A Randomized, Double-blind, Placebo-controlled, Two-way Crossover 14-day Study to Investigate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Repeat Dose Inhaled Fluticasone Furoate 100ug (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
- 27
- 试验地点
- 1
- 主要终点
- Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period
研究概览
简要总结
This study will investigate the effect of dosing with flutucasone furoate in asthmatic subjects aged 5-11 years of age. A randomized, two-way crossover, with placebo control, over a 14 day treatment period, it will investigate safety, tolerability, pharmacokinetics and serum cortisol levels.
详细描述
This study will investigate the effect of dosing with fluticasone furoate 100 μg (micrograms) in asthmatic subjects aged 5-11 years of age. Fluticasone furoate is currently under development as the inhaled corticosteroid component of a combination product containing an inhaled corticosteroid and a long-acting beta-agonist.
The study will be a randomized two-way crossover, with a placebo control. During each treatment period subjects will receive a daily dose via a novel dry powder inhaler for 14 days. Approximately 26 subjects will be recruited to this study, with the aim that 20 will complete the study. Safety, tolerability, pharmacokinetics and serum cortisol 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) ≥80% predicted.
- •Apart from asthma, eczema and rhinitis, subjects should be healthy and suffer from no other significant medical conditions.
- •Subjects must be taking a stable regimen of a short acting beta-agonist inhaler on an as-need basis for at least 4 weeks prior to screening.
- •Subjects must weigh at least 15 kg (kilograms).
- •Subjects must demonstrate ability to accept and effectively use the fluticasone furoate devices using the demonstration kits provided to the site.
- •Subjects and parents/guardians must be able to understand and comply with protocol requirements, instructions and protocol-stated restrictions. Parents/guardians must have the ability to read, write and record diary information collected throughout the study. They must also have the ability to manage study drug administration and PEF assessments.
- •A signed and dated written informed consent from at least one parent/guardian, and accompanying informed assent from the subject prior to admission to the study.
排除标准
- •Subjects who have changed their asthma medication within 4 weeks of screening or subjects currently being treated with inhaled corticosteroids or have received such treatment within 4 weeks of screening. In addition, subjects currently receiving (or have received within 4 weeks of screening) any of the following asthma therapies: theophyllines, long-acting inhaled beta-agonists or oral beta-agonists.
- •Any medical condition or circumstance making the volunteer unsuitable for participation in the study (e.g. history of life-threatening asthma).
- •Any clinically relevant abnormality identified on the screening medical assessment, including 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 screening.
- •Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of screening and led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
- •Clinical visual evidence of oral candidiasis at screening.
- •Parent/guardian has history of psychiatric disease, intellectual deficiency, substance abuse, or other condition (e.g., inability to read, comprehend and write) which will limit the validity of consent to participate in this study.
- •Any adverse reaction including immediate or delayed hypersensitivity to any beta-2-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic corticosteroid 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.
- •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 A
(8-11 years old) Repeat dose session: Fluticasone furoate 100µg; Day 1 and Day 14 = in house dosing; Day 2-13 = home dosing
干预措施: Fluticasone furoate (Drug)
COHORT 1 RANDOMISATION B
(8-11 years old) Repeat dose session: matching placebo; Day 1 and Day 14 = in house dosing; Days 2-13 = home dosing
干预措施: Matching placebo (Drug)
COHORT 2 RANDOMISATION A
(5-7 years old) Repeat dose session: Fluticasone furoate 100µg; Day 1 and Day 14 = in house dosing; Days 2-13 = home dosing
干预措施: Fluticasone furoate (Drug)
COHORT 2 RANDOMISATION B
(5-7 years old) Repeat dose session: Matching placebo; Day 1 and Day 14 = in house dosing; Days 2-13 = home dosing
干预措施: Matching placebo (Drug)
结局指标
主要结局
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 44)
Blood samples were collected for the measurement of reticulocyte and RBCs at Day 14 of the respective treatment period.
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 6)/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 Adverse AE/SAE module for a complete list of AEs and SAEs.
Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period
时间窗: Baseline and Day 14 of the respective treatment period (up to Study Day 44)
PR, QRS, QT, QTcB, QTcF, and RR were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period. Change from Baseline was calculated as the value at Day 14 minus the Baseline value. QTcB is the QT duration corrected for heart rate by Bazett's formula. QTcF is the QT duration corrected for heart rate by Fridericia's formula.
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 44)
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.
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 44)
Blood samples were collected for the measurement of hemoglobin and MCHC at Day 14 of the respective treatment period.
Heart Rate at Baseline and Day 14 of the Respective Treatment Period
时间窗: Baseline and Day 14 of the respective treatment period (up to Study Day 44)
Heart rate (HR) was measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period.
Hematocrit Values at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 44)
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).
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 44)
Blood samples were collected for the measurement of MCV at Day 14 of the respective treatment period.
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 44)
Blood samples were collected for the measurement of albumin and total protein at Day 14 of the respective treatment period.
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 44)
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.
Total 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 44)
Blood samples were collected for the measurement of total bilirubin, creatinine, and uric acid at Day 14 of the respective treatment period.
Peak Expiratory Flow on 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 44)
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 maximum pre-dose measurement at Day 1 for each period.
Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period
时间窗: Day 14 of the respective treatment period (up to Study Day 44)
Blood samples were collected for the measurement of MCH at Day 14 of the respective treatment period.
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 44)
Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Day 14 of the respective treatment period.
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period
时间窗: Baseline and Day 14 of the respective treatment period (up to Study Day 44)
SBP and DBP were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period.
次要结局
- AUC(0-t) on Day 14 of the Respective Treatment Period(Day 14 of the respective treatment period)
- Cmax on Day 14 of the Respective Treatment Period(Day 14 of the respective treatment period)
- Tmax and t at Day 14 of the Respective Treatment Period(Day 14 of the respective treatment period)
- Serum Cortisol Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period(Day 14 of the respective treatment period)
- Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period(Days 1 and 14 of the respective treatment period)
- Distance of Assessment on Days 1 and 14 of the Respective Treatment Period(Days 1 and 14 of the respective treatment period)
- Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period(Days 1 and 14 of the respective treatment period)
- Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period)
- Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period)
- Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period)
- Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period)
- Inhalation Time on Days 1 and 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period)
- Inhaled Volume on Days 1 and 14 of the Respective Treatment Period(Day 1 and Day 14 of the respective treatment period)