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).
Mast cell stabilizer
The inhaler will be used to deliver ALZT-OP1a via oral inhalation for both days on study.
12 subjects will receive a single oral inhaled dose of ALZT-OP1a, via dry powder inhaler, and a single oral tablet dose of ALZT-OP1b on Day 1, and two doses of ALZT-OP1a and ALZT-OP1b on Day 2, within two minutes of each other. All subjects will have plasma collected for PK analysis and 6 of 12 consented subjects from this group will provide CSF samples for analysis. CSF collected on Day 1 only.
12 subjects will receive two oral inhaled doses of ALZT-OP1a, via dry powder inhaler, and two oral tablet doses of ALZT-OPb, within two minutes of each other, on Day 1, and single doses of ALZT-OP1a and ALZT-OP1b on Day 2. All subjects will have plasma collected for PK analysis and 6 of 12 consented subjects from this group will provide CSF samples for analysis. CSF collected on 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.