Last updated: 11/07/2018 06:12:56
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
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: An open-label, randomised, two-way crossover study, to evaluate and compare the pharmacokinetics of fluticasone furoate, administered from a novel dry powder device (repeat dose) and intravenously (single dose), in healthy Caucasian, Japanese, Korean and Chinese subjects
Trial description: 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.
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
FF Pharmacokinetic parameters: AUC, Cmax, t1/2, tmax for inhaled and intravenous treatments. Volume of distribution (V) and plasma clearance (CL) for intravenous FF
Timeframe: up to 72hr PK sampling periods profiles on 4 separate occasions over a total period of approximately 4-5 weeks
Secondary outcomes:
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
Timeframe: 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)
Timeframe: 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
Timeframe: 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.
Timeframe: 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
Timeframe: Throughout study from screening to end of treatment periods; approximately 8 weeks
Interventions:
Enrollment:
80
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Allen A, Bal J, Cheesbrough A, Hamilton M, Kempsford R.Pharmacokinetics and pharmacodynamics of intravenous and inhaled fluticasone furoate in healthy Caucasian and East Asian subjects.Br J Clin Pharmacol.2014;77(5):808-20
Medical condition
Asthma
Product
fluticasone furoate
Collaborators
Not applicable
Study date(s)
September 2009 to December 2009
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
20 - 64 years
Accepts healthy volunteers
No
- Healthy male or female between 20 and 64 years of age inclusive
- Caucasian, Japanese, Korean or Chinese
- 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
Inclusion and exclusion criteria
Inclusion criteria:
- 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 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
Exclusion criteria:
- 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.
- Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- Positive for HIV antibodies.
- Positive pre-study urine drug screen or when randomly tested during the study.
- Positive carbon monoxide 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.
Trial location(s)
Location
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2009-23-12
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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