Randomized Phase 1 Study of Safety, Pharmacokinetics, Segmental Lung Deposition, and Digital Validation of a Breath-Actuated EDDIS Inhalation Delivery System Using 99mTc-DTPA in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Segmental lung deposition of 99mTc-DTPA measured by planar gamma scintigraphy
研究概览
简要总结
Device:
EDDIS-IDDS (Enhanced Digital Dose Inhalation Delivery System) - a portable, breath-actuated, digitally monitored system for precision delivery of inhaled agents with automated recording of inspiratory volume, flow, duration, and breath-hold parameters.
Drug:
99mTc-DTPA (technetium-99m diethylenetriaminepentaacetic acid) - administered in aqueous solution (0.9% NaCl), radiolabeled for gamma scintigraphic imaging.
Total dose: 500-800 µCi in 2 ml solution.
Administration:
Single-dose inhalation under supervision in a clinical setting.
详细描述
This Phase 1, single-center, open-label clinical study is designed to evaluate the safety, pharmacokinetics, inhalation dynamics, segmental lung deposition, and digital monitoring capabilities of the breath-actuated EDDIS-IDDS (Enhanced Digital Dose Inhalation Delivery System) when used to deliver a radiolabeled aqueous formulation containing 99mTc-DTPA and a microdose of perfluorocarbon emulsion.
The investigational aerosol is administered via a digitally controlled inhalation system that automatically triggers delivery based on the patient's inspiratory effort. The system continuously records real-time parameters including tidal volume, inspiratory flow rate, inhalation duration, and breath-hold time. These data are securely transmitted and stored for analysis, enabling high-resolution correlation between inhalation patterns and lung deposition outcomes.
The radiolabel (99mTc-DTPA) is confined to the aqueous phase of the aerosol. The perfluorocarbon emulsion is included to simulate the aerodynamic behavior of complex liquid formulations and to evaluate their interaction with the lung architecture under controlled inhalation conditions. Radiolabeling is not applied to the perfluorocarbon phase, ensuring imaging specificity and avoiding nonspecific signal interference.
Imaging will be performed using planar gamma scintigraphy at 0, 15, and 30 minutes post-inhalation. Anterior and posterior projections will be acquired to allow quantitative segmental lung analysis. Measurements will include total deposition, central vs. peripheral distribution, and temporal sedimentation characteristics.
In parallel, blood samples will be collected at 1, 2, and 4 hours post-dose to determine systemic pharmacokinetics of the radiolabeled tracer. Urine samples collected at 4 hours will be used to calculate cumulative renal excretion. Adverse events, vital signs, and laboratory parameters will be monitored for 24 hours post-inhalation to assess tolerability and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
No masking will be applied. Participants, investigators, and outcomes assessors will be aware of the intervention, as this is a non-therapeutic, Phase 1 imaging and device validation study
入排标准
- 年龄范围
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 45 years
- •Healthy adults with no clinically significant medical history
- •Normal spirometry (FEV1 ≥ 80% predicted)
- •Body Mass Index (BMI) between 18.5 and 29.9 kg/m²
- •No prior exposure to radiopharmaceuticals in the past 12 months
- •Able and willing to comply with study procedures and provide written informed consent
- •Current or past use of tobacco products or electronic nicotine delivery systems (e.g., e-cigarettes) is not an exclusion criterion
排除标准
- •History of asthma, COPD, or other chronic respiratory conditions
- •History of lung surgery, pulmonary embolism, or interstitial lung disease
- •Any ongoing respiratory infection or fever ≥ 38.0°C at screening or study day
- •Uncontrolled or progressive arterial hypertension
- •Known cardiovascular disease (e.g., arrhythmia, ischemic heart disease, heart failure)
- •Presence of blood in saliva, hemoptysis, or any known pulmonary bleeding
- •Diagnosed pulmonary emphysema
- •Known coagulation disorders or use of anticoagulant therapy
- •History of hypersensitivity to perfluorocarbons, DTPA, or radiopharmaceutical agents
- •Prior exposure to radiopharmaceuticals within the last 12 months
- •Participation in another clinical trial within the last 60 days
- •Pregnancy or breastfeeding
- •Use of any investigational or prescription drug within 30 days prior to study drug administration
- •Any condition which, in the opinion of the investigator, would pose a health risk or interfere with study interpretation
研究组 & 干预措施
Single Inhalation of 99mTc-DTPA via EDDIS System
This arm includes all participants receiving a single inhaled dose of 99mTc-DTPA (radiolabeled aqueous solution in 0.9% NaCl, 2 ml total volume, 500-800 µCi), administered via the portable, breath-actuated EDDIS-IDDS (Enhanced Digital Dose Inhalation Delivery System).
The procedure includes real-time digital recording of inspiratory parameters and post-inhalation planar scintigraphic imaging at 0, 15, and 30 minutes to assess pulmonary deposition.
Pharmacokinetic samples (blood and urine) are collected for systemic exposure analysis. No control or comparator arm is included.
干预措施: Technetium-99m Diethylenetriaminepentaacetic Acid (Drug)
Single Inhalation of 99mTc-DTPA via EDDIS System
This arm includes all participants receiving a single inhaled dose of 99mTc-DTPA (radiolabeled aqueous solution in 0.9% NaCl, 2 ml total volume, 500-800 µCi), administered via the portable, breath-actuated EDDIS-IDDS (Enhanced Digital Dose Inhalation Delivery System).
The procedure includes real-time digital recording of inspiratory parameters and post-inhalation planar scintigraphic imaging at 0, 15, and 30 minutes to assess pulmonary deposition.
Pharmacokinetic samples (blood and urine) are collected for systemic exposure analysis. No control or comparator arm is included.
干预措施: EDDIS-IDDS (Enhanced Digital Dose Inhalation Delivery System) (Device)
结局指标
主要结局
Segmental lung deposition of 99mTc-DTPA measured by planar gamma scintigraphy
时间窗: Within 30 minutes post-inhalation
Quantitative analysis of 99mTc-DTPA distribution in lung segments using planar gamma scintigraphy imaging system with anterior/posterior views at 0, 15, and 30 minutes post-dose. Results expressed as percentage of total deposited dose per lung segment.
Incidence of treatment-emergent adverse events (TEAEs) assessed by clinical evaluation
时间窗: Within 24 hours post-inhalation
Number and severity of adverse events recorded after a single inhalation of 99mTc-DTPA via the EDDIS system, assessed through standardized clinical observation checklist, vital signs monitoring (blood pressure, heart rate, respiratory rate, temperature), and structured subject symptom reports using Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
次要结局
- Radioactivity concentration in venous blood samples measured using gamma counter to determine systemic absorption of inhaled 99mTc-DTPA over time. Results expressed as counts per minute per milliliter (cpm/mL)(Up to 4 hours post-dose (samples at 1, 2, and 4 hours))
- Cumulative urinary excretion of 99mTc-DTPA measured by gamma counter analysis(up to 4 hours post-dose)
- Digital accuracy of inspiratory parameter recording assessed by calibration comparison(During inhalation procedure (real-time measurement))
研究者
Andrey Petrov
Principal Investigator
Petrov, Andrey