Clinical trial NCT01453023: Inhaled Fluticasone Furoate/Vilanterol Safety and Tolerability, PK and PD Study
Official title: A Randomized, Double-blind, Repeat Dose, Two Period Crossover Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of Inhaled Fluticasone Furoate/Vilanterol 100/25 Micrograms in Children Aged 5 to 11 Years With Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: pediatric ages 5 to 11 years
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-10-17
Enrollment: 26
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 safety and tolerability, pharmacokinetics, and pharmacodynamics of fluticasone furoate/vilanterol (FF/VI) 100/25mcg administered using the novel dry powder inhaler in children aged 5 to 11 years with persistent asthma.

Detailed description: This study will investigate the safety and tolerability, pharmacokinetics, and pharmacodynamics of fluticasone furoate/vilanterol (FF/VI) 100/25mcg administered using the novel dry powder inhaler in children aged 5 to 11 years with persistent asthma. Fluticasone furoate (FF, GW685698) is a novel once daily inhaled corticosteroid (ICS) and vilanterol (VI, GW642444) is an inhaled once daily long-acting beta2 agonist (LABA). FF/VI is a novel ICS/LABA combination with once-daily dosing being developed for the treatment of asthma in adults, adolescents, and children of 5 years and above.

This study will be a randomized, double-blind, repeat dose, two period crossover study, with FF as the control. During each of two treatment periods subjects will receive either FF/VI 100/25 micrograms (mcg) or FF 100 mcg daily on 14 consecutive mornings via the novel dry powder inhaler. Approximately 26 subjects will be recruited into this study, with a target of 20 completed subjects. Safety, tolerability, pharmacokinetics and glucose , potassium and cortisol levels will be investigated.

Eligibility criteria: Inclusion Criteria:

* Healthy as determined by a study physician, based medical history, physical examination, laboratory testing, and electrocardiogram (ECG); with no significant medical condition apart from asthma, eczema, or rhinitis. A subject with a clinical abnormality or laboratory parameters outside the reference range for this study may be included if the Investigator and GSK Medical Monitor agree the finding is unlikely to introduce additional risk factors or interfere with the study procedures.
* Male and pre-menarchial female subjects aged 5 to less than 12 years on the last planned treatment day are eligible for this study. Pre-menarchial females are defined as any female who has not begun menses and is considered Tanner Stage 2 or less.
* Diagnosis of asthma at least 6 months prior to screening.
* Stable asthma therapy (fluticasone propionate, total daily dose less than or equal to 400 microgram or equivalent) and short acting beta-agonist (SABA) inhaler for at least 4 weeks prior to screening.
* Subjects must be controlled on their existing asthma treatment at screening, which will be continued during the run-in, washout and run-out periods (but not during active treatment periods). Control is defined as a Childhood Asthma Control Test score of \>19 and (Peak Expiratory Flow) PEF more than 75 percent predicted.
* Subjects must demonstrate an ability to accept and effectively use a demonstration inhaler from the demonstration kits provided.
* Subjects must weigh at least 20 kilograms.
* The subject and parent/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 have the ability to manage study drug administration and PEF assessments.
* At least one parent/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 for children aged 7 to 11 years.

Exclusion Criteria:

* Subjects with a history of life-threatening asthma, an asthma exacerbation requiring systemic corticosteroids or Emergency Room attendance (within 3 months) or requiring hospitalization (within 6 months) prior to screening.
* Subjects with any medical condition or circumstance making the volunteer unsuitable for participation in the study.
* Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear, not resolved within 4 weeks of screening leading to a change in asthma management; or, in the opinion of the investigator, is likely to affect the subject's asthma status or ability to participate in the study.
* Clinical visual evidence of oral candidiasis at screening.
* Subjects currently receiving (or have received within 4 weeks of screening) asthma therapies including theophyllines, long-acting inhaled beta-agonists, oral beta-agonists, or who have changed their asthma medication within 4 weeks of screening.
* Significant abnormality of rate, interval, conduction or rhythm in the 12-lead ECG (electrocardiogram), determined by the investigator in conjunction with the age and gender of the child and the assessment provided by the remote analysis service.
* QTcF (QT interval corrected for heart rate using Fridericia's formula) more than 450 milliseconds or an ECG not suitable for QT measurement (e.g. poorly defined termination of the T wave).
* Aspartarte aminotransferase, Alanine aminotransferase, alkaline phosphatase and bilirubin more than 1.5 times Upper Limit of Normal (ULN) (isolated bilirubin more than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent).
* A known or suspected sensitivity to any constituents of the novel dry powder inhaler (i.e. lactose or magnesium stearate) (e.g. history of severe milk protein allergy)
* Any adverse reaction including immediate or delayed hypersensitivity to any beta-2-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic corticosteroid therapy.
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
* Consumption of red wine, seville oranges, grapefruit or grapefruit juice, and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
* The subject has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* Where participation in the study would result in donation of blood or blood products in excess of the lesser of 50 millilitres (mL) or 3mL per kilogram within a 56 day period.
* Parent/guardian has a 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.
* Unwillingness or inability of the subject or parent/guardian to follow the procedures outlined in the protocol.
* Subject who is mentally or legally incapacitated.
* Children who are wards of the state or government.
* 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.

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 9)/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 63)
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 63)
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 63)
measure: Hematocrit Values at Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
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 63)
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 63)
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 63)
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 63)
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 63)
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 63)
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 63)
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) 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 63)
measure: Change From Baseline in Heart Rate at Day1 and Day 14 of the Respective Treatment Period
timeFrame: Day 1 and Day 14 of the respective treatment period (up to Study Day 63)
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 63)
Secondary outcomes:
measure: AUC(0-t) and AUC(0-4) of FF on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
measure: Cmax of FF on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
measure: Tmax and Tlast of FF on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
measure: AUC(0-t) and AUC(0-4) of VI on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
measure: Cmax of VI on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
measure: Tmax and Tlast of VI on Day 1 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
measure: Blood Glucose and Potassium Values on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
measure: Serum Cortisol (SC) Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
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 X)
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 63)
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 63)
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 63)
measure: Inhalation Time on Days 1 and 14 of of the Respective Treatment Period
timeFrame: Day 1 and Day 14 of the respective treatment period (up to Study Day 63)
measure: Inhaled Volume on Days 1 and 14 of the Respective Treatment Period
timeFrame: Day 1 and Day 14 of the respective treatment period (up to Study Day 63)
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 (up to Study Day 63)
measure: Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
measure: Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period
timeFrame: Day 14 of the respective treatment period (up to Study Day 63)
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: