Study to Look at and Compare How Inhaled and Intravenous Fluticasone Furoate and GW642444 Are Processed by the Body in Healthy Subjects

An Open-label, Non-randomised, Three-way Crossover, Single Dose Study to Determine the Absolute Bioavailability of Fluticasone Furoate (FF)/GW642444 Inhalation Powder, in Healthy Subjects

This study is being done to look at the absolute bioavailability of fluticasone furoate and GW642444 inhalation powder when administered in healthy subjects. Bioavailability is determined by measuring the amount of the dose of inhaled medication that reaches the circulation; the amount of inhaled fluticasone furoate and GW642444 powder will be compared to the medication administered intravenously (where bioavailability is 100%).

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: fluticasone furoate//GW642444; Drug: fluticasone furoate; Drug: GW642444

Detailed Description

Fluticasone furoate (FF), a novel glucocorticoid, and GW642444, a potent, inhaled longacting, beta2-receptor agonist (LABA), are currently under development in combination for use as a once-daily, inhaled treatment for asthma and chronic obstructive pulmonary disease (COPD). FF is also being developed as a stand-alone product for asthma and GW642444 is also being developed as a stand-alone product and in combination with a novel, long-acting muscarinic antagonist for the treatment of COPD. This study is being performed to determine the absolute bioavailability of both FF and GW642444 when delivered in combination from the novel dry powder inhaler.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male or female between 18 and 64 years of age inclusive
• Body mass index (BMI) within the range 18.5-29 0 kg/m2 (inclusive)
• Subjects who are current non-smokers
• AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
• QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block, based on a single ECG value, or an average from three ECGs obtained over a brief recording period
• No significant abnormality on the Holter ECG at screening
• FEV1 ≥ 85% predicted at screening.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
• Subjects who are able to use the inhalation device satisfactorily

Exclusion Criteria:

• As a result of medical interview, physical examination or screening investigations, 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
• Any history of breathing problems in adult life
• Pregnant or lactating females
• The 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 a lower respiratory tract infection within 4 weeks of the screening visit
• Subjects with recent history (within 6 months) of pneumonia
• 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
• Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the new powder inhaler (i.e., lactose or magnesium stearate)
• 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
• The subject has taken oral corticosteroids less than 8 weeks before the screening visit
• The 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
• The 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
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• The subject has tested positive for HIV antibodies
• A positive pre-study urine drug screen or when randomly tested during the study
• Positive carbon monoxide (CO) or alcohol breath test at screening or on admission to the Unit.
• Positive urine cotinine test at screening
• Consumption of seville oranges, pomelos (members of the grapefruit family) or grapefruit juice from 7 days prior to the first dose of study medication
• Unwillingness or inability to follow the procedures outlined in the protocol
• Subject is mentally or legally incapacitated

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Treatment period 1; Single inhaled dose of FF (800mcg)/GW642444M (100mcg) Inhalation Powder given once daily in the morning on Day 1 of Treatment period 1	Drug: fluticasone furoate//GW642444; Single inhaled dose of FF (800mcg)/GW642444M (100mcg) Inhalation Powder administered in the morning
Other: Treatment Period 2; Single IV dose of FF (250mcg) given over 20 mins on Day 1 of Treatment period 2	Drug: fluticasone furoate; Single IV dose of FF (250mcg)
Other: Treatment Period 3; Single IV dose of GW642444M (55mcg) given over 60 mins on Day 1 of Treatment period 3	Drug: GW642444; Single IV dose of GW642444 (55mcg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute bioavailability of FF and GW642444 following single dose of FF/GW642444M Inhalation Powder; determined by measuring the amount of the dose of inhaled medication that reaches the circulation compared to the medication administered intravenously	Up to 48hr PK sampling periods profiles on 3 separate occasions over a total period of up to 5 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic parameters: AUC, Cmax, t1/2, tmax, and MRT for all treatments. In addition, volume of distribution (V) and plasma clearance (CL) for intravenous administrations and mean absorption time (MAT) for inhaled treatments	Up to 48hr PK sampling periods profiles on 3 separate occasions over a total period of up to 5 weeks
Number of Participants with clinically significant changes to Vital Signs as a measure of Safety and Tolerability	Approximately 9 weeks for each subject
Number of Participants with clinically significant changes to 12-lead ECG Tests as a measure of Safety and Tolerability	Approximately 9 weeks for each subject
Number of Participants with clinically significant changes to Clinical Laboratory Tests as a measure of Safety and Tolerability	Approximately 9 weeks for each subject
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Approximately 9 weeks for each subject

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2010
• Primary Completion (Actual): July 15, 2010
• Study Completion (Actual): July 15, 2010

Study Registration Dates

• First Submitted: June 10, 2010
• First Submitted That Met QC Criteria: February 17, 2011
• First Posted (Estimate): February 18, 2011

Study Record Updates

• Last Update Posted (Actual): June 12, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; healthy subjects; GW685698; absolute bioavailability; GW642444; fluticasone furoate
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: 102934

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: 102934
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 102934
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 102934
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 102934
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 102934
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 102934
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 102934
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register