Inhaled Fluticasone Furoate/Vilanterol Safety and Tolerab... | NCT01453023

Description Module

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.

Label	Type	Description	Intervention Names
Fluticasone Furoate	Active Comparator	One of two study treatments subjects will receive. Given to allow comparison of FF exposure in combination versus as mono therapy.	Drug: Fluticasone Furoate
Fluticasone Furoate/Vilanterol	Experimental	One of two study treatments subjects will receive. FF/VI combined is being tested and compared to fluticasone furoate.	Drug: Fluticasone Furoate/Vilanterol

Name	Type	Description	Arm Group Labels	Other Names
Fluticasone Furoate	Drug	100mcg delivered via a novel dry powder inhaler on days 1-14 of one study treatment period.	Fluticasone Furoate

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	From the start of study medication until Week 11 (Visit 9)/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.	Day 14 of the respective treatment period (up to Study Day 63)
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.	Day 14 of the respective treatment period (up to Study Day 63)
Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period	Blood samples were collected for the measurement of reticulocytes and RBCs at Day 14 of the respective treatment period.	Day 14 of the respective treatment period (up to Study Day 63)

Secondary Outcomes

Measure	Description	Time Frame
AUC(0-t) and AUC(0-4) of FF on Day 14 of the Respective Treatment Period	Area under the concentration-time (AUC) curve from time zero (pre-dose) to the last time AUC(0-t) and from time zero to 4 hours AUC(0-4) of quantifiable concentration of FF on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the PK Population.

Eligibility Module

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.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Huntington Beach	California	92647	United States

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
112777	Informed Consent Form	View IPD

ID	Title	Description
FG000	FF 100 µg/VI 25 µg in TP 1 and FF 100 µg in TP 2	Participants received fluticasone furoate (FF) 100 micrograms (µg)/Vilanterol (VI) 25 µg in Treatment Period 1 and FF 100 µg in Treatment Period 2. The first 14-day treatment period was followed by a washout period of at least 7 days. Inhaled FF 100 µg/VI 25 µg and FF 100 µg were administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler.
FG001	FF 100 µg in TP 1 and FF 100 µg/VI 25 µg in TP 2	Participants received FF 100 µg in Treatment Period 1 and FF 100 µg/VI 25 µg in Treatment Period 2. The first 14-day treatment period was followed by a washout period of at least 7 days. Inhaled FF 100 µg/VI 25 µg and FF 100 µg were administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler.

ID	Title	Description
BG000	FF 100 µg/VI 25 µg and FF 100 µg in TPs 1 and 2	All participants who received FF 100 µg/VI 25 µg in Treatment Period 1 and FF 100 µg in Treatment Period 2 or FF 100 µg in Treatment Period 1 and FF 100 µg/VI 25 µg in Treatment Period 2. The first 14-day treatment period was followed by a washout period of at least 7 days. Inhaled FF 100 µg/VI 25 µg and FF 100 µg were administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

All Subjects Population: all participants who received at least one dose of study medication

Posted

Number

Participants

From the start of study medication until Week 11 (Visit 9)/Early Withdrawal

ID	Title	Description
OG000

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases