A Randomised, Single-dose, Dose Ascending, Double-blind, Placebo Controlled, Four-way, Incomplete Block Crossover Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled Doses of GW642444M With Magnesium Stearate in COPD Patients.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
研究概览
简要总结
This study will involve the use of a new compound, GW642444 that is being developed for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It works by acting on cells in the lungs, causing some of the muscles around the lungs to relax and open up better (bronchodilation), making breathing easier. When a medicine is made into a form ready to be given to patients, the active ingredient is often prepared in the form of a salt, and inactive ingredients (excipients) are often added. Inactive ingredients might be used to help a medicine work better, to make it easier to produce the medicine, or to make it easier to get an accurate dose of medicine. In previous studies the study drug has been given as a dry powder in the form of either the 'H' salt (with the excipient lactose), or in the form of the 'M' salt (with the excipients lactose and cellobiose octaacetate). In this study the 'M' salt form of the study drug has been prepared with lactose and a new excipient called magnesium stearate (instead of cellobiose octaacetate). Participants in this study will receive both the 'H' salt (GW642444H) and the new 'M' salt (GW642444M) containing magnesium stearate. This study will be the first time the new 'M' salt form of the study drug will be given to COPD patients.
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)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
GW642444M 25mcg
干预措施: GW642444M (Drug)
GW642444M 25mcg
干预措施: placebo (Drug)
GW642444M 50mcg
干预措施: GW642444M (Drug)
GW642444M 100mcg
干预措施: GW642444M (Drug)
GW642444M 100mcg
干预措施: placebo (Drug)
GW642444H 100mcg
干预措施: GW642444H (Drug)
GW642444H 100mcg
干预措施: placebo (Drug)
placebo
干预措施: placebo (Drug)
结局指标
主要结局
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
时间窗: From the first dose of the study medication until the Follow-up Visit (up to Study Day 60)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cell Count at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, and white blood cell (WBC) count at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of hemoglobin and MCHC at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Reticulocyte and Red Blood Cell (RBC) Count at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of reticulocyte and RBCs at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Hematocrit at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of hematocrit at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Mean Corpuscle Volume (MCV) at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of MCV at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Values at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of MCH at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK) and Gamma Glutamyl Transferase (GGT) Values at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Albumin and Total Protein at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of albumin and total protein at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Cholesterol, Chloride, Potassium, Sodium, Triglycerides, and Urea at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of cholesterol, chloride, potassium, sodium, triglycerides, and urea at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Total Bilirubin and Creatinine at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of total bilirubin and creatinine at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in C-reactive Protein at 24 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Blood samples were collected for the measurement of c-reactive protein at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over the Post-dose 24 Hour (h) Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
SBP and DBP were measured at Baseline and over the post-dose 24 h period at the following scheduled time points: 20 minutes (M), 45 M, 1h, 2h, 3h, 4h, 6h, and 24 h. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Heart Rate Over the Post-dose 24 Hour (h) Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
Heart rate (HR) was measured at Baseline and over the post-dose 24 h period at the following scheduled time points: 20 minutes (M), 45 M, 1 h, 2 h, 3 h, 4 h, 6 h, and 24 h. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
Change From Baseline in Electrocardiographic (ECG) Parameters Over the Post-dose 24 Hour (h) Period
时间窗: Baseline and Day 1 of each treatment period (up to Study Day 54)
ECG parameters \[PR, QRS, RR, QT (uncorrected), QTcB (QT corrected by Bazett's formula) and QTcF (QT corrected by Fridericia's formula) intervals\] were measured at Baseline and over the post-dose 24h period at the following scheduled time points: 20 minutes (min), 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, and 24 h. Baseline was defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.
次要结局
- Mean FEV1 Over 23 and 24 Hours After Dosing(Baseline and Day 1 of each treatment period (up to Study Day 54))
- Weighted Mean and Maximum Value (0 - 4 Hours) QTc(B) and QTc(F)(Baseline and Day 1 of each treatment period (up to Study Day 54))
- Weighted Mean and Maximum Value (0 - 4 Hours) Supine Heart Rate(Baseline and Day 1 of each treatment period (up to Study Day 54))
- Weighted Mean and Maximum Value (0 - 4 Hours) of Supine Systolic and Diastolic Blood Pressure(Baseline and Day 1 of each treatment period (up to Study Day 54))
- Weighted Mean and Maximum/Minimum Value (0 - 4 Hours) for Glucose and Potassium(Baseline and Day 1 of each treatment period (up to Study Day 54))
- AUC(0- t) and up to 1 Hour Post-dose (AUC[0-1]) of GW642444 and Its Metabolites GI179710, GW630200, and GSK932009, After a Single Dose of GW642444(Baseline and Day 1 of each treatment period (up to Study Day 54))
- Cmax of GW642444 and Its Metabolites GI179710, GW630200, and GSK932009, After a Single Dose of GW642444(Day 1 of each treatment period (up to Study Day 54))
- Tmax of GW642444 and Its Metabolites GI179710, GW630200, and GSK932009, After a Single Dose of GW642444(Day 1 of each treatment period (up to Study Day 54))