A Study to Assess Intranasal Repeat Dose Effect of Levocabastine in the Subjects With Allergic Rhinitis
Condition: Rhinitis, Allergic, Perennial and Seasonal
MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial
Intervention: Levocabastine; Placebo
Intervention description: Intranasal aqueous 50 mcg microsuspension of levocabastine supplied in an amber glass bottle fitted with a white top actuated plastic metering atomising spray pump filled with a uniform white suspension; Intranasal aqueous 0 mcg microsuspension supplied in an amber glass bottle fitted with a white top actuated plastic metering atomising spray pump filled with a uniform white suspension
Intervention MeSH terms: Levocabastine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Allergic rhinitis; levocabastine; allergen challenge

Summary:

      This study will be a randomized, double blind, placebo controlled, 3-way cross over design in
      allergic rhinitis subjects. Subjects will receive repeat doses of intra-nasal levocabastine
      for 7 days in each period and the duration of the study will be about 13 weeks. An
      Environmental Exposure Chamber (EEC) will be used in this study. The primary objective of the
      study is to investigate the non-inferiority effect of 7 days treatment with levocabastine on
      nasal symptoms elicited by an EEC when administered once daily (QD) compared with twice daily
      (BID). Also study will be conducted to investigate the superiority of effect of 7 days
      treatment with levocabastine (QD and BID) on nasal symptoms elicited by an EEC in subjects
      compared to placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of Allergic Rhinitis (AR), as determined by the presence of seasonal or
             perennial rhinitis symptoms 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 at the baseline screening allergen challenge. Total
             nasal symptom score is the sum of nasal congestion, rhinorrhoea, nasal itch and
             sneeze, each of which are scored on a scale from 0 to 3.

          -  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 4 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, 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 agree and document that the finding is unlikely to introduce additional
             risk factors and will not interfere with the study procedures.

          -  Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 19 - 30 kg
             per meter square (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 (MlU/mL) and estradiol <40 picogram
             (pg)/mL (<147 picomol per liter [pmol/L]) 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 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 (ALP) and bilirubin <=1.5 x 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 QTc (QTcF)
             <450 milliseconds (msec).

        Exclusion Criteria:

          -  Nasal abnormalities likely to affect the outcome of the study, i.e. nasal septal
             perforation, nasal polyps, sinusitis and other nasal malformations.

          -  History of frequent nosebleeds.

          -  Subjects 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 subject's participation in the study.

          -  History of regular alcohol consumption within 6 months of the study defined as: an
             average weekly intake of >14 drinks for males or >7 drinks for females. One drink is
             equivalent to 12 g of alcohol: 12 ounces (360mL) of beer, 5 ounces (150mL) of wine or
             1.5 ounces (45ml) of 80 proof distilled 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.

          -  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.

          -  Chronic oral steroids discontinued less than 6 months prior to screening.

          -  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.

        Subjects who are using some of the medications below on an as needed basis, may participate
        in the study if they remain free of medication for the following periods of time prior to
        screening and prior to dosing (study drugs): Nasal antihistamines: 72 hours, Oral
        antihistamines A (cetirizine, fexofenadine, loratadine, desloratadine): 72 hours, Oral
        antihistamines B (all others): 72hours, Eye and Nasal Levocasbastine: 7 days, Nasal
        decongestants: 24 hours, Oral decongestants: 24 hours, Nasal glucocorticosteroids: 7 days,
        Inhaled glucocorticoids: 1 week, Oral glucocorticosteroids: 12 weeks, Oral leukotriene
        receptor antagonists: 7 days, Oral 5-lipoxygenase inhibitors: 7 days, Oral methylxanthines:
        7 days

          -  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.