial): Tmax: Time to reach Cmax of E2511

    Measured: Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14

  10. Part A and B (Core Trial): AUC(0-24h): Area Under the Plasma Concentration-Time Curve From Zero Time to 24 Hours of E2511

    Measured: Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14

  11. Part A and B (Core Trial): AUC(0-t): Area Under the Plasma Concentration-Time Curve From Zero Time to Time of Last Quantifiable Concentration of E2511

    Measured: Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14

  12. Part A and B (Core Trial): AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Zero Time Extrapolated to Infinite Time of E2511

    Measured: Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14

  13. Part A and B (Core Trial): t1/2: Terminal Elimination Half-Life of E2511

    Measured: Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14

  14. Part A and B (Core Trial): CL/F: Apparent Total Clearance of E2511 Following Oral Administration on Day 1

    Measured: Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14

  15. Part A and B (Extension Phase): Change from Baseline in Standard Uptake Value Ratio (SUVR) of [18F]fluoroethoxybenzovesamicol (FEOBV) at 12 and 18 Months

    Measured: Baseline, 12 and 18 Months

Timeline

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

  1. First posted17 Aug 2026
  2. Study start15 Oct 2026 (estimated)
  3. Primary completion6 May 2030 (estimated)
  4. Study completion6 May 2030 (estimated)

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07768592
Sponsor's protocol ID
E2511-A001-102
Status last verified
Jun 2026
First submitted
12 Aug 2026
Last updated
17 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing E2511 and Donepezil in people with Alzheimers Disease, run by Eisai Inc..

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 17 inclusion and 42 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: opening soon, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Eisai Medical Information (+1-888-274-2378, esi_medinfo@eisai.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A (Core Trial): Change from Baseline in [11C]MK-6884 Positron Emission Tomography (PET) Using Non-Displaceable Binding Potential (BPND) at 14 Days (time frame: Baseline up to Day 14). The study lists 8 primary outcomes in all. 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 NCT07768592.

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 17 Aug 2026.

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