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)

NCT01957202 | Completed Phase 2 Results

• 1 other identifier: 200286
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

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

Keywords

levocabastine fixed dose combination, Rhinitis, Allergic, Perennial and Seasonal, Allergic Rhinitis, fluticasone furoate

Outcome Measures

Primary Outcomes (1)

• Weighted Mean of the Total Nasal Symptom Score (TNSS) (0-4) Hours (h) Post Start of Allergen Chamber Challenge on Day 8 of Each Treatment Period

  The TNSS (score of 0-12) is defined as the sum of the symptom scores for the four individual components (nasal congestion, rhinorrhea, nasal itch, and sneezing, each scored on 0-3 scale \[0=none, 1=mild, 2=moderate, 3=severe\]). TNSS was measured at the pre-allergen chamber challenge, and then every 15 minutes from 0 to 4 hours post start of the allergen chamber challenge. In the Environmental Exposure Chamber (EEC), aerosolized allergen was administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. Weighted mean TNSS was calculated by dividing the value of the area under the response time curve over the 0-4 hours (calculated by trapezoidal rule) by the time interval of available data.

  Day 8 of each treatment period (up to 80 days)

Secondary Outcomes (3)

• Weighted Mean of the Magnitude of Symptom Relief on Total Nasal Symptom Score (TNSS) (2-4) Hours (h) Post Start of Allergen Chamber Challenge on Day 1 of Each Treatment Period

  Day 1 of each treatment period (up to 80 days)

• Weighted Mean of the Magnitude of Symptom Relief on Total Ocular Symptom Score (TOSS) (2-4) Hours (h) Post Start of Allergen Chamber Challenge on Day 1 of Each Treatment Period

  Day 1 of each treatment period (up to 80 days)

• Weighted Mean of the Total Ocular Symptom Score (TOSS) (0-4) Hours (h) Post Start of Allergen Chamber Challenge on Day 8 of Each Treatment Period

  Day 8 of each treatment period (up to 80 days)

Study Arms (1)

Arm 1

EXPERIMENTAL

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

Drug: FF/levocabastine; Drug: FF; Drug: levocabastine; Drug: Placebo

Interventions

FF/levocabastine 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.

Arm 1

FF 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.

Arm 1

levocabastine 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.

Arm 1

Placebo 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.

Arm 1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Vienna, A-1150, Austria

Location

Related Publications (1)

• 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.

  PMID: 25900517 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Rhinitis; Rhinitis, Allergic

Interventions

levocabastine

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2013
• First Posted: October 8, 2013
• Study Start: October 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: January 9, 2017
• Results First Posted: October 8, 2014

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)