A Single Dose Two-way Cross-over Study in Healthy Participants to Compare the Pharmacokinetics (PK) of Salbutamol Administered Via Metered Dose Inhalers Containing Propellants HFA-152a and HFA-134a
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-time Curve up to 30 Minutes Post-dose (AUC (0-30 Min)) of Salbutamol
研究概览
简要总结
This study will be conducted to compare the PK of salbutamol administered via metered dose inhalers (MDI) containing propellants 1,1-difluroethane (HFA-152a) and 1,1,1,2-tetrafluoroethane (HFA-134a) in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This will be a double-blind study.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 18 to 55 years, inclusive, at screening
- •Body mass index 18.0 to 30.0 kilograms per meter square (kg/m^2), inclusive, at screening
- •Weight: greater than or equal to (>=)50 kg
- •At screening, females must not be pregnant or lactating, or of non-childbearing potential
- •Female participants of childbearing potential who have a fertile male sexual partner must agree to use adequate contraception
- •Male participants, if not surgically sterilized, must agree to use adequate contraception
- •Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, electrocardiogram, and vital signs, as judged by the investigator
- •Willing and able to sign the informed consent form
排除标准
- •History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data
- •History or presence of any form of asthma, including childhood asthma and exercise induced asthma
- •Current enrollment or past participation in this clinical study
- •Participants with clinically significant abnormalities
- •A positive pre-study drug/alcohol screen or a history (or suspected history) of alcohol misuse or substance abuse
- •Positive nasopharyngeal polymerase chain reaction test for severe acute respiratory syndrome-corona virus type 2 (SARS-CoV-2) on Day -1 or any known close contact with a person who tested positive for SARS-CoV-2 or with a coronavirus disease 2019 participant within 2 weeks prior to admission
- •Impairment which would prevent the correct and consistent use of an MDI, as determined by the investigator
研究组 & 干预措施
Salbutamol HFA-152a MDI followed by Salbutamol HFA-134a MDI
Participants will receive Salbutamol HFA-152a MDI in treatment period 1 followed by Salbutamol HFA-134a MDI in treatment period 2. There will be a minimum washout period of 72 hours between each treatment period.
干预措施: Salbutamol HFA-152a (Drug)
Salbutamol HFA-152a MDI followed by Salbutamol HFA-134a MDI
Participants will receive Salbutamol HFA-152a MDI in treatment period 1 followed by Salbutamol HFA-134a MDI in treatment period 2. There will be a minimum washout period of 72 hours between each treatment period.
干预措施: Salbutamol HFA-134a (Drug)
Salbutamol HFA-134a MDI followed by Salbutamol HFA-152a MDI
Participants will receive Salbutamol HFA-134a MDI in treatment period 1 followed by Salbutamol HFA-152a MDI in treatment period 2. There will be a minimum washout period of 72 hours between each treatment period.
干预措施: Salbutamol HFA-152a (Drug)
Salbutamol HFA-134a MDI followed by Salbutamol HFA-152a MDI
Participants will receive Salbutamol HFA-134a MDI in treatment period 1 followed by Salbutamol HFA-152a MDI in treatment period 2. There will be a minimum washout period of 72 hours between each treatment period.
干预措施: Salbutamol HFA-134a (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve up to 30 Minutes Post-dose (AUC (0-30 Min)) of Salbutamol
时间窗: Pre-dose and post dose 3, 5, 10, 15, 20 and 30 minutes on Day 1 and Day 4
Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.
AUC From Time 0 to Infinity (AUC[0-inf]) of Salbutamol
时间窗: Pre-dose and post dose 0.05, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours on Day 1 and Day 4
Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.
AUC From Time 0 to Time t (AUC[0-t]) of Salbutamol
时间窗: Pre-dose and post dose 0.05, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours on Day 1 and Day 4
Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.
Maximum Observed Plasma Concentration (Cmax) of Salbutamol
时间窗: Pre-dose and post dose 0.05, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours on Day 1 and Day 4
Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.
次要结局
- Time to Cmax (Tmax) of Salbutamol(Pre-dose and post dose 0.05, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours on Day 1 and Day 4)
- Apparent Terminal Phase Half-life (t1/2) of Salbutamol(Pre-dose and post dose 0.05, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours on Day 1 and Day 4)
- Minimum Observed Serum Potassium Level (Emin, K) After Dosing of Salbutamol(0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4))
- Weighted Mean Serum Potassium (0-4 Hour) (AUEC, K)(Pre-dose and 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4))
- Maximum Observed Heart Rate (Emax, HR) After Dosing of Salbutamol(0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4))
- Weighted Mean Heart Rate (0-4 Hour) (AUEC, HR)(Pre-dose and 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4))
- Maximum Observed QTcF (Emax, QTcF) After Dosing of Salbutamol(0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4))
- Weighted Mean QTcF (0-4 Hour) (AUEC, QTcF)(Pre-dose and 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to 5 days)
- Absolute Values of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and Corrected QT (QTc) Interval(Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4)
- Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTc Interval(Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4)
- Absolute Values of ECG Parameter: Heart Rate(Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4)
- Change From Baseline in ECG Parameters: Heart Rate(Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4)
- Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet Count(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values of Hematology Parameter: Red Blood Cell (RBC) and Reticulocytes Count(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values of Hematology Parameter: Mean Corpuscular Volume (MCV)(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values of Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values of Hematology Parameter: Hemoglobin(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values of Hematology Parameter: Hematocrit(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values of Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Phosphokinase (CPK)(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values of Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values of Clinical Chemistry Parameter: Total Protein(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values for Chemistry Parameters: Calcium, Sodium, Potassium, Blood Urea Nitrogen (BUN)(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values for Chemistry Parameter: Glucose(Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4)
- Number of Participants With Urinalysis Parameters by Dipstick Method(On Day -1 (admission) and Day 5 (Discharge))
- Absolute Values of Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)(Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4)
- Absolute Values of Pulse Rate(Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4)