A Single Site, Open Label, 4-inhalation Session, Explorative Clinical Investigation to Investigate the Ability of PreciseInhale to Direct Regional Lung Targeting and Reduce the Degree of Throat Deposition and Subsequent Gastrointestinal Absorption in Healthy Volunteers After Inhalation of Test Drug Substances Via the PreciseInhale System
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Tmax
研究概览
简要总结
This is a single site, open label, 4-inhalation sessions, explorative clinical investigation to investigate the ability of PreciseInhale to direct regional lung targeting and reduce the degree of throat deposition and subsequent gastrointestinal absorption of test drug substances in healthy volunteers after inhalation of test drug substances via the PreciseInhale system.
The study will include a screening visit, 8 consecutive treatment visits and a follow-up telephone call 3-5 days after the last inhalation session. There will be a screening period of up to 35 days and an at least 1-week washout between treatments.
详细描述
Intended use The PreciseInhale system is a benchtop aerosol generation and dispensation system set up for extracting aerosol from clinical inhalers. The PreciseInhale system is classified as a Class IIa device according to MDD Annex IX, Rule 11.
PreciseInhale is intended to administer test drug substances in precise doses by producing exact amounts of inhalable aerosols from a clinical inhaler.
Extraction of the aerosol and exposure to humans must comply with operator and test subject safety regulations and only conducted in accordance with permits from the Swedish Medical Products Agency (MPA) and Swedish Ethical Review Authority (SERA) if necessary.
Indication PreciseInhale is not intended to treat any specific condition that requires medical attention. The purpose of the clinical investigation is to prove that the principle of operation of PreciseInhale is useful for administration of aerosols to humans.
Methodology Screening (Visit 1) will take place from Day -35 to Day 1 and will include general health assessments and an eligibility check.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Device Feasibility
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 30 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and able to give written informed consent for participation in the study.
- •Healthy male or female subject aged ≥18 and ≤30 years inclusive.
- •Body Mass Index (BMI) ≥18 and ≤30 kg/m2 and weight ≥50 kg to ≤100 kg at screening.
- •Clinically normal medical history, physical findings, vital signs and laboratory values at the time of screening, as judged by the Investigator.
排除标准
- •History of any clinically significant disease or disorder (including clinically significant disease affecting the respiratory tract, thoracic deformities affecting lung function and/or lung volumes, muscle diseases affecting lung function and/or lung volumes and any known mouth or nasal passage deformities) which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- •Any clinically significant illness, medical/surgical procedure or trauma within two weeks prior to the first inhalation with the investigational device, which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- •Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV).
- •After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges:
- •Systolic blood pressure > 140 mm Hg
- •Diastolic blood pressure > 90 mm Hg
- •Pulse < 40 or > 85 beats per minute
- •Former regular daily smoker.
- •Current smokers or users of nicotine products (including vaping/e-cigarettes). Irregular use of nicotine (e.g. smoking, snuffing, chewing tobacco, vaping) less than three times per week is allowed before the screening visit.
- •FVC or FEV1 outside of normal ranges (depending on subject's gender, height and age) at screening.
- •Female subjects who are pregnant or who are currently breast feeding.
- •Administration of a new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment with less than one month before the first inhalation session.
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity (including pollen allergy), as judged by the Investigator.
- •History of hypersensitivity to drugs with a similar chemical structure or class to fluticasone or salmeterol, as judged by the Investigator.
- •Positive screen for drugs of abuse or alcohol at screening or on admission to the research unit prior to any of the inhalation sessions.
- •Current or history of alcohol abuse and/or use of anabolic steroids or drugs of abuse.
- •Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening.
- •Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.
结局指标
主要结局
Tmax
时间窗: From pre-dose to up to 24 hours post-dose
Time to Cmax. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations of salmeterol and fluticasone propionate after administration of the test drug substances via the Evohaler or the PreciseInhale-device will be collected.Tmax (in plasma) will be compared for PreciseInhale versus inhalation directly from pMDI (Evohaler). Outcome measured in session 1-4.
Correlation between two outcomes: AUC (weight-adjusted) -inhaled/exhaled dose
时间窗: AUC from pre-dose to up to 24 hours post-dose. Inhaled/exhaled dose collected post-dose at one occasion.
