Alzheimers Disease
Conditions
Brief 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. 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.
Interventions
DRUGE2511
E2511 oral tablets.
DRUGDonepezil
Donepezil oral tablets.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. For participants diagnosed with mild cognitive impairment (MCI) due to AD-intermediate likelihood: 1. Meet the National Institute on Aging and the Alzheimer's Association (NIA-AA) core clinical criteria for MCI due to AD-intermediate likelihood. 2. 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. 2. For participants diagnosed with mild AD dementia: 1. Meet the NIA-AA core clinical criteria for probable AD dementia. 2. Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of \>=0.5 at Screening and Baseline. 3. Mini Mental State Examination (MMSE) score \>=22 and less than or equal to (\<=) 30 at Screening. 4. Evidence of brain amyloid pathology as indicated by one of the following: 1. Plasma phosphorylated tau217 (p-tau217) assay performed at Screening. 2. Historical plasma p-tau217 assay performed before screening. 3. Historical cerebrospinal fluid (CSF) or amyloid PET assessment performed before Screening. 5. Nonsmoking and nonvaping, male or female, aged \>=50 years and \<=85 years old, at the time of informed consent. 6. Body Mass Index (BMI) greater than 17 and less than 35 at Screening. 7. 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. 8. 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. 9. 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). 10. Willing and able to comply with all aspects of the protocol including multiple CSF collections.
Exclusion criteria
1. 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. 2. 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 * 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). 3. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A and B (Extension Phase): Number of Participants With Suicidality as Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | Up to 91 weeks | 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. |
| Part A (Core Trial): Change from Baseline in [11C]MK-6884 Positron Emission Tomography (PET) Using Non-Displaceable Binding Potential (BPND) at 14 Days | Baseline up to Day 14 | — |
| Part A and B (Extension Phase): Number of Participants With Adverse Events (AEs) | Up to 91 weeks | — |
| Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Vital Sign Values | From Week 13 up to Week 91 | — |
| Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values | From Week 13 up to Week 91 | — |
| Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Physical Exam | From Week 13 up to Week 91 | — |
| Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Neurological Exam | From Week 13 up to Week 91 | — |
| Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Laboratory Safety Tests Values | From Week 13 up to Week 91 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A and B (Core Trial): Number of Participants With AEs | Part A: Up to 21 weeks; Part B: Up to 17 weeks | — |
| Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Vital Sign Values | Part A: Up to 21 weeks; Part B: Up to 17 weeks | — |
| Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in ECG Values | Part A: Up to 21 weeks; Part B: Up to 17 weeks | — |
| Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Laboratory Safety Tests Values | Part A: Up to 21 weeks; Part B: Up to 17 weeks | — |
| Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Physical Exam | Part A: Up to 21 weeks; Part B: Up to 17 weeks | — |
| Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Neurological Exam | Part A: Up to 21 weeks; Part B: Up to 17 weeks | — |
| 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 | Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14 | — |
| Part A and B (Core Trial): Number of Participants With Suicidality as Assessed by C-SSRS | Part A: Up to 21 weeks; Part B: Up to 17 weeks | 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. |
| Part A and B (Core Trial): t1/2: Terminal Elimination Half-Life of E2511 | Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14 | — |
| Part A and B (Core Trial): CL/F: Apparent Total Clearance of E2511 Following Oral Administration on Day 1 | Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14 | — |
| Part A and B (Extension Phase): Change from Baseline in Standard Uptake Value Ratio (SUVR) of [18F]fluoroethoxybenzovesamicol (FEOBV) at 12 and 18 Months | Baseline, 12 and 18 Months | — |
| 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 | Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14 | — |
| Part A and B (Core Trial): Cmax: Maximum Observed Plasma Concentration of E2511 | Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14 | — |
| Part A and B (Core Trial): Tmax: Time to reach Cmax of E2511 | Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14 | — |
| Part A and B (Core Trial): AUC(0-24h): Area Under the Plasma Concentration-Time Curve From Zero Time to 24 Hours of E2511 | Part A: From Day 1 up to Day 42; Part B: From Day 1 up to Day 14 | — |
Contacts
CONTACTEisai Medical Information
Outcome results
None listed