Inhaled Fluticasone Furoate/Vilanterol Safety and Tolerability, PK and PD Study

NCT01453023 | Completed Phase 2 Results

• 1 other identifier: 112777
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

pediatric ages 5 to 11 years

Outcome Measures

Primary Outcomes (15)

• 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)

• Hematocrit Values at Day 14 of the Respective Treatment Period

  Blood samples were collected for the measurement of hematocrit at Day 14 of the respective treatment period. Hematocrit is a measure of the percentage of the volume of the whole blood that is composed of red blood cells, as determined by separation of red blood cells from the plasma (usually by centrifugation).

  Day 14 of the respective treatment period (up to Study Day 63)

• Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period

  Blood samples were collected for the measurement of MCV at Day 14 of the respective treatment period.

  Day 14 of the respective treatment period (up to Study Day 63)

• Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period

  Blood samples were collected for the measurement of MCH at Day 14 of the respective treatment period.

  Day 14 of the respective treatment period (up to Study Day 63)

• 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

  Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Day 14 of the respective treatment period.

  Day 14 of the respective treatment period (up to Study Day 63)

• Albumin and Total Protein Values at Day 14 of the Respective Treatment Period

  Blood samples were collected for the measurement of albumin and total protein at Day 14 of the respective treatment period.

  Day 14 of the respective treatment period (up to Study Day 63)

• 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

  Blood samples were collected for the measurement of calcium, chloride, carbon dioxide content/bicarbonate (CO2/BI), glucose, potassium, sodium, and urea/BUN at Day 14 of the respective treatment period.

  Day 14 of the respective treatment period (up to Study Day 63)

• Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period

  Blood samples were collected for the measurement of total bilirubin, direct bilirubin, creatinine, and uric acid at Day 14 of the respective treatment period.

  Day 14 of the respective treatment period (up to Study Day 63)

• Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period

  Peak Expiratory Flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF is calculated as the maximum of three readings taken at each timepoint for each participant. Baseline is defined as the maximum pre-dose measurement at Day 1 for each period.

  Day 1 and Day 14 of the respective treatment period (up to Study Day 63)

• Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period

  SBP and DBP were measured at Day 1 and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1. Change from Baseline was calculated as the Day 14 value minus the Baseline value.

  Day 1 and Day 14 of the respective treatment period (up to Study Day 63)

• Change From Baseline in Heart Rate at Day1 and Day 14 of the Respective Treatment Period

  Heart rate (HR) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Baseline is defined as the pre-dose measurement at Day 1. Change from Baseline was calculated as the Day 14 value minus the Baseline value. Treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect.

  Day 1 and Day 14 of the respective treatment period (up to Study Day 63)

• Maximum QTcF at Day 1 and Day 14 of the Respective Treatment Period

  QTcF is the QT domain corrected for heart rate by Fridericia's formula. Treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect.

  Day 1 and Day 14 of the respective treatment period (up to Study Day 63)

Secondary Outcomes (17)

• AUC(0-t) and AUC(0-4) of FF on Day 14 of the Respective Treatment Period

  Day 14 of the respective treatment period (up to Study Day 63)

• Cmax of FF on Day 14 of the Respective Treatment Period

  Day 14 of the respective treatment period (up to Study Day 63)

• Tmax and Tlast of FF on Day 14 of the Respective Treatment Period

  Day 14 of the respective treatment period (up to Study Day 63)

• AUC(0-t) and AUC(0-4) of VI on Day 14 of the Respective Treatment Period

  Day 14 of the respective treatment period (up to Study Day 63)

• Cmax of VI on Day 14 of the Respective Treatment Period

  Day 14 of the respective treatment period (up to Study Day 63)

Study Arms (2)

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

Interventions

Fluticasone Furoate DRUG

100mcg delivered via a novel dry powder inhaler on days 1-14 of one study treatment period.

Also known as: FF

Fluticasone Furoate

Fluticasone Furoate/Vilanterol DRUG

100/25 mcg delivered via a novel dry powder inhaler on days 1-14 of one study treatment period.

Also known as: FF/VI

Fluticasone Furoate/Vilanterol

Eligibility Criteria

• Age: 5 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Huntington Beach, California, 92647, United States

Location

Related Links

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

MeSH Terms

Conditions

Asthma

Interventions

fluticasone furoate; vilanterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2011
• First Posted: October 17, 2011
• Study Start: October 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: January 11, 2017
• Results First Posted: August 9, 2013

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)