| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Allergic rhinitis (AR) in its seasonal and perennial form is a common allergic condition. It is clinically defined as a symptomatic disorder induced by immunoglobulin E (IgE)-
mediated inflammation after allergen exposure to mucous membranes of the nose. |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Effect of 8 day treatment with intranasal FF/levocabastine on nasal symptoms elicited by an allergen chamber challenge in subjects with allergic rhinitis when
administered once daily compared with FF and levocabastine alone. |
|
| E.2.2 | Secondary objectives of the trial |
-To determine the time to onset of symptom relief following the first dose of FF/levocabastine relative to FF alone on
nasal symptoms elicited by an allergen chamber challenge in subjects with allergic rhinitis.
-Effect of 8 day treatment with intranasal FF/levocabastine on occular symptoms elicited by an allergen chamber challenge in subjects with allergic rhinitis when administered once daily compared with FF and levocabastine alone. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.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.
2.Subjects have a TNSS score of ≥6 during the screening allergen challenge chamber.
3.Subjects have a positive skin prick test (wheal ≥ 4mm) for seasonal pollen at or within the 12 months preceding the screening visit.
4.Subjects have a positive RAST (≥ class 2) for seasonal pollen at or within the 12 months preceding the screening visit.
5.There are no conditions or factors that would make the subject unlikely to be able to stay in the chamber for 5 hours.
6.Male/females between 18 and 65 years of age inclusive, at the time of signing the informed consent.
7.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.
8.Body weight ≥50 kg and BMI within the range 19 – 30 kg/m2 (inclusive).
9.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 MIU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory].
-Child-bearing potential with negative pregnancy test as determined by urine βhCG test at screening or prior to dosing AND
10.Agrees to use one of the contraception methods listed in Section 4.3.1 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
11.Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
12.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.
13.ALT, alkaline phosphatase and bilirubin <or=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
14.Based on single or averaged QTc values of triplicate ECGs obtained over a brief recording period:
a.QTcF < 450 msec;
|
|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Criteria Based Upon Medical Histories
1.Nasal abnormalities likely to affect the outcome of the study, i.e. nasal septal perforation, nasal polyps, sinusitis other nasal malformations.
2.History of frequent nosebleeds
3.Patients with rhinitis medicamentosa
4.Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
5.Significant renal impairment, which based on the opinion of the investigator, would preclude the subjects participation in the study.
6.History of regular alcohol consumption within 6 months of the study defined as:
7.An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
8.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.
Criteria Based Upon Diagnostic Assessments
1.A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
2.A positive pre-study drug/alcohol screen.
3.A positive test for HIV antibody.
Other Criteria
1.Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
2.Lactating females.
3.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).
4.Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
5.Chronic oral steroids discontinued less than 6 months prior to screening.
6.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 Levocabastine: 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.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
TNSS on Day 8, after 8-day repeat
FF/levocabastine compared to 8-day repeat FF alone.
TNSS on Day 8 after 8-day repeat FF/levocabastine compared to 8-day repeat levocabastine alone. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| TNSS and TOSS Day 8 time points = 1h post dose (start of the challenge) and then every 15 mins until 5h post dose |
|
| E.5.2 | Secondary end point(s) |
-The onset and magnitude of symptom relief on TNSS and TOSS following a single dose of FF/levocabastine compared to FF alone.
-The onset and magnitude of symptom relief on TNSS and TOSS following a single dose of FF/levocabastine compared to levocabastine alone.
-TOSS (Total Ocular Symptom Score) on Day 8 after 8-day repeat FF/levocabastine compared to 8-day repeat FF alone.
-TOSS on Day 8 after 8-day repeat FF/levocabastine compared to 8-day repeat levocabastine alone. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| TNSS and TOSS Day 8 time points = 1h post dose (start of the challenge) and then every 15 mins until 5h post dose |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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