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