Pharmacokinetics and PharmacoDynamics of GW685698 in Paedeatric Asthmatic Patients

GlaxoSmithKline27 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Asthma

Interventions

Fluticasone furoateDRUG

Novel dry powder inhaler: 100µg per blister One blister strip containing fluticasone furoate micronised drug blended with lactose and a second blister strip containing lactose and magnesium stearate.

Matching placeboDRUG

Novel dry powder inhaler: One blister strip containing lactose and a second blister strip containing lactose and magnesium stearate.

Eligibility

Sex: ALLMin age: 5 YearsMax age: 11 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Locations (5)

GSK Investigational Site

Cypress, California, United States

GSK Investigational Site

Huntington Beach, California, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Normal, Illinois, United States

Outcomes

Primary Outcomes

Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period

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.

Time frame: From the start of study medication until Week 11 (Visit 6)/Early Withdrawal

Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period

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.

Time frame: Day 14 of the respective treatment period (up to Study Day 44)

Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period

Blood samples were collected for the measurement of hemoglobin and MCHC at Day 14 of the respective treatment period.

Time frame: Day 14 of the respective treatment period (up to Study Day 44)

Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period

Blood samples were collected for the measurement of reticulocyte and RBCs at Day 14 of the respective treatment period.

Time frame: Day 14 of the respective treatment period (up to Study Day 44)

Hematocrit Values at Day 14 of the Respective Treatment Period

Data from ClinicalTrials.gov

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Secondary Outcomes

AUC(0-t) on Day 14 of the Respective Treatment Period

Area under the concentration-time (AUC(0-t)) curve from time zero (pre-dose) to the last time of quantifiable concentration of FF on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period. Due to non-quantifiable values, it was not possible to derive AUC(0-12).

Time frame: Day 14 of the respective treatment period

Cmax on Day 14 of the Respective Treatment Period

Cmax is defined as the maximum observed concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.

Time frame: Day 14 of the respective treatment period

Tmax and t at Day 14 of the Respective Treatment Period

tmax is defined as the time to reach the observed maximum concentration, and t is defined as the time of the last observed quantifiable concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.

Time frame: Day 14 of the respective treatment period

Serum Cortisol Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period

Serum cortisol weighted mean was determined for each participant over the time period 0-12 hours on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.

Time frame: Day 14 of the respective treatment period

Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period

During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.

Time frame: Days 1 and 14 of the respective treatment period

Distance of Assessment on Days 1 and 14 of the Respective Treatment Period

During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Distance of assessment is defined as the distance (length measured in centimeters \[cm\]) estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of each treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.

Time frame: Days 1 and 14 of the respective treatment period

Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period

During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Oropharyngeal volume is defined as the volume (cm\^3) of the mouth and throat estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.

Time frame: Days 1 and 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

During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Average flow rate is defined as the average inspiratory flow rate (Liters \[L\]/min) across the inhalation profile when inhaling across the resistance of the inhaler. PIFR is defined as the Peak Inspiratory Flow Rate (L/min) of the inhalation profile when inhaling across the resistance of the inhaler.The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the average flow rate and PIFR were determined.