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)

NCT ID: NCT01957202

Last Updated: 2017-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2014-02-28

Brief 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.

Conditions

Rhinitis, Allergic, Perennial and Seasonal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm 1

Each Subject will be assigned to a sequence of three treatments (e.g ABC, BCD, ACD): A=Two, 50 microliter (mcqL) sprays per nostril of FF, total dose 100 microgram (mcg); B=Two, 50 mcqL sprays per nostril of levocabastine, total dose 200 mcg; C=Two, 50 mcql sprays per nostril of FF/levocabastine FDC, total daily dose 100 mcg FF and 200 mcg levocabastine; D=Two, 50 mcql sprays per nostril of placebo. There will be a wash out period of 14-28 days between two treatment periods

Group Type: EXPERIMENTAL

FF/levocabastine

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

FF/levocabastine

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.

Intervention Type: DRUG

FF

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.

Intervention Type: DRUG

levocabastine

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.

Intervention Type: DRUG

Placebo

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 Type: DRUG

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.

Exclusion Criteria

• 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).

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Vienna, , Austria

Countries

Austria

References

Murdoch RD, Bareille P, Ignar D, Miller SR, Gupta A, Boardley R, Zieglmayer P, Zieglmayer R, Lemel P, Horak F. The improved efficacy of a fixed-dose combination of fluticasone furoate and levocabastine relative to the individual components in the treatment of allergic rhinitis. Clin Exp Allergy. 2015 Aug;45(8):1346-55. doi: 10.1111/cea.12556.

Reference Type: DERIVED

PMID: 25900517 (View on PubMed)

Study Documents

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

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Other Identifiers

200286

Identifier Type: -

Identifier Source: org_study_id