E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rhinitis, Allergic, Perennial |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
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 |
The objective of this study was to assess ocular safety in adult and adolescent Perennial Allergic Rhinitis (PAR) subjects (12 years of age and older) after two years of continuous treatment with FFNS 110mcg QD. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Informed consent
•Subject has provided an appropriately signed and dated informed consent. An appropriately signed and dated assent must be obtained from the parents or guardian if the subject is a child under 18 years of age.
- Outpatient
•Subject is treatable on an outpatient basis.
- Age
•12 years of age and older at Visit 2
- Male or eligible female
Female subjects should not be enrolled if they plan to become pregnant during the time of study participation.
To be eligible for entry into the study, females of childbearing potential must commit to the consistent and correct use of an acceptable method of birth control, as defined by the following:
•Abstinence
Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of six days).
•Oral contraceptive (either combined estrogen/progestin or progestin only)
•Injectable progestogen
•Implants of levonorgestrel
•Percutaneous contraceptive patches
•Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year,
•Male partner who is sterile (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study and is the sole sexual partner for that female subject, or
•Double barrier method-condom or occlusive cap (diaphragm or cervical /vault caps) plus Spermicide,
•Estrogenic vaginal ring.
A urine pregnancy test will be done at the screening visit to confirm females of childbearing potential are not pregnant upon entry into the study. In addition, urine pregnancy tests will be done for all females of childbearing potential at each clinic visit.
- Diagnosis of PAR to include:
A positive skin test (by prick method) response to appropriate perennial allergen (house dust mites, animal dander, mold, or cockroach) within last 12 months prior to Visit 1 or at Visit 1.
A positive skin test is defined as a wheal ³3mm larger than the diluent control for prick testing.
•Two year medical history and past treatment of PAR (written or verbal confirmation) which includes perennial, i.e., year-round, symptoms. PAR symptoms could include nasal congestion, rhinorrhea, nasal itching and sneezing.
In vitro tests for specific IgE (such as RAST, PRIST) will not be allowed for the diagnosis of PAR.
NOTE: Subjects who meet the above criteria and who also may have seasonal allergic rhinitis (SAR) and/or perennial non-allergic rhinitis (PNAR) are eligible for randomization.
- Environment
•Subject must be symptomatic to appropriate perennial allergen (animal dander, house dust mites, cockroach, mold) and willing to maintain, as much as possible, the same environment throughout the study.
- Ability to comply with study procedures
Subject understands and is willing, able and likely to comply with study procedures and restrictions.
- Literate
Subject must be able to read, comprehend, and record information in English |
|
E.4 | Principal exclusion criteria |
- Significant concomitant medical conditions, defined as but not limited to:
•A historical or current evidence of clinically significant uncontrolled disease of any body system (e.g., tuberculosis, psychological disorders, eczema).
•History or current diagnosis of diabetes mellitus
•Uncontrolled hypertension (i.e., systolic blood pressure ³ 140mm Hg or diastolic blood pressure ³ 90mm Hg)
•A severe physical obstruction of the nose (e.g., deviated septum or nasal polyp) or nasal septal perforation that could affect the deposition of double blind intranasal study drug
•Nasal (e.g., nasal septum) or ocular injury/surgery in the last 6 months (including LASIK eye surgery)
•Asthma, with the exception of mild intermittent asthma
NOTE: Subjects will be allowed to use short-acting inhaled beta2 agonists ONLY on an as needed basis.
•Rhinitis medicamentosa
•Bacterial or viral infection (e.g., common cold) of the eyes or upper respiratory tract within two weeks of Visit 1 or during the screening period
•Documented evidence of acute or significant chronic sinusitis, as determined by the individual investigator
•Current or history of glaucoma and/or ocular herpes simplex
•Current cataract and/or previous history of cataract surgery
•Physical impairment that would affect subject's ability to participate safely and fully in the study
•Clinical evidence of a Candida infection of the nose
•History of psychiatric disease, intellectual deficiency, poor motivation, substance abuse (including drug and alcohol) or other conditions that will limit the validity of informed consent or that would confound the interpretation of the study results
•History of adrenal insufficiency
•History of Hepatitis B or C
- Use of corticosteroids, defined as:
•Intranasal corticosteroid within 4 weeks prior to Visit 1 (e.g., VERAMYST, FLONASE™, Nasonex, Rhinocort).
