Clinical trial: Efficacy and Safety of 26-Week Treatment of AR1001 in Patients With Mild to Moderate Alzheimer's Disease (NCT03625622)

Eligibility criteria:
Inclusion Criteria

          1. Male or female subjects aged 55-80 years at the time of signing the Informed Consent
             Form.

          2. Subjects (or subject's legally acceptable representative) and caregiver(s) who can
             sign an Informed Consent to participate in the study. Same caregiver(s) must assist
             the subject throughout the entire duration of the study.

          3. Subjects who have a diagnosis of probable Alzheimer's disease according to the NIA-AA
             (National Institute of Aging and Alzheimer's Associations, 2011) criteria with mild to
             moderate dementia (stage 4 - 5) at screening.

          4. Subjects who have mild-to-moderate cognitive impairment with MMSE Score of 16-26 at
             screening.

          5. Subjects who have an MRI (either 1.5T or 3T) or CT scan performed after onset of
             symptoms and prior to randomization with findings consistent with the diagnosis of
             dementia due to Alzheimer's disease and without any other clinically significant
             comorbid pathologies.

          6. Subjects who have one (or more) identified adult study partner(s) who, in the opinion
             of the investigator, has sufficient contact with and knowledge about the subject as to
             be able to report knowledgeably about the subject's safety, compliance and adherence,
             cognition, function, and behavior.

        Exclusion Criteria

          1. Subjects who are female who are pregnant, nursing, or of childbearing potential and
             not practicing effective contraception.

          2. Subjects who have signs of delirium.

          3. Subjects who have had a cortical stroke within the preceding 2 years.

          4. Subjects who have any diagnosis of dementia other than that related to Alzheimer's
             Disease, including concomitant vascular dementia.

          5. Subjects who have a PET scan performed after onset of symptoms with negative amyloid
             results.

          6. Subjects with a history of myocardial infarction, unstable angina, New York Heart
             Association (NYHA) class III or IV heart failure or stroke within the last 12 months.

          7. Subjects with uncontrolled hypertension (systolic blood pressure >160mm Hg or
             diastolic blood pressure > 95mm Hg) or hypotension (systolic blood pressure <90mm Hg
             or diastolic blood pressure <50mm Hg).

          8. Subjects who have clinically significant renal impairment (creatinine > 1.5x ULN) or
             hepatic impairment (AST or ALT > 2.5x ULN or total bilirubin > 1.5x ULN).

          9. Subjects who have history of cancer or malignant tumor within 5 years prior to
             screening with the exception of:

               1. Basal or squamous cell carcinoma of the skin or cervical dysplasia which has been
                  adequately treated.

               2. In situ Grade 1 cervical cancer, fully treated at least 2 years prior to
                  screening and without recurrence.

               3. Prostate cancer, confined to the prostate gland, which has been adequately
                  treated (surgery and/or radiation) with normal or low and stable PSA levels for 2
                  years prior to screening.

         10. Subjects who have history of untreated thyroid disorder or a seizure disorder.

         11. Subjects who are being treated, or likely to require treatment during the study, with
             any medications prohibited by the study protocol.

         12. Subjects who have participated in any investigational drug or device trial within the
             previous 30 days or five half-lives of the investigational drug at screening,
             whichever one is longer.

         13. Subjects who have any other clinically significant abnormal result in laboratory tests
             such as abnormally low B12 or high TSH levels, as determined by the Investigator.

         14. Subjects with any current psychiatric diagnosis other than AD if, in the judgment of
             the investigator, the psychiatric disorder or symptom is likely to confound
             interpretation of drug effect, affect cognitive assessments, or affect the subject's
             ability to complete the study.

         15. Subjects whose treatment with FDA-approved AD medication (donepezil, galantamine,
             memantine, rivastigmine or their combinations) has not been stable for at least 3
             months prior to screening. Treatment and dosing should remain stable, with no changes
             throughout the trial.

         16. Subjects who are currently receiving (or unable to stop use for at least 21 days [3
             weeks] prior to receiving the first dose of the AR1001 and throughout the study)
             prescription or non-prescription medications or other products known to be moderate or
             potent inhibitors/inducers of CYP3A4.

         17. Subjects who have had any intake of grapefruit, grapefruit juice, Seville oranges,
             Seville orange marmalade, or other products containing grapefruit or Seville oranges
             within 7 days of the first administration of the AR1001 and throughout the study.

         18. Subjects, in the opinion of the Investigator, who are unsuitable to participate in the
             study.

        Extension Phase Continuation Criterion

        1. Subjects enrolled in AR1001-ADP2-US01 and completed 26 weeks of assigned dosing.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 55 Years old.
Subject must be at most 80 Years

Patient description (medical language): A 70-year-old man comes to the office accompanied by his wife.  The patient has experienced progressive memory loss over the last years.  He needs help with some of his routine activities, such as paying bills.  The patient's wife says, "He used to be such an independent person, but now he needs help with many things, even finding direction to home!"  Medical history includes hypertension, hyperlipidemia, and type 2 diabetes mellitus.  Family history includes Alzheimer disease in his father.  MRI reveals diffuse cortical and hippocampal atrophy. The diagnosis of AD is made using the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria.

Patient description (patient's own words): I am a 70-year-old man, and I paid a visit to the doctor with my wife the other day. I noticed that I tend to forget small things and that my memory has decreased over the past few years. I even ask my wife to help me out with my daily routine. I used to be the one paying the bills, but now she has to give me a hand. My wife mentioned to the doctor that I used to be independent and that I tend to forget where we live. I suffer from hypertension, high cholesterol, and type 2 diabetes. My poor dad was suffering from Alzheimer disease, so I hope I'm not going to end the same way! I did an MRI and they found out that some part of my brain was decreasing. I also did an Alzheimer test.

Does the patient match the trial criteria? Entailment