Area under the curve from time 0 to time t adjusted for weight and correlated to inhaled/exhaled dose. Outcome measured in session 2-4.
Actual number of inhalations
时间窗: Collected during inhalation session, approx. for 5 min
Measure air flow rates and aerosol concentration- and timing in the ventilation manoeuvre to demonstrate that regional targeting can be achieved with PreciseInhale bolus-breath hold method (data collected from inhalation sessions No 3 and 4). Outcome measured in session 3-4.
Cmax
时间窗: From pre-dose to up to 24 hours post-dose.
Maximum plasma concentration. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations of salmeterol and fluticasone propionate after administration of the test drug substances via the Evohaler or the PreciseInhale-device will be collected. Cmax (in plasma) will be compared for PreciseInhale versus inhalation directly from pMDI (Evohaler). Outcome measured in session 1-4.
AUC0-t
时间窗: From pre-dose to up to 24 hours post-dose
Area under the curve from time 0 to time t. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations of salmeterol and fluticasone propionate after administration of the test drug substances via the Evohaler or the PreciseInhale-device will be collected. AUC0-t (in plasma) will be compared for PreciseInhale versus inhalation directly from pMDI (Evohaler). AUC0-t (in plasma) will be compared for PreciseInhale versus inhalation directly from pMDI (Evohaler). Outcome measured in session 1-4.
Air flow rate
时间窗: Collected during inhalation session, approx. for 5 min
Measure air flow rates and aerosol concentration- and timing in the ventilation manoeuvre to demonstrate that regional targeting can be achieved with PreciseInhale bolus-breath hold method (data collected from inhalation sessions No 3 and 4). Outcome measured in session 3-4
Acutal bolus volume
时间窗: Collected during inhalation session, approx. for 5 min
Measure air flow rates and aerosol concentration- and timing in the ventilation manoeuvre to demonstrate that regional targeting can be achieved with PreciseInhale bolus-breath hold method (data collected from inhalation sessions No 3 and 4). Outcome measured in session 3-4.
Aerosol concentration
时间窗: Collected during inhalation session, approx. for 5 min
Measure air flow rates and aerosol concentration- and timing in the ventilation manoeuvre to demonstrate that regional targeting can be achieved with PreciseInhale bolus-breath hold method (data collected from inhalation sessions No 3 and 4). Outcome measured in session 3-4.
Chase air volume
时间窗: Collected during inhalation session, approx. for 5 min
Measure air flow rates and aerosol concentration- and timing in the ventilation manoeuvre to demonstrate that regional targeting can be achieved with PreciseInhale bolus-breath hold method (data collected from inhalation sessions No 3 and 4). Outcome measured in session 3-4.
Inhaled and exhaled dose, fraction inhaled/exhaled dose
时间窗: Collected post-dose at one occasion, approx. for 2 min
Calculated inhaled dose (µg), dose in exhaled air (µg) and fraction inhaled/exhaled dose (analysed from PARI filter, data collected from inhalation sessions No. 2, 3 and 4). Outcome measured in session 2-4.
次要结局
- Adverse events (AEs)(From start of first inhalation training until the end-of- study visit, an average of 5 weeks.)
- Number of changes in vital signs judged as clinically significant by Principal Investigator(Vital signs will be checked at pre-defined timepoints from the screening visit until the end-of-study visit, an average of 6 weeks)
- Number of changes in electrocardiogram (ECG) judged as clinically significant by Principal Investigator(ECG will be checked at pre-defined timepoints from the screening visit until the end-of-study visit, an average of 6 weeks)
- Device user experience questionnaire completed by PreciseInhale operator(Completed once after treatment period 4 (visit 8), approximately 15 min)
- Device user experience questionnaire completed by study subject(Completed once after treatment period 4 (visit 8), approximately 15 min)
- Device deficiencies (DD)(From start of first inhalation training until the end-of- study visit, an average of 5 weeks)
- Number of changes in safety laboratory parameters judged as clinically significant by Principal Investigator(Blood samples will be collected at pre-defined timepoints from the screening visit until the end-of-study visit, an average of 6 weeks)
- Number of changes in physical examination judged as clinically significant by Principal Investigator(Physical examination will be performed at pre-defined timepoints from the screening visit until the end-of- study visit, an average of 6 weeks)