•Inhaled, oral, intramuscular, intravenous, ocular, and/or topical corticosteroids (with the exception of topical hydrocortisone, 1% or less, or equivalent) within 8 weeks prior to Visit 1.
- Use of other allergy medications within the timeframe indicated relative to Visit 1
•Intranasal or ocular cromolyn within 14 days prior to Visit 1 (e.g., Nasalcrom, Crolom)
•Short-acting prescription and non-prescription antihistamines, including ocular preparations and antihistamines contained in insomnia and "night time" pain formulations, within 3 days prior to Visit 1 (e.g., Benadryl, Chlortrimeton, Dimetane, Tavist)
•Long-acting antihistamines within 10 days prior to Visit 1 (e.g., Allegra, Claritin, Clarinex, Zyrtec).
•Intranasal antihistamines (e.g., Astelin) within 2 weeks prior to Visit 1
•Oral or intranasal decongestants within 3 days prior to Visit 1 (e.g., Sudafed)
•Long-acting beta-agonists within 3 days prior to Visit 1 (e.g., SEREVENT™, Foradil)
•Intranasal, oral, or inhaled anticholinergics within 3 days prior to Visit 1 (e.g., Atrovent)
•Oral antileukotrienes within 3 days of Visit 1 (e.g., Singulair)
•Subcutaneous omalizumab (Xolair) within 5 months of Visit 1
•Use of other medications that may affect allergic rhinitis or its symptoms
•Chronic use of concomitant medications, such as tricyclic antidepressants, that would affect assessment of the effectiveness of the study drug
•Use of other intranasally administered medications (e.g., Miacalcin)
- Use of immunosuppressive medications 8 weeks prior to screening and during the study
- Immunotherapy
Immunotherapy patients may be enrolled in the study if the immunotherapy was not initiated within 30 days of Visit 1, if the dose has remained fixed over the 30 days prior to Visit 1, and the dose will remain fixed for the duration of the study.
- Use of any medications that significantly alter the pharmacokinetics of fluticasone furoate (ritonavir and ketoconazole)
- Use of chronic treatment with agents known to promote the development of cataracts (e.g., potassium-sparing diuretics and allopurinol)
- Allergy/Intolerance
•Known hypersensitivity to corticosteroids or any excipients
- Clinical trial/experimental medication experience
•Has recent exposure to an investigational study drug within 30 days of Visit 1
•Participation in a previous or current FFNS (GW685698X) clinical study
- Positive urine pregnancy test or female who is breastfeeding
•Has a positive or inconclusive pregnancy test at Visit 1 or Visit 2
- Affiliation with investigational site
•Subject is a participating investigator, sub-investigator, study co-ordinator, or employee of a participating investigator, or is an immediate family member of the aforementioned.
- Tobacco use
•Smoking or smoker in past 6 months
- Chickenpox or measles
- Findings of a clinically significant, abnormal ECG
- Findings of a clinically significant laboratory abnormality |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Time to first occurrence of an event for LOCS III posterior subcapsular opacity (P). An event for P was
defined as an increase of 0.3 or greater from baseline in LOCS III grade for P, in either eye.
• Time to first occurrence of an event for IOP. An event for IOP was defined as an increase of 7mm Hg or
greater from baseline in IOP, in either eye, using Goldmann Applanation Tonometry. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Change from baseline in LogMAR (Logarithm of the Minimum Angle of Resolution) visual acuity using Early
Treatment Diabetic Retinopathy Study (ETDRS) charts
• Change from baseline in LOCS III parameters [nuclear opalescence (NO), nuclear color (NC), cortical
opacity (C), and P]
• Change from baseline in IOP
• Change from baseline in horizontal cup-to-disc ratio. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
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 | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
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.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |