Phase 1 Study of ALZT-OP1 Combination Therapy in Normal Healthy Volunteers

A Phase I, Randomized, Open-Labeled Pharmacokinetic Study of ALZT-OP1 in Normal Healthy Volunteers

This is an open-labeled, cross-over design, pharmacokinetic study, to determine 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 active compounds, in healthy volunteers, aged 55-75, and in good general health.

This is an open-labeled, cross-over design, pharmacokinetic study, where 24 subjects will be randomly assigned to receive treatment regimen A-B or B-A on two consecutive days of dosing.

Two dosing groups are planned for the study :

• Group 1 (n=12)
• Group 2 (n=12)

Each group will be admitted to the Phase I Unit the evening before dosing and will initiate dosing the next morning for 2-days of consecutive treatment (A-B, or B-A). Both groups will undergo identical study related procedures, except those subjects that consent to CSF collection on Day 1 of dosing.

Dose regimen A consists of a single inhaled oral dose of ALZT-OP1a via dry powder inhaler + a single oral tablet dose of ALZT-OP1b.

Dose regimen B consists of two oral inhaled doses of ALZT-OP1a, not more than 2 minutes apart, via dry powder inhaler + two oral tablet doses of ALZT-OP1b.

Plasma Collection, All Subjects (n=24) 1 mL blood samples will be collected at T: 0, 5, 10, 15, 30, 1 hr, 2 hr, 4 hr, and 6 hours, following ALZT-OP1 administration (Days 1 and 2).

CSF Collection, Sub-group (n=12) A sub-group of 12 subjects will be consented for CSF collection.

1 mL of CSF will be collected at T: 0, 5 min, 30 min, 2 hr, and 4 hours, following ALZT-OP1 administration (Day 1 only).

Inclusion Criteria:

• Provide a signed written informed consent;
• Age 55-75 inclusive;
• ECG within normal limits;
• Body mass index (BMI) ≥ 18 kg/m2 and ≤ 30 kg/m2;
• Negative urine drug screen for selected drugs of abuse at screening;
• Negative for hepatitis and HIV at screening;
• Good general health, as determined by medical history, physical examination, and clinical laboratory testing;
• Willingness to stay in the unit overnight for the duration of the study;
• Consent for CSF collection (for those in CSF group).

Exclusion Criteria:

• Current smokers, or ex-smokers with a remote history (> 100 pack/year);
• Clinically significant medical conditions;
• History of ECG abnormalities;
• Symptomatic viral infection, or suspicion thereof (including rhinitis) in the last 14 days prior to dosing;
• Signs of active pulmonary infection or other pulmonary inflammatory conditions, even in absence of febrile episodes, in the last 14 days;
• 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;
• Malignancy, regardless of location;
• Autoimmune disorders such as (but not limited to) lupus erythematosus, multiple sclerosis, rheumatoid arthritis, or sarcoidosis;
• Investigational agents are prohibited one month prior to entry and for the duration of the trial;
• Currently taking medications known to be CYP2C9 inducers (i.e. carbamazepine and rifampicin);
• Currently taking cromolyn, or have taken cromolyn, within the past 30 days;
• NSAID use (products containing ibuprofen while on study);
• Aspirin, or products containing aspirin, while on study;
• Allergy or hypersensitivity to cromolyn (also known as Intal®, Nasalcrom®, etc.);
• Allergy or hypersensitivity to ibuprofen (Advil®, Motrin®, Nuprin®, etc.) or aspirin, including Stevens-Johnson syndrome;
• History of hypersensitivity or allergies to any of the drug compound under investigation (cromolyn, ibuprofen, lactose, or magnesium stearate);
• History of clinically significant respiratory disorders and chronic respiratory disease with impaired respiratory effort or difficulty taking inhaled drugs (examples: COPD, emphysema);
• Abnormal pulmonary function test, defined for this protocol as: FEV1/FVC < 70% of the predicted value for the subject, when compared to reference values; AND FEV1 and FVC < 70% of predicted value when compared to reference values, indicating moderate to severe respiratory obstruction;
• Any other disease or condition, which, in the opinion of the investigator, would make the subject unsuitable for this study;
• Female subjects of reproductive potential with a positive pregnancy test (urine or serum) or who are pregnant or lactating.