A Relative Bioavailability Study of Fluticasone Furoate and Levocabastine
Trial end date:
SummaryThis 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.
Accepts Healthy Volunteers?Accepts Healthy Volunteers
- 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).
- 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
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
- 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
- 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