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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01957202
First received: October 4, 2013
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Rhinitis, Allergic, Perennial and Seasonal
Drug: FF/levocabastine
Drug: FF
Drug: levocabastine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled, 3 Way, Incomplete Block Cross Over Study in Subjects With Allergic Rhinitis to Assess the Effect of Once Daily Single and Repeat Doses of Intranasal Fluticasone Furoate/Levocabastine Fixed Dose Combination (FDC) Relative to Levocabastine and Fluticasone Furoate Alone on the Onset and Magnitude of Symptoms of Rhinitis in an Allergen Challenge Chamber

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Total Nasal Symptom Score (TNSS) after repeat FF/levocabastine compared to repeat FF alone [ Time Frame: Day 8 of each treatment period (Upto 80 days) ] [ Designated as safety issue: No ]
    TNSS will be assessed on 4 components: nasal congestion, rhinorrhea, nasal itch and sneeze, on a 4-point scale of 0-3 for maximum TNSS of 12, after 8-day repeat FF/levocabastine compared to 8-day repeat FF alone.

  • TNSS after repeat FF/levocabastine compared to repeat levocabastine alone [ Time Frame: Day 8 of each treatment period (Upto 80 days) ] [ Designated as safety issue: No ]
    TNSS will be assessed on 4 components: nasal congestion, rhinorrhea, nasal itch and sneeze, on a 4-point scale of 0-3 for maximum TNSS of 12, after 8-day repeat FF/levocabastine compared to 8-day repeat levocabastine alone.


Secondary Outcome Measures:
  • TNSS and Total Ocular Symptom Score (TOSS) after single dose of FF/levocabastine compared to FF alone [ Time Frame: Day 8 of each treatment period (Upto 80 days) ] [ Designated as safety issue: No ]
    The onset and magnitude of symptom relief on TNSS and TOSS will assessed following single dose of FF/levocabastine compared to FF alone

  • TNSS and TOSS after single dose of FF/levocabastine compared to levocabastine alone [ Time Frame: Day 8 of each treatment period (Upto 80 days) ] [ Designated as safety issue: No ]
    The onset and magnitude of symptom relief on TNSS and TOSS will assessed following single dose of FF/levocabastine compared to levocabastine alone

  • TOSS after repeat FF/levocabastine compared to repeat FF alone [ Time Frame: Day 8 of each treatment period (Upto 80 days) ] [ Designated as safety issue: No ]
    TOSS will be assessed on components: Red, Itchy, and Tearing Eyes, on a 4-point scale of 0-3 for maximum TOSS of 9, average of two eyes, after 8-day repeat FF/levocabastine compared to 8-day repeat FF alone.

  • TOSS after repeat FF/levocabastine compared to repeat levocabastine alone [ Time Frame: Day 8 of each treatment period (Upto 80 days) ] [ Designated as safety issue: No ]
    TOSS will be assessed on components: Red, Itchy, and Tearing Eyes, on a 4-point scale of 0-3 for maximum TOSS of 9, average of two eyes, after 8-day repeat FF/levocabastine compared to 8-day repeat levocabastine alone


Enrollment: 71
Study Start Date: October 2013
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: 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.
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.
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01957202

Locations
Austria
GSK Investigational Site
Vienna, Austria, A-1150
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01957202     History of Changes
Other Study ID Numbers: 200286
Study First Received: October 4, 2013
Last Updated: February 27, 2014
Health Authority: Austria: Federal Office for Safety in Health Care

Keywords provided by GlaxoSmithKline:
levocabastine fixed dose combination, Rhinitis, Allergic, Perennial and Seasonal, Allergic Rhinitis, fluticasone furoate

Additional relevant MeSH terms:
Rhinitis
Rhinitis, Allergic, Perennial
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Levocabastine
Fluticasone
Histamine H1 Antagonists, Non-Sedating
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on August 20, 2014