A Randomized, Double-blind, Placebo-controlled, Two-way Crossover 7-day Study to Investigate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Repeat Dose Inhaled GW642444 25 μg (Micrograms) in Children Aged 5-11 Years With Persistent Asthma.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 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 investigate the effect of dosing paedeatric asthmatic subjects with GW642444, an orally inhaled long-acting agonist of the β2-adrenoceptor.
详细描述
This study will investigate the effect of dosing with 25 μg GW642444, an orally inhaled long-acting agonist of the β2-adrenoceptor, in asthmatic subjects aged 5 to 11. GW642444 is currently under development as the long-acting beta-agonist component of a combination product containing an inhaled corticosteroid and a longacting beta-agonist.
Subjects will receive a single dose via a novel dry powder inhaler, then 7 days once-daily repeat dosing following a washout period. The study will be a randomized two-way crossover, with a placebo control. Approximately 26 subjects will be recruited to this study, with the aim that 20 will complete the study. Safety, tolerability, pharmacokinetics and glucose and potassium levels will be investigated.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 5 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and pre-menarchial female subjects aged 5-11 years on the last planned treatment day are eligible for this study. Pre-menarchial females are defined as any female who has yet to begin menses and is considered Tanner Stage 2 or less.
- •Diagnosis of asthma at least 6 months prior to screening.
- •Patients must be controlled on their existing asthma treatment at Screening as defined by a Childhood Asthma Control Test score of >19 and PEF (Peak Expiratory Flow) >75 % predicted.
- •Subjects must be taking a stable regimen of fluticasone propionate (≤200 μg (micrograms) twice daily or equivalent) and short acting beta-agonist inhaler on an as-need basis for at least 4 weeks prior to screening.
- •Apart from asthma, eczema and rhinitis, subjects should be healthy and suffer from no other significant medical conditions.
- •Subjects must weigh at least 15 kg (kilograms).
- •Subjects must demonstrate ability to accept and effectively use the GW642444 device using the demonstration kits provided to the site.
- •The subject and parent or guardian are able to understand and comply with protocol requirements, instructions, and protocol-stated restrictions. The parent or guardian must have the ability to read, write and record diary information collected throughout the study. The parent or guardian must also have the ability to manage study drug administration and PEF assessments.
- •At least one parent or guardian has signed and dated the written informed consent prior to admission to the study. This will be accompanied by informed assent from the subject.
排除标准
- •Subjects currently receiving (or have received within 4 weeks of screening) any of the following asthma therapies: theophyllines, long-acting inhaled beta-agonists, oral beta-agonist.
- •Subjects who have changed their asthma medication within 4 weeks of screening.
- •Clinical visual evidence of oral candidiasis at screening.
- •Any clinically relevant abnormality identified on the screening medical assessment
- •Any medical condition or circumstance making the subject unsuitable for participation in the study (e.g. history of life-threatening asthma)
- •Asthma exacerbation requiring systemic corticosteroids (oral, intramuscular, intravenous) or Emergency Room attendance within 3 months or asthma exacerbation requiring hospitalization within 6 months prior to the screening visit.
- •Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract which is not resolved within 4 weeks of the screening visit.
- •Any adverse reaction including immediate or delayed hypersensitivity to any betaagonist therapy.
- •Known or suspected sensitivity to the constituents of the novel dry powder inhaler (i.e., lactose or magnesium stearate), for example, history of severe milk protein allergy.
- •The parent or guardian has history of psychiatric disease, intellectual deficiency, substance abuse, or other condition (e.g., inability to read, comprehend or write) which will limit the validity of consent to participate in this study.
- •A subject will not be eligible for this study if he/she is an immediate family member of the participating Investigator, sub-Investigator, study coordinator, or employee of the participating Investigator.
- •Children who are wards of the state or government.
- •Evidence of clinically significant abnormality in the 12-lead ECG (electrocardiogram) at Screening
研究组 & 干预措施
COHORT 1 (RANDOMISATION AB or BA)
8-11 years old; Subjects will be assigned to receive GW642444 25μg or matching placebo (in a 1:1 ratio) in an AB or BA (A= GW64244, B= Placebo) sequence.
Following randomisation (AB or BA) subjects will receive a single dose treatment, followed by 7 day washout period. This will then be followed by a repeat dose session of the same treatment (Day 8 and Day 14 in house, Days 9-13 at home).
Each subject will then complete the same sequence for the alternative treatment in the second session. There will be a washout period of at least 7 days between the treatment periods.
干预措施: GW642444 (Drug)
COHORT 1 (RANDOMISATION AB or BA)
8-11 years old; Subjects will be assigned to receive GW642444 25μg or matching placebo (in a 1:1 ratio) in an AB or BA (A= GW64244, B= Placebo) sequence.
Following randomisation (AB or BA) subjects will receive a single dose treatment, followed by 7 day washout period. This will then be followed by a repeat dose session of the same treatment (Day 8 and Day 14 in house, Days 9-13 at home).
Each subject will then complete the same sequence for the alternative treatment in the second session. There will be a washout period of at least 7 days between the treatment periods.
干预措施: Placebo (Drug)
COHORT 2 (RANDOMISATION AB or BA)
5-7 years old. Subjects will be assigned to receive GW642444 25μg or matching placebo (in a 1:1 ratio) in an AB or BA (A= GW64244, B= Placebo) sequence.
