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
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).
- 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).
- 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
- 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.