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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01962467




Registration number
NCT01962467
Ethics application status
Date submitted
10/10/2013
Date registered
14/10/2013
Date last updated
15/05/2017

Titles & IDs
Public title
A Relative Bioavailability Study of Fluticasone Furoate and Levocabastine
Scientific title
A Relative Bioavailability Study to Compare the Pharmacokinetics of a Fixed Dose Combination of Fluticasone Furoate and Levocabastine With Levocabastine and Fluticasone Furoate Alone
Secondary ID [1] 0 0
200284
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rhinitis, Allergic, Perennial and Seasonal 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Allergies
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FF/LEV FDC
Treatment: Drugs - FF
Treatment: Drugs - LEV

Experimental: Arm 1 - Each subject will receive 7 once daily doses of one of the 3 treatments (FF/LEV FDC or FF or LEV) administered as two 50 µL sprays per nostril in the morning, during each of the 3 treatment periods, as per one of the 6 possible randomization sequences. Each treatment period will be separated by a minimum washout period of 14 days


Treatment: Drugs: FF/LEV FDC
Intranasal aqueous microsuspension containing 25.0 microgram (µg) of FF and 50 µg of LEV as a fixed dose combination. It will be administered as two 50 µL sprays per nostril in the morning in a fasted state

Treatment: Drugs: FF
Intranasal aqueous microsuspension containing 27.5µg of FF. It will be administered as two 50 µL sprays per nostril in the morning in a fasted state

Treatment: Drugs: LEV
Intranasal aqueous microsuspension containing 50 µg of LEV. It will be administered as two 50 µL sprays per nostril in the morning in a fasted state
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Plasma concentrations of FF and LEV
Timepoint [1] 0 0
Day 7 (Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose) and Day 8 (24 hours post-dose) of each treatment period
Primary outcome [2] 0 0
Pharmacokinetic (PK) parameters for both FF and LEV
Timepoint [2] 0 0
Day 7 (Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose) and Day 8 (24 hours post-dose) of each treatment period
Secondary outcome [1] 0 0
PK parameters for both FF and LEV alone and in combination
Timepoint [1] 0 0
Day 7 (Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose) and Day 8 (24 hours post-dose) of each treatment period
Secondary outcome [2] 0 0
tmax
Timepoint [2] 0 0
Day 7 (Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose) and Day 8 (24 hours post-dose) of each treatment period

Eligibility
Key inclusion criteria
- Male/Females aged between 18, 20 for Korean subjects, and 65 years of age inclusive,
at the time of signing the informed consent.

- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and
cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s)
which is/are not specifically listed in the inclusion or exclusion criteria, outside
the reference range for the population being studied may be included only if the
Investigator documents that the finding is unlikely to introduce additional risk
factors and will not interfere with the study procedures.

- Caucasian, defined as having four grandparents who were descendents of European
Caucasians, or Korean origin defined as being born in mainland Korea, having four
ethnic Korean grandparents, holding a Korean passport or identity papers and being
able to speak Korean. Korean subjects should also have lived outside their respective
countries for less than 10 years.

- Body weight >=50 kilogram (kg), >=45 kg for Korean subjects, and body mass index (BMI)
within the range 18 - 30 Kilogram per meter square (kg/m^2) (inclusive).

- A female subject is eligible to participate if she is of: non-childbearing potential
defined as pre-menopausal females with a documented tubal ligation or hysterectomy
[for this definition, "documented" refers to the outcome of the
investigator's/designee's review of the subject's medical history for study
eligibility, as obtained via a verbal interview with the subject or from the subject's
medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in
questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)
>40 milli-international units per milliliter (MIU/mL) and estradiol <40
picogram/milliliter (pg/mL) (<147 picomole/liter) is confirmatory]; child-bearing
potential with negative pregnancy test as determined by urine Human Chorionic
Gonadotropin (hCG) test at screening or prior to dosing AND agrees to use one of the
contraception methods as described for an appropriate period of time (as determined by
the product label or investigator) prior to the start of dosing to sufficiently
minimize the risk of pregnancy at that point. Female subjects must agree to use
contraception until 8 days post-last dose.

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form

- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5 x Upper Limit
of Normal (ULN) [isolated bilirubin >1.5 x ULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%].

- Based on single or averaged corrected QT interval (QTc) values of triplicate
electrocardiograms (ECGs) obtained over a brief recording period: QT interval
corrected for heart rate using Fridericia'sformulas (QTcF) <450 milliseconds (msec).
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Criteria Based Upon Medical Histories:

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- History of regular alcohol consumption within 6 months of the study defined as: For
Australian (AUST) sites: An average weekly intake of >21 units for males or > 14 units
for females. In Australia one unit (=standard drink) is equivalent to 10 grams (g) of
alcohol: 270 mL of full strength beer (4.8%), 375 mL of mid strength beer (3.5%), 470
mL of light beer (2.7%), 250 mL pre-mix full strength spirit (5%), 100 mL of wine
(13.5%) and 30 mL of spirit (40%).

- 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
GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.

- Nasal abnormalities likely to affect the outcome of the study, i.e., nasal septal
perforation, nasal polyps, other nasal malformations.

- History of frequent nosebleeds.

- Subjects should be non-smokers, which for this study is defined as having smoked < 10
pack years in their lifetime, and have not smoked in the 6 months prior to the
screening visit.

Criteria Based Upon Diagnostic Assessments

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- A positive pre-study drug/alcohol screen.

- A positive test for human immunodeficiency virus (HIV) antibody.

- Urine cotinine levels indicative of smoking or history or regular use of tobacco- or
nicotine-containing products within 6 months prior to screening.

- Other Criteria:

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.

- Lactating females.

- 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.

- 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.

- Any history of nasal surgery which may affect the outcome of the study (i.e.,
turbinectomy, major nasal reconstruction, septal perforation repair).

- Any history in the past 5 years of either perennial or seasonal allergic rhinitis, or
any subject expected to have symptoms of allergic rhinitis during the study.

- Subjects with recent upper respiratory tract infections (URTIs) will be allowed in the
study only if their nasal symptoms associated with the URTI have been completely
resolved for more than 3 weeks prior to screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/02/2014
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is an open label, randomized, 3-way cross-over, and repeat administration study in
healthy male and female subjects. The purpose of the study is to determine the relative
bioavailability of Fluticasone Furoate (FF) and Levocabastine (LEV), when each is
administered alone and as FF/LEV Fixed Dose Combination (FDC).This study consists of Part A
(in which 30 subjects including 12 Korean subjects will be enrolled) and Part B (in which 18
subjects will be enrolled). Each part will consist of three treatment periods separated by a
minimum washout period of 14 days. In each treatment period, subjects will receive seven
daily doses of one of the 3 treatments: FF, LEV or FF/LEV FDC, via an intranasal spray
according to one of the 6 possible randomization sequences. The study will use an adaptive
design with an interim review following Part A to confirm whether Part B is required.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01962467
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01962467