| Eligibility |
Inclusion Criteria:
1. Subjects between the ages of 50 and 85 (inclusive) at the time of Screening Visit 1.
Subjects 86 to 90 years of age (inclusive) can be enrolled, provided that the Medical
Monitor reviews the subject's medical condition during the screening process and
approves enrolment.
2. Dementia of mild to moderate severity, as classified by MMSE score between 14 to 26,
inclusive, at Screening Visit 1.
3. Meets diagnostic clinical criteria of probable Alzheimer's dementia according to the
National Institute on Aging and the Alzheimer's Association (NIA-AA) [25].
4. Magnetic resonance imaging prior to Visit 3 (Baseline) compatible with a diagnosis of
probable AD.
5. Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) brain scan showing a pattern
typical for AD according to central PET reader (with areas of glucose hypometabolism
in posterior cingulate, temporal, parietal, and/or prefrontal cortices, as per
criteria in imaging manual).
6. Confirmed APOE negative genotype result obtained by the central laboratory prior to
Screening Visit 2 or documented prior to screening.
7. Subjects taking the following cholinesterase inhibitors (ChEI): donepezil,
galantamine, or rivastigmine; and/or GV-971, and/or memantine and/or other agents
which may impact cognition (e.g., Souvenaid®, NeuroAidTM, Cerefolin®, Gingko biloba,
etc) are eligible for enrolment:
1. If the subject has been taking such medication(s)/products for 3 months or more
at Screening Visit 1.
2. If the current dosage regimen is within the approved dose range.
3. The daily dose has remained unchanged for at least 6 weeks prior to screening.
4. If the dose is not expected to change during trial participation.
5. Tacrine use is not allowed.
8. In the opinion of the Investigator, the subject's medical condition, except for
dementia, has been stable for at least 3 consecutive months prior to Screening Visit
1.
9. Subjects do not have active suicidal thoughts (answers 'yes' to questions 4 or 5, on
the Columbia-Suicide Severity Rating Scale [C-SSRS]) within 6 months preceding
Screening Visit 2 or Visit 3 (Baseline). Additionally, subjects have no active history
of suicide attempt in the previous 2 years or more than 1 lifetime suicide attempt,
nor are they at serious suicidal risk, in the opinion of the Investigator.
10. The subject is able to comply with protocol testing and procedures for the entire
length of the trial.
11. Has a permanent caregiver (subject's caregiver is not expected to change during the
trial) who is willing to attend all visits, oversee the subject's compliance with
protocol-specified procedures and IP administration, and report on subject's status.
Caregiver must have, in the opinion of the Investigator, enough contact with the
subject to be able to perform the duties described above.
12. The subject and caregiver are, in the Investigator's judgement, proficient in the
language in which the trial assessments will be completed, and have hearing, vision
and physical abilities adequate to perform assessments (corrective aids allowed).
13. Subject and caregiver must provide full written informed consent prior to the
performance of any protocol-specified procedure; or if subject is unable to provide
informed consent due to cognitive status, provision of informed consent by cognitively
intact legally acceptable representative (where this is in accordance with local laws,
regulations and ethics committee policy).
14. Subject is able to ingest oral medication.
15. Subject is able to tolerate a 5 g dose of tricaprilin (formulated as 12.5 g of
AC-SD-03) as per sentinel dose challenge at Visit 3 (Baseline).
Exclusion Criteria:
1. Current use or use within 3 months of Visit 3 (Baseline), of Axona® or other
MCT-containing products. Use of coconut oil up to 15 mL (1 tablespoon) per day is
allowed. Use of MCT-containing products is not allowed at any time during trial
participation.
2. Use of any other investigational agent within 60 days prior to Screening Visit 1.
3. Has a known allergy or hypersensitivity to triglycerides.
4. In the opinion of the Investigator, has presence or history of an advanced, severe,
progressive, or unstable disease of any type that could interfere with efficacy and
safety assessments, or put the subject at risk.
5. Has any medical or neurological condition, other than AD, that could explain the
subject's dementia (e.g., structural abnormality, traumatic brain injury, stroke,
epilepsy, Parkinson's disease, alcohol-related dementia, etc.)
6. Has a modified Hachinski Ischemia score greater than (>) 4 at Screening Visit 2.
7. Has a history or clinical laboratory evidence of cerebrovascular disease (stroke,
transient ischemic attack, haemorrhage), or diagnosis of possible, probable, or
definite vascular dementia at Screening Visit 1 in accordance with National Institute
of Neurological Disorders and Stroke criteria.
8. Brain MRI performed at Screening (prior to Visit 3) (per centrally read MRI) that
shows evidence of any of the following:
1. Acute, sub-acute or chronic haemorrhage.
2. Cortical infarct (defined as > 1.5 cm in diameter).
3. > 1 lacunar infarct (defined as < 1.5 cm in diameter).