Following randomisation (AB or BA) subjects will receive a single dose treatment, followed by 7 day washout period. This will then be followed by a repeat dose session of the same treatment (Day 8 and Day 14 in house, Days 9-13 at home).
Each subject will then complete the same sequence for the alternative treatment in the second session. There will be a washout period of at least 7 days between the treatment periods.
干预措施: GW642444 (Drug)
COHORT 2 (RANDOMISATION AB or BA)
5-7 years old. Subjects will be assigned to receive GW642444 25μg or matching placebo (in a 1:1 ratio) in an AB or BA (A= GW64244, B= Placebo) sequence.
Following randomisation (AB or BA) subjects will receive a single dose treatment, followed by 7 day washout period. This will then be followed by a repeat dose session of the same treatment (Day 8 and Day 14 in house, Days 9-13 at home).
Each subject will then complete the same sequence for the alternative treatment in the second session. There will be a washout period of at least 7 days between the treatment periods.
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 start of study medication until Week 11 (Visit 8)/Early Withdrawal
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 AE/SAE module for a complete list of AEs and SAEs.
Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 49)
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelets, and white blood cell (WBC) count at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 49)
Blood samples were collected for the measurement of hemoglobin and MCHC at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 49)
Blood samples were collected for the measurement of reticulocytes and RBCs at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Hematocrit Value at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 49)
Blood samples were collected for the measurement of hematocrit at Day 14 of the respective treatment period. Hematocrit is a measure of the percentage of the volume of the whole blood that is composed of red blood cells, as determined by separation of red blood cells from the plasma (usually by centrifugation). Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 49)
Blood samples were collected for the measurement of MCV at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Mean Corpuscle Hemoglobin (MCH) Value at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 49)
Blood samples were collected for the measurement of MCH at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 49)
Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Albumin and Total Protein Values at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 49)
Blood samples were collected for the measurement of albumin and total protein at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 49)
Blood samples were collected for the measurement of calcium, chloride, carbon dioxide content/bicarbonate (CO2/BI), glucose, potassium, sodium, and urea/BUN at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 49)
Blood samples were collected for the measurement of total bilirubin, direct bilirubin, creatinine, and uric acid at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Peak Expiratory Flow on Day 1, Day 8, and Day 14 of the Respective Treatment Period
时间窗: Day 1, Day 8, and Day 14 of the respective treatment period (up to Study Day 49)
Peak Expiratory Flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF is calculated as the maximum of three readings taken at each timepoint for each participant. Baseline is defined as the pre-dose measurement at Day 1 for the respective period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1, Day 8, and Day 14 of the Respective Treatment Period
时间窗: Day 1, Day 8, and Day 14 of the respective treatment period (up to Study Day 49)
SBP and DBP were measured at Day 1, Day 8, and Day 14 of the respective treatment period. PD=post-dose. Baseline is defined as the pre-dose measurement at Day 1 for the respective period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
Maximum Heart Rate at Day 1 and Day 14 of the Respective Treatment Period
时间窗: Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
Heart rate (HR) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
Weighted Mean Heart Rate at Day 1 and Day 14 of the Respective Treatment Period
时间窗: Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
Heart rate (HR) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Weighted means were derived using the linear trapezoidal rule. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative times were used for these observations. For 0-8 hr parameters, treatment, period, participant Baseline, and period Baseline were fitted as fixed effects, and participant was fitted as a random effect. For 0-2 hr parameters, treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
Maximum QTcF at Day 1 and Day 14 of the Respective Treatment Period
时间窗: Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
The electrocardiographic (ECG) parameter QT duration corrected using Fridericia's formula (QTcF) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. For 0-8 hr parameters, treatment, period, participant Baseline, and period Baseline were fitted as fixed effects, and participant was fitted as a random effect. For 0-2 hr parameters, treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
Weighted Mean QTcF at Day 1 and Day 14 of the Respective Treatment Period
时间窗: Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
The electrocardiographic (ECG) parameter QT duration corrected using Fridericia's formula (QTcF) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative times were used for these observations. For 0-8 hr parameters, treatment, period, participant Baseline, and period Baseline were fitted as fixed effects, and participant was fitted as a random effect. For 0-2 hr parameters, treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
次要结局
- AUC(0-t) and AUC(0-8) on Day 14 of the Respective Treatment Period(Day 14 of the respective treatment period (up to Study Day 49))
- Cmax on Day 14 of the Respective Treatment Period(Day 14 of the respective treatment period (up to Study Day 49))
- Tmax, t1/2, and t at Day 14 of the Respective Treatment Period(Day 14 of the respective treatment period (up to Study Day 49))
- Blood Glucose and Potassium on Day 14 of the Respective Treatment Period(Day 14 of the respective treatment period (up to Study Day 49))
- Average Oropharyngeal Cross-sectional Area on Day 1 and Day 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period (up to Study Day 49))
- Distance of Assessment on Day 1 and Day 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period (up to Study Day 49))
- Oropharyngeal Volume on Day 1 and Day 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period (up to Study Day 49))
- Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Day 1 and Day 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period (up to Study Day 49))
- Inhalation Time on Day 1 and Day 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period (up to Study Day 49))
- Inhaled Volume on Day 1 and Day 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period (up to Study Day 49))
- Peak Pressure Drop on Day 1 and Day 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period (up to Study Day 49))
- Total Emitted Dose (TED) on Day 1 and Day 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period (up to Study Day 49))
- Ex-throat Dose (ETD) and ETD <2 Microns on Day 1 and Day 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period (up to Study Day 49))