A Proof of Concept Study to Assess Effect of Fluticasone Furoate (FF)/Levocabastine Fixed Dose Combination (FDC) Compared With Levocabastine and FF Alone in Subjects With Allergic Rhinitis (AR)
Condition: Rhinitis, Allergic, Perennial and Seasonal
MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial
Intervention: FF/levocabastine; FF; levocabastine; Placebo
Intervention description: FF/levocabastine (25mcg/50 mcg) will be supplied as intranasal aqueous microsuspension in an amber glass bottle fitted with a white top actuated plastic metering atomising spray pump filled with a uniform white suspension. Two sprays in each nostril in the morning in a fasted state will be administered.; FF (25mcg) will be supplied as intranasal aqueous microsuspension in an amber glass bottle fitted with a white top actuated plastic metering atomising spray pump filled with a uniform white suspension. Two sprays in each nostril in the morning in a fasted state will be administered.; levocabastine (50mcg) will be supplied as intranasal aqueous microsuspension in an amber glass bottle fitted with a white top actuated plastic metering atomising spray pump filled with a uniform white suspension. Two sprays in each nostril in the morning in a fasted state will be administered.; Placebo will be supplied as intranasal aqueous microsuspension in an amber glass bottle fitted with a white top actuated plastic metering atomising spray pump filled with a uniform white suspension. Two sprays in each nostril in the morning in a fasted state will be administered.
Intervention MeSH terms: Levocabastine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: levocabastine fixed dose combination, Rhinitis, Allergic, Perennial and Seasonal, Allergic Rhinitis, fluticasone furoate

Summary:

      This study will be a randomised, double blind, placebo controlled, 3-way, incomplete block
      crossover study to evaluate the effect of single and repeat doses of levocabastine, FF,
      placebo and a FDC of FF/levocabastine administration in AR subjects. The total expected study
      duration for each individual participating in the study will be a maximum of up to 20 weeks
      (including the screening and follow-up). This will be a three period study and subjects will
      be assigned to a sequence of three treatments. There will be a wash-out period of 14-28 days
      between two treatment periods. The rational for this study is to demonstrate proof of concept
      with the FDC of FF and levocabastine compared with each of the components administered alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of AR, as determined by the presence of rhinitis symptoms that last for
             several months per year, for more than 1 year and are not attributed to infections or
             nasal abnormalities.

          -  Subjects have a TNSS score of >=6 during the screening allergen challenge chamber.

          -  Subjects have a positive skin prick test (wheal >=4 millimeter [mm]) for seasonal
             pollen at or within the 12 months preceding the screening visit.

          -  Subjects have a positive radioallergosorbent test (RAST) (>=class 2) for seasonal
             pollen at or within the 12 months preceding the screening visit.

          -  There are no conditions or factors that would make the subject unlikely to be able to
             stay in the chamber for 5 hours.

          -  Male/females between 18 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 and laboratory tests. 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 agree
             and document that the finding is unlikely to introduce additional risk factors and
             will not interfere with the study procedures.

          -  Body weight >=50 kg and body mass index (BMI) within the range 19-30 kilogram per
             meter suare (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
        unit per milliliter (MIU/milliliter [mL]) and estradiol <40 picogram per milliliter[pg/mL]
        (<147 picomole per liter [pmol/L]) is confirmatory).

        Child-bearing potential with negative pregnancy test as determined by urine beta-human
        chorionic gonadotropin (β-hCG) test at screening or prior to dosing and;

          -  Agrees to use one of the contraception methods 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 1 week post-last dose

          -  Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

          -  Subjects should be non-smokers, which for this study is defined as having smoked <10
             packs per year in their lifetime, and have not smoked in the 6 months prior to the
             screening visit.

          -  alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5x upper limit
             of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35%).

          -  Based on single or averaged corrected QT interval (QTc) values of triplicate
             electrocardiogram (ECGs) obtained over a brief recording period: Fridericia's QTC
             (QTcF) <450 milliseconds (msec).

        Exclusion Criteria:

          -  Nasal abnormalities likely to affect the outcome of the study, that is nasal septal
             perforation, nasal polyps, sinusitis other nasal malformations.

          -  History of frequent nose bleeds

          -  Patients with rhinitis medicamentosa

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  Significant renal impairment, which based on the opinion of the investigator, would
             preclude the subjects participation in the study.

          -  History of regular alcohol consumption within 6 months of the study defined as:

          -  An average weekly intake of >21 units for males or >14 units for females. One unit is
             equivalent to 8 gram of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of
             wine or 1 (25 mL) measure of spirits.

          -  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.

          -  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.