4. Superficial siderosis.
5. History of diffuse white matter disease as defined by a score of 3 on the
age-related white matter changes scale [26].
6. Any finding that, in the opinion of the Investigator, might be a contributing
cause of subject's dementia, might pose a risk to the subject, or might prevent a
satisfactory MRI assessment for safety monitoring.
9. Has a history or clinical laboratory evidence of moderate congestive heart failure
defined by the New York Heart Association Criteria (Class I to IV).
10. Clinically significant ECG abnormalities at Screening Visit 2, for example:
1. Evidence of atrial fibrillation on ECG or history of atrial fibrillation that is
not currently controlled
2. QTcF at > 450 ms in males or > 470 ms in females, or low or flat T waves making
measurement of QT interval unreliable
11. Has a history of new ischemic or congestive cardiovascular event within the 3 months
prior to Visit 3 (Baseline).
12. Has a history of or current major psychiatric illness such as schizophrenia or bipolar
affective disorder.
13. Has a clinician-administered Patient Health Questionnaire (PHQ)-9 score of = 10 or in
the Investigator's opinion, depression of a severity that would impact cognitive
assessments.
14. Subjects with insulin dependent diabetes.
15. Subjects with uncontrolled hypertension defined as:
1. average of 3 systolic blood pressure [SBP]/diastolic blood pressure [DBP]
readings > 165/100 mmHg at Screening Visit 2 (blood pressure measurements
exceeding these limits may be repeated as warranted by the Investigator, but
values must be within the specified limits for the subject to be eligible for the
study),
2. or persistent SBP/DBP readings > 180/100 mmHg 3 months prior to Baseline (Visit
3, Day 1) that in the opinion of the Investigator are indicative of chronic
uncontrolled hypertension.
16. Subjects with orthostatic hypotension, defined as a drop of >20 mmHg systolic blood
pressure upon standing upright from a seated position within 3 minutes, at Screening
Visit 2; testing for orthostatic hypotension may be repeated at Investigator's
discretion if there is reason to believe the condition is temporary after addressing
the temporary cause.
17. At Screening Visit 2, clinically significant:
1. anaemia (haemoglobin < 11 g/dL for males or < 10 g/dL for females)
2. renal disease or insufficiency, including but not limited to a creatinine value
of > 1.9 mg/dL (> 170 µmol/L)
3. hypothyroidism
18. At Screening Visit 2, laboratory test values (potential to repeat at Investigators
discretion):
1. ALT, AST, total bilirubin, or alkaline phosphatase > 2.5 times the ULN laboratory
range, or history of severe hepatobiliary disease (e.g., hepatitis B or C, or
cirrhosis [Childs-Pugh Classes B/C] without enzyme elevation)
2. Fasting triglycerides > 2.5 times the ULN
3. Cholesterol > 240 mg/dL
19. Clinically significant Vitamin B12 deficiency within 12 months prior to Visit 1;
however, subjects on stable replacement therapy for a minimum of 1 month immediately
prior to Visit 1 may be included.
20. The following GI conditions are exclusionary as described below:
1. Inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease), GI
bleed (upper or lower), or peptic ulcer disease; any of these conditions are
exclusionary, if active in the past 5 years. Subjects with remote quiescent
disease, at Investigators discretion (and CER Committee) are not excluded.
2. Subjects with current or a history of (within the last 5 years) any of the
following conditions are excluded: complicated reflux disease (e.g., Barrett's
oesophagus, stricture, ulcer, haemorrhage), or severe GERD that, in the opinion
of the Investigator, is not well-controlled by medication.
3. Irritable bowel syndrome, diverticular disease (e.g., diverticulosis, or
diverticulitis), or chronic gastritis; any of these conditions are exclusionary
if there has been an acute event within 1 year prior to Screening Visit 1.
21. Has donated = 2 units of blood within the 1 month prior to Screening Visit 1.
22. Has a history of alcohol or drug abuse within the 6 months prior to Visit 1 or has
tested positive upon urine drug screen at Screening Visit 2.
23. Subject or caregiver is an immediate family member or employee of the clinical site,
Sponsor, or of the Sponsor's agents.
24. Has any current or history of neoplasm or malignancy, other than excised or treated
basal cell carcinoma. The following exceptions may be made after discussion with the
Medical Monitor:
1. Subjects with cancers in remission more than 5 years prior to Screening.
2. Subjects with a history of excised or treated squamous carcinoma of the skin.
3. Subjects with prostate cancer in situ.
25. Subject has a scheduled (or is expected to have scheduled) hospitalisation and/or
surgery during the trial
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