| Eligibility |
Inclusion Criteria:
1. Age 55-80 years (both inclusive), male or female.
2. Body mass index between 18.5 to 33.0 kg/m2 (both inclusive).
3. Should meet the criteria for early clinical stage Alzheimer's Disease (AD) according
to the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria
research framework:
1. Gradual and progressive change in memory function reported by patient or
informant over more than 6 months,
2. Clinical syndrome of Mild Cognitive Impairment (MCI) due to AD or mild AD
dementia,
3. An Mini-Mental State Exam (MMSE) score = 20 at screening,
4. Biomarker classification according to the Amyloid/Tau/Neurodegeneration (ATN) as
A+T+N+ or A+T+N- based upon:
(i) Cerebrospinal fluid (CSF) profile consistent with AD (an Aß42 concentration of
<1000 pg/mL AND phosphorylated tau (p-tau) >19 pg/mL, or a ratio of p-tau/Aß42 of
=0.020) taken during the screening period prior to the day of the first dose of study
medication, or
(ii) Documented evidence of a CSF profile consistent with AD obtained with the
previous 12 months, or
(iii) Documented amyloid positron emission tomography (PET) scan evidence acquired
within the previous 12 months.
4. A reliable and competent trial partner/caregiver who can assist and witness dosing and
is willing to accompany the patient to all visits. The trial partner/caregiver should
understand the nature of the trial and adhere to trial requirements (e.g., visit
schedules, evaluations) and confirm this by co-signing the informed consent of the
patient or signing of a separate informed consent of the partner/caregiver according
to the local requirements.
5. If a patient is taking medication, supplements or vitamins that may have an influence
on oxidative stress, cognition and/or EEG, the dose must be stable at screening for at
least one month, and the patient must be willing to remain on the same treatment and
dose for the duration of the trial.
6. A male patient abstains from sexual intercourse, or is vasectomized (> 6 months), or
will use a condom with spermicide during sexual intercourse during the trial and for
three months after participation in the trial and will abstain from sperm donation
during the trial and for three months after participation in the trial.
7. A female patient should not be of reproductive potential:
A female patient who is not of reproductive potential is defined as one who:
1. Has reached natural menopause (defined as 6 months of spontaneous amenorrhea with
serum follicle-stimulating hormone [FSH] levels in the postmenopausal range as
determined by the local laboratory, or 12 months of spontaneous amenorrhea);
2. Is 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy; or
3. Has undergone bilateral tubal ligation. Spontaneous amenorrhea does not include
cases for which there is an underlying disease that causes amenorrhea (e.g.,
anorexia nervosa).
8. Capable of providing informed consent and complying with trial procedures.
Exclusion Criteria:
1. A known history of stroke that is clinically important in the investigator's opinion.
2. Evidence of a clinically relevant neurological disorder other than AD at screening,
including but not limited to: vascular dementia, Parkinson's disease, frontotemporal
dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis,
progressive supranuclear palsy, dementia with Lewy bodies, other types of dementia,
neurosyphilis or head trauma with loss of consciousness that led to persistent
cognitive deficits.
3. A history of seizures or epilepsy within the last 5 years before screening.
4. Evidence of a clinically relevant or unstable psychiatric disorder, based on the 5th
edition after text revision of the Diagnostic and Statistical Manual of Mental
Disorders (DSM-5TM) criteria, including schizophrenia or other psychotic disorder,
bipolar disorder, major depression, or delirium. Major depression in remission is not
exclusionary.
5. Renal impairment as indicated by a creatinine clearance of less than 50 mL/min as
calculated by the Cockcroft Gault equation.
6. Patient has a history of any of the following conditions:
1. Clinically significant hepatic disease,
2. AST or ALT levels of = 2 times upper limit of normal (ULN),
3. Biliary tract disease,
4. Patient has a positive screening test for HIV, hepatitis B or C.
7. Presence of any of the following clinical conditions:
1. Unstable cardiac, pulmonary, endocrine, hematologic or active infectious disease,
2. Unstable psychiatric illness defined as psychosis, untreated major depression
within 90 days of the screening visit,
3. A history of cancer within the past 3 years prior to screening other than treated
squamous cell carcinoma, basal cell carcinoma and melanoma in situ, or in-situ
prostate cancer or in-situ breast cancer which have been fully removed and are
considered cured
8. History or signs/symptoms of lumbar spine/disc disease including but not limited to
scoliosis, herniation, or any other contraindication to lumbar puncture.
9. History of known sensitivity or intolerability to edaravone, related substances of
edaravone, or to any of the excipients.
10. Current substance or alcohol dependence.
11. Exposure to any investigational drug within 30 days of the screening visit.
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