Clinical trial NCT01332292: Pharmacokinetics and PharmacoDynamics of GW685698 in Paedeatric Asthmatic Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: inhalation profiles
pharmacokinetics
pharyngometry
asthma
pediatric subjects
GW685698
Fluticasone furoate
safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-04-11
Enrollment: 27
Sex: ALL
Minimum age (years): 5
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
timeFrame: From the start of study medication until Week 11 (Visit 6)/Early Withdrawal
measure: Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 44)
measure: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 44)
measure: Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 44)
measure: Hematocrit Values at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 44)
measure: Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 44)
measure: Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 44)
measure: 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
timeFrame: Day 14 of the respective treatment period (up to Study Day 44)
measure: Albumin and Total Protein Values at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 44)
measure: 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
timeFrame: Day 14 of the respective treatment period (up to Study Day 44)
measure: Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 44)
measure: Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period
timeFrame: Day 1 and Day 14 of the respective treatment period (up to Study Day 44)
measure: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period
timeFrame: Baseline and Day 14 of the respective treatment period (up to Study Day 44)
measure: Heart Rate at Baseline and Day 14 of the Respective Treatment Period
timeFrame: Baseline and Day 14 of the respective treatment period (up to Study Day 44)
measure: Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period
timeFrame: Baseline and Day 14 of the respective treatment period (up to Study Day 44)
Secondary outcomes:
measure: AUC(0-t) on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period
measure: Cmax on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period
measure: Tmax and t at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period
measure: Serum Cortisol Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period
measure: Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period
timeFrame: Days 1 and 14 of the respective treatment period
measure: Distance of Assessment on Days 1 and 14 of the Respective Treatment Period
timeFrame: Days 1 and 14 of the respective treatment period
measure: Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period
timeFrame: Days 1 and 14 of the respective treatment period
measure: Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period
timeFrame: Day 1 and Day 14 of the respective treatment period
measure: Inhalation Time on Days 1 and 14 of the Respective Treatment Period
timeFrame: Day 1 and Day 14 of the respective treatment period
measure: Inhaled Volume on Days 1 and 14 of the Respective Treatment Period
timeFrame: Day 1 and Day 14 of the respective treatment period
measure: Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period
timeFrame: Day 1 and Day 14 of the respective treatment period
measure: Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period
timeFrame: Day 1 and Day 14 of the respective treatment period
measure: Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period
timeFrame: Day 1 and Day 14 of the respective treatment period
Other outcomes:
Locations:
city: Cypress
country: United States
facility: GSK Investigational Site
state: California
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Normal
country: United States
facility: GSK Investigational Site
state: Illinois
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: