Rhinitis, Allergic, Perennial and Seasonal
Conditions
Keywords
Allergic rhinitis, healthy volunteers, fluticasone furoate, levocabastine, fixed dose combination, pharmacokinetics
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.
Interventions
DRUGFF/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
DRUGFF
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
DRUGLEV
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
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentrations of FF and LEV | 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 | Concentrations of FF and LEV will be determined in plasma samples |
| Pharmacokinetic (PK) parameters for both FF and LEV | 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 | From the plasma concentration-time data, area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) of FF and LEV were determined |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters for both FF and LEV alone and in combination | 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 | From the plasma concentration-time data, AUC, Cmax and time to maximum observed plasma drug concentration (tmax) of FF and LEV alone and in combination were determined for healthy Korean male and female subjects |
| tmax | 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 | Tmax of FF and LEV alone and in combination were determined for healthy male and female subjects |
Countries
Australia
Outcome results
None listed