A Phase I, Randomized, Open-Labeled Pharmacokinetic Study of ALZT-OP1 in Normal Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Non-compartmental plasma pharmacokinetics for ALZT-OP1a and ALZT-OP1b
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: ALZT-OP1a (Drug)
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.
干预措施: ALZT-OP1b (Drug)
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.
干预措施: Dry Powder Inhaler (Device)
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.
干预措施: ALZT-OP1a (Drug)
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.
干预措施: ALZT-OP1b (Drug)
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.
干预措施: Dry Powder Inhaler (Device)
结局指标
主要结局
Non-compartmental plasma pharmacokinetics for ALZT-OP1a and ALZT-OP1b
时间窗: 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.
次要结局
- 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)