Clinical trial NCT01453296: Pharmacokinetics and Pharacodynamics of GW642444 in Paedetric Subjects
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Tolerability
Safety
Pharmacokinetics
GW642444
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-10-17
Enrollment: 28
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 paedeatric asthmatic subjects with GW642444, an orally inhaled long-acting agonist of the β2-adrenoceptor.

Detailed description: 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.

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) \>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.

Exclusion Criteria:

* 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

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 8)/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 49)
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 49)
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 49)
measure: Hematocrit Value at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 49)
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 49)
measure: Mean Corpuscle Hemoglobin (MCH) Value at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 49)
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 49)
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 49)
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 49)
measure: Total Bilirubin, Direct 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 49)
measure: Peak Expiratory Flow on Day 1, Day 8, and Day 14 of the Respective Treatment Period
timeFrame: Day 1, Day 8, and Day 14 of the respective treatment period (up to Study Day 49)
measure: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1, Day 8, and Day 14 of the Respective Treatment Period
timeFrame: Day 1, Day 8, and Day 14 of the respective treatment period (up to Study Day 49)
measure: Maximum Heart Rate at 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 49)
measure: Weighted Mean Heart Rate at 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 49)
measure: Maximum QTcF at 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 49)
measure: Weighted Mean QTcF at 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 49)
Secondary outcomes:
measure: AUC(0-t) and AUC(0-8) on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 49)
measure: Cmax on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 49)
measure: Tmax, t1/2, and t at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 49)
measure: Blood Glucose and Potassium on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 49)
measure: Average Oropharyngeal Cross-sectional Area 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 49)
measure: Distance of Assessment 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 49)
measure: Oropharyngeal Volume 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 49)
measure: Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) 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 49)
measure: Inhalation Time 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 49)
measure: Inhaled Volume 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 49)
measure: Peak Pressure Drop 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 49)
measure: Total Emitted Dose (TED) 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 49)
measure: Ex-throat Dose (ETD) and ETD <2 Microns 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 49)
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: