A Phase I, Randomized, Open-Labeled Pharmacokinetic Study of ALZT-OP1 in Normal Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- ALZT-OP1a
- Conditions
- Healthy Volunteers
- Sponsor
- AZTherapies, Inc.
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Non-compartmental plasma pharmacokinetics for ALZT-OP1a and ALZT-OP1b
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
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.
Detailed Description
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).
Investigators
Eligibility Criteria
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);
Arms & Interventions
Treatment A-B
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.
Intervention: ALZT-OP1a
Treatment A-B
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.
Intervention: ALZT-OP1b
Treatment A-B
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.
Intervention: Dry Powder Inhaler
Treatment B-A
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.
Intervention: ALZT-OP1a
Treatment B-A
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.
Intervention: ALZT-OP1b
Treatment B-A
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.
Intervention: Dry Powder Inhaler
Outcomes
Primary Outcomes
Non-compartmental plasma pharmacokinetics for ALZT-OP1a and ALZT-OP1b
Time Frame: T=0 to 6 hours (0, 5, 10, 15, 30, 60, 120, 240, and 360 minutes)
* AUC (0-∞) (area under the curve from 0 to infinity) * AUC (0-t) (area under the curve from 0 to t hours where t is the last measured concentration * AUCPLASMA/AUCCSF (ratio at 5 min, 30 min, 2 hr and 4 hours) * CL/F (apparent total body clearance) * Cmax (maximum plasma concentration observed) * T ½ (half life) * Tmax (sampling time at which Cmax occurred) * Vd/F (apparent volume of distribution Plasma concentration-time profiles will be presented for both study drugs.
Secondary Outcomes
- Levels of ALZT-OP1a and ALZT-OP1b in cerebrospinal fluid (CSF)(T=0 to 4 hours (0, 5, 30, 120, and 240 minutes))
- Number of Treatment Emergent Adverse Events (TEAE)(2 days)