Pharmacokinetics and PharmacoDynamics of GW685698 in Paedeatric Asthmatic Patients

NCT01332292 | Completed Phase 2 Results

• 1 other identifier: 102942
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 5

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.

Conditions

Asthma

Keywords

inhalation profiles; pharmacokinetics; pharyngometry; asthma; pediatric subjects; GW685698; Fluticasone furoate; safety

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 6)/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 44)

• 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 44)

• Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period

  Blood samples were collected for the measurement of reticulocyte and RBCs at Day 14 of the respective treatment period.

  Day 14 of the respective treatment period (up to Study Day 44)

• 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 44)

• 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 44)

• 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 44)

• 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 44)

• 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 44)

• 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 44)

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

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

  Day 14 of the respective treatment period (up to Study Day 44)

• 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 44)

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

  SBP and DBP were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period.

  Baseline and Day 14 of the respective treatment period (up to Study Day 44)

• Heart Rate at Baseline and Day 14 of the Respective Treatment Period

  Heart rate (HR) was measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period.

  Baseline and Day 14 of the respective treatment period (up to Study Day 44)

• Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period

  PR, QRS, QT, QTcB, QTcF, and RR were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period. Change from Baseline was calculated as the value at Day 14 minus the Baseline value. QTcB is the QT duration corrected for heart rate by Bazett's formula. QTcF is the QT duration corrected for heart rate by Fridericia's formula.

  Baseline and Day 14 of the respective treatment period (up to Study Day 44)

Secondary Outcomes (13)

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

  Day 14 of the respective treatment period

• Cmax on Day 14 of the Respective Treatment Period

  Day 14 of the respective treatment period

• Tmax and t at Day 14 of the Respective Treatment Period

  Day 14 of the respective treatment period

• Serum Cortisol Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period

  Day 14 of the respective treatment period

• Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period

  Days 1 and 14 of the respective treatment period

Study Arms (4)

COHORT 1 RANDOMISATION A

ACTIVE COMPARATOR

(8-11 years old) Repeat dose session: Fluticasone furoate 100µg; Day 1 and Day 14 = in house dosing; Day 2-13 = home dosing

Drug: Fluticasone furoate

COHORT 1 RANDOMISATION B

PLACEBO COMPARATOR

(8-11 years old) Repeat dose session: matching placebo; Day 1 and Day 14 = in house dosing; Days 2-13 = home dosing

Drug: Matching placebo

COHORT 2 RANDOMISATION A

ACTIVE COMPARATOR

(5-7 years old) Repeat dose session: Fluticasone furoate 100µg; Day 1 and Day 14 = in house dosing; Days 2-13 = home dosing

Drug: Fluticasone furoate

COHORT 2 RANDOMISATION B

PLACEBO COMPARATOR

(5-7 years old) Repeat dose session: Matching placebo; Day 1 and Day 14 = in house dosing; Days 2-13 = home dosing

Drug: Matching placebo

Interventions

Fluticasone furoate DRUG

Novel dry powder inhaler: 100µg per blister One blister strip containing fluticasone furoate micronised drug blended with lactose and a second blister strip containing lactose and magnesium stearate.

COHORT 1 RANDOMISATION A; COHORT 2 RANDOMISATION A

Matching placebo DRUG

Novel dry powder inhaler: One blister strip containing lactose and a second blister strip containing lactose and magnesium stearate.

COHORT 1 RANDOMISATION B; COHORT 2 RANDOMISATION B

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (5)

GSK Investigational Site

Cypress, California, 90630, United States

Location

GSK Investigational Site

Huntington Beach, California, 92647, United States

Location

GSK Investigational Site

Denver, Colorado, 80206, United States

Location

GSK Investigational Site

Normal, Illinois, 61761, United States

Location

GSK Investigational Site

Medford, Oregon, 97504, 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

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 28, 2010
• First Posted: April 11, 2011
• Study Start: May 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: March 23, 2017
• Results First Posted: September 16, 2013

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will share

Locations

US (5)