Study to Look at and Compare How Inhaled and Intravenous Fluticasone Furoate is Processed by the Body in Healthy Caucasian, Japanese, Korean and Chinese Subjects

NCT01000597 | Completed Phase 1

• 1 other identifier: 113477
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Previous studies have shown potentially higher exposure to fluticasone furoate in Japanese subjects compared with Caucasian subjects. The reasons for these potential differences are unclear. Therefore this study is being done to look at and compare how fluticasone furoate is processed by the body in healthy Caucasian, Japanese, Korean and Chinese subjects after inhaled and intravenous administration. The data obtained will be used to help in the clinical development of the drug in Japanese and other East Asian populations.

Conditions

Asthma

Keywords

pharmacokinetics; serum cortisol; pharmacodynamics; fluticasone furoate; healthy Caucasian, Japanese, Korean and Chinese subjects

Outcome Measures

Primary Outcomes (1)

• FF Pharmacokinetic parameters: AUC, Cmax, t1/2, tmax for inhaled and intravenous treatments. Volume of distribution (V) and plasma clearance (CL) for intravenous FF

  up to 72hr PK sampling periods profiles on 4 separate occasions over a total period of approximately 4-5 weeks

Secondary Outcomes (5)

• Pharmacokinetic parameters MRT for both inhaled and intravenous treatments; MAT, AUC(0-t) for 200mcg dose,observed accumulation (Ro) and absolute bioavailability for inhaled treatment

  up to 72hr PK sampling periods profiles on 4 separate occasions over a total period of approximately 4-5 weeks

• Pharmacodynamics; serum cortisol for 200mcg inhaled FF treatment only: 24 hour weighted mean (on Day -1 and Day 7)

  Two 24 hour sampling periods approximately 1 week apart

• • Ratio of twenty-four hour urine cortisol to 6-beta-hydroxy-cortisol (on Day -1 of first treatment period only). Plasma 4-beta-hydroxy-cholesterol (single sample, on Day -1 of first treatment period only). Measure of baseline CYP3A4 activity

  One collection period of up to 24 hours

• • Vital signs, 12-lead ECG, Clinical laboratory tests, forced expiratory volume in 1 second (FEV1) (at screening), peak expiratory flow rate (PEFR), AEs.

  Throughout study; approx 10 weeks

• Quantity of the total emitted dose (TED), ex-throat dose (ETD) and mass less than 2 micrometer of inhaled FF for each subject, assessed by pharyngometry, inhalation profile, breath hold and lung volume measurements

  Throughout study from screening to end of treatment periods; approximately 8 weeks

Study Arms (2)

Treatment Y

OTHER

Seven inhaled doses of 200mcg FF given once daily in the morning (Part A; Days 1-7) followed by seven inhaled doses of 800mcg FF given once daily in the morning (Part B; Day 1 and Days 3-8, i.e. no dose on Day 2).

Drug: fluticasone furoate

Treatment Z

OTHER

A single intravenous dose of 250mcg FF given over 20 minutes (Day 1).

Drug: fluticasone furoate

Interventions

fluticasone furoate DRUG

Seven inhaled doses of 200mcg FF given once daily in the morning (Part A; Days 1-7) followed by seven inhaled doses of 800mcg FF given once daily in the morning (Part B; Day 1 and Days 3-8, i.e. no dose on Day 2). A single intravenous dose of 250mcg FF given over 20 minutes (Day 1).

Treatment Y; Treatment Z

Eligibility Criteria

• Age: 20 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female between 20 and 64 years of age inclusive
• Caucasian, Japanese, Korean or Chinese
• Body mass index (BMI) for Caucasians within the range 18.5-29.0 kg/m2 (inclusive). For East Asians BMI within the range 18.5-24.9 kg/m2 (inclusive) and height 1.55m-1.85m (inclusive)
• Non-smokers
• AST, ALT, alkaline phosphatase and bilirubin \</=1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
• No significant abnormality on 12-lead ECG at screening
• No significant abnormality on the Holter ECG at screening
• FEV1 \>/= 85% predicted at screening
• Capable of giving written informed consent
• Subjects who are able to use the inhalation device satisfactorily

You may not qualify if:

• As a result of screening medical exam, the principal investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 145 mmHg or a diastolic pressure above 85 mmHg unless the Investigator confirms that it is satisfactory for their age.
• Any history of breathing problems in adult life
• Pregnant or lactating females
• Subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Subjects who have suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• History of milk protein allergy.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) 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.
• Subject has taken oral corticosteroids less than 8 weeks before the screening visit.
• Subject has taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit.
• History of alcohol/drug abuse or dependence within 12 months of the study
• Subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 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 500 mL within a 56 day period.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

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.
• Results for study 113477 can be found on the GSK Clinical Study Register.

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

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2009
• First Posted: October 23, 2009
• Study Start: September 17, 2009
• Primary Completion: December 23, 2009
• Study Completion: December 23, 2009
• Last Updated: June 22, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)