Randomized I/II Phase Study of ALZT-OP1 Combination Therapy in Alzheimer's Disease and Normal Healthy Volunteers

• Status: Completed
• Trial end date: 2021-01-18
• Target enrollment: 0
• Participant gender: All

Summary

This is a randomized, open-label, cross-over, pharmacokinetic and pharmacodynamic PK/PD study. (Part A)The PK portion of the study is designed to evaluate the pharmacokinetics of ALZT-OP1 (a combination drug therapy) designated as ALZT-OP1a and ALZT-OP1b, in both plasma and CSF, following co-administration of the two active investigational products, in healthy volunteers and Alzheimer subjects aged 55-79 and in good health. (Part B) The PD portion of the study will evaluate the pharmacodynamics of ALZT- OP1, using both plasma and CSF biomarkers, following 60 days of consecutive daily treatment, in AD subjects only.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: AZTherapies, Inc.
• Treatments: Cromolyn Sodium; Ibuprofen

Criteria

Inclusion Criteria:

• For All Subjects

1. Provide a signed written informed consent;

2. Age 55-79 old (inclusive);

3. ECG without abnormal, clinically significant findings;

4. Body mass index (BMI) ≥ 18 kg/m2 and ≤ 30 kg/m2

5. Negative urine drug screen for selected drugs of abuse at screening;

6. Negative for hepatitis and HIV at screening;

7. Negative for COVID-19 at screening;

8. Good general health, as determined by medical history, physical examination, and clinical laboratory testing;

9. Must provide written informed consent for CSF sampling. For AD Subjects Only

In addition to satisfying all of the above inclusion criteria, AD subjects must also meet the following criteria:

10. Diagnosed with mild to moderate Alzheimer's disease;

11. Clinical Dementia Rating (Global) 0.5

12. Mini-mental state examination (MMSE) ≤ 22;

13. Must be fluent in the language of the cognitive testing material being administered;

14. Stability of permitted medications for 4 weeks prior to study start;

15. Visual and auditory acuity adequate for neuropsychological testing.

16. Must provide written informed consent for APOe4 genotype testing; For All Subjects in Part A (PK)

17. Willingness to stay in the unit overnight for the duration of the PK portion of the study.

Exclusion Criteria:

• For All Subjects

1. Current smokers, or ex-smokers with a remote history (> 100 pack/year);

2. Clinically significant medical conditions;

3. History of abnormal clinically significant ECG abnormalities;

4. Symptomatic viral infection, or suspicion thereof (including rhinitis) in the last 14 days prior to dosing;

5. Signs of active pulmonary infection or other pulmonary inflammatory conditions, even in absence of febrile episodes, in the last 14 days;

6. History or presence of disease in the kidneys and/or heart, lungs, liver, gastrointestinal tract, endocrine organs or other conditions such as metabolic disease known to interfere with the absorption, distribution, metabolism, and excretion of drugs;

7. Malignancy, regardless of location;

8. Autoimmune disorders such as (but not limited to) lupus erythematosus, multiple sclerosis, rheumatoid arthritis, or sarcoidosis;

9. Investigational agents are prohibited one month prior to entry and for the duration of the trial;

10. Currently taking medications known to be CYP2C9 inducers (e.g., carbamazepine and rifampicin;

11. Currently taking cromolyn, or have taken cromolyn products, within the past 30 days;

12. Non-steroidal anti-inflammatory drug (NSAID) use (products containing ibuprofen while on study);

13. Allergy or hypersensitivity to cromolyn (also known as Intal®, Nasalcrom®, Opticrom®, Gastrocrom®, etc.);

14. Allergy or hypersensitivity to ibuprofen (Advil®, Motrin®, Nuprin®, etc.) or aspirin, including Stevens-Johnson syndrome;

15. History of hypersensitivity or allergies to any of the drug compound under investigation (cromolyn sodium, ibuprofen, lactose, or magnesium stearate);

16. Current respiratory disorders and chronic respiratory disease with impaired respiratory effort or difficulty taking inhaled drugs (examples: COPD, emphysema);

17. Abnormal pulmonary function test, defined for this protocol as: FEV1 < 70% of predicted value, indicating moderate or severe respiratory impairment;

18. Any other disease or condition, which, in the opinion of the investigator, would make the subject unsuitable for this study;

19. Female subjects of reproductive potential with a positive pregnancy test (urine or serum) or who are pregnant or lactating.

For AD Subjects Only

In addition to not meeting any of the above exclusion criteria for Normal Healthy Volunteers, AD subjects must also not meet any of the following criteria:

20. Any significant neurological disease other than suspected incipient AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities;

21. Major depressive episode, as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) within the past 6 months, which could lead to difficulty complying with the protocol;

22. History of schizophrenia or bipolar disorder (DSM-V criteria);

23. Currently taking medications that could lead to difficulty complying with the protocol; For All Subjects in Part A (PK)

24. Aspirin, or products containing aspirin, while on PK study; For All Subjects in Part B (PD)

25. Chronic daily use of aspirin exceeding standard of care guidelines for low dose aspirin therapy for prevention of stroke and/or other recommended uses, while on PD study.