| Eligibility |
Inclusion Criteria:
- Participant must be 45 80 years of age inclusive, at the time of signing the informed
consent
- Cohorts A-C participants who are overtly healthy as determined by medical evaluation
including medical history, physical examination, laboratory tests, and cardiac
monitoring.
- Cohort D - AD as characterized by the following clinical, cognitive, and functional
criteria.
- Diagnosis of a clinical syndrome of cognitive impairment consistent with
prodromal AD per International Working Group (IWG) diagnostic criteria or mild AD
per National Institute on Aging - Alzheimer's Association (NIAA-AA) diagnostic
criteria
- Self or informant report of memory decline
- Mini-Mental State Examination (MMSE) scores between 18-27 inclusive within the
last 4 months
- Objective memory loss by education-adjusted Wechsler Memory Scale Logical Memory
II consistent with mild cognitive impairment with Alzheimer's disease (MCI AD) or
mild AD
- Absence of significant levels of impairment in other cognitive assessments
- Cohort D - Previous brain imaging study, such as magnetic resonance imaging (MRI)
and/or computed tomography (CT), consistent with a diagnosis of probably AD without
any other clinically significant co-morbid pathologies within 12 months prior to the
Screening Visit. If there has been a significant change in clinical status suggestive
of stroke or other possible central neurological disease with onset between the time
of the last MRI or CT and the Screening evaluation, the scan should be repeated during
Screening procedures if considered appropriate by the Investigator OR Screening
cerebrospinal fluid (CSF) results consistent with the presence of amyloid pathology.
- Cohort D - No active depression and a Geriatric Depression Score of <6.
- Cohort D - Absence of other (non-AD) types of dementia.
- Cohort D - Participants previously enrolled in an AD clinical trial involving a
disease modifying or symptomatic therapeutic agent may enroll in this study if
treatment with the symptomatic therapeutic agent ended more than 6 months before the
first dose of NTRX 07-SDD in this study.
- Body weight within 55 110 kg and body mass index (BMI) within the range 18 35 kg/m2
(inclusive)
- Male or Female
- The effects of NTRX 07 on pregnancy, fetal development, and excretion in breast milk
is currently unknown. Contraceptive use should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.
- Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the subject information sheet, informed
consent form (ICF) and in this protocol.
Exclusion Criteria:
- Reported history or presence of clinically significant history of or current
cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological,
hematological, or neurological disorders capable of significantly altering the
absorption, metabolism, or elimination of drugs; constituting a risk when taking the
study intervention; or interfering with the interpretation of data. Participants with
stable well controlled conditions may be accepted on review with the Investigator and
sponsor.
- Reported current or chronic history of clinically significant liver disease. This
includes but is not limited to hepatitis virus infections, drug- or alcohol-related
liver disease, nonalcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis,
Wilson's disease, a-1 antitrypsin deficiency, primary biliary cholangitis, primary
sclerosing cholangitis, or any other liver disease considered clinically significant
by the investigator.
- Reported hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or
asymptomatic gallstones).
- Cohort D - Reside in a nursing home or assisted care facility with need for direct
continuous medical care and nursing supervision. Participant may reside in such
facilities provided continuous direct medical care is not required.
- Cohort D - Unable to provide for self for basic activities of daily living.
- Cohort D - Major structural brain disease by reported history or chart review (eg,
ischemic infarcts, subdural hematoma, hemorrhage, hydrocephalus, brain tumors,
multiple subcortical ischemic lesions, or a single lesion in a critical region eg,
thalamus, hippocampus).
- Any other reported history of central nervous system (CNS) trauma (eg, contusion), or
infections that affect brain function (eg, human immunodeficiency virus [HIV],
syphilis), history of seizures
- Diagnosis of schizophrenia
- Any reported history from patient, family, or on supplied chart review or current
suicide risk
- Cohort D - Diagnosis of a dementia-related CNS disease other than AD (eg, Parkinson's
Disease, Huntington's Disease, frontotemporal dementia, multi-infarct dementia,
dementia with Lewy bodies, normal pressure hydrocephalus)
- Reported past or intended use of over-the-counter or prescription medication including
herbal medications within 7 days prior to dosing. Specific medications listed in
Section Concomittant Therapy may be allowed.
- Reported treatment with biologic agents (such as monoclonal antibodies including
marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
- Current enrollment or past participation within the last 30 days before signing of
consent in any other clinical study involving an investigational study intervention or
any other type of medical research.
- Alanine transaminase (ALT) or aspartate transaminase (AST) >1.5 x upper limit of
normal (ULN)
- Total bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if total
bilirubin is fractionated and direct bilirubin <35%)
- QTcF >450 msec for male participants or >470 msec for female participants
- Positive prestudy drug/alcohol screen
- Positive HIV antibody test
- Clinical laboratory findings outside the normal range and determined by the
investigator or medical monitor to be clinically significant.
- Clinically significant abnormalities on screening EEG which may indicate an increased
risk of seizure liability.
- Reported sensitivity to any of the study interventions, or components thereof, or drug
or other allergy that, in the opinion of the investigator or medical monitor,
contraindicates participation in the study
- Reported regular use of known drugs of abuse within the past 3 years.
- Presence of any contraindication to venous blood sampling for pharmacokinetic
analyses.
- Positive SARS-CoV-2 test or hepatitis panel (including hepatitis B surface antigen
[HBsAg] or hepatitis C virus antibody [anti-HCV]), or a positive HIV antibody screen
- Legal incapacity or limited legal capacity
- Participation in a clinical trial within 30 days prior to product administration.
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