| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Perennial allergic rhinitis |
|
| 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 primary objective of this study is to assess the safety and tolerability of 12 months treatment with intranasal GW685698X 100mcg once daily (QD) in subjects >=12 years of age with PAR. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Subject has provided an appropriately signed and dated informed consent and one has been obtained from the subject’s parent or guardian if the child is under 18 years of age.
2. Subjects must be >=12 years of age at Visit 1, either gender, any ethnic group.
3. Subject is treatable on an outpatient basis.
4. Gender: Male or female
To be eligible for entry into the study, females of child-bearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined by the following:
- Male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female subject
- Implants of levonorgestrel
- Injectable progestogen
- Oral contraceptive (either combined or progestin only)
- Double barrier method – spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm).
- Any intrauterine device (IUD) with a documented failure rate of less than 1% per year, or
- Females of childbearing potential who are not sexually active and are not on one of the above acceptable methods of contraception 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).
Female subjects should not be enrolled if they plan to become pregnant during the time of study participation.
A urine pregnancy test will be done at the screening visit to confirm female subjects are not pregnant upon entry into the study. Urine pregnancy tests will be done for all female subjects at each monthly visit.
5. Diagnosis of PAR as follows:
- A positive skin test (by prick method) response to appropriate perennial allergen (animal dander, house dust mites, cockroach, mould) within last 12 months prior to Visit 1.
A positive skin test is defined as a wheal >=3mm 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 would include nasal congestion, rhinorrhoea, sneezing and itching.
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) or idiopathic rhinitis (VMR) are eligible for randomisation.
6. Subject understands and is willing, able and likely to comply with study procedures and restrictions.
7. Subject must be able to read, comprehend, and record information in English, or native country language. |
|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Significant concomitant medical conditions, defined as:
a) A historical or current evidence of clinically significant uncontrolled disease of any body system (e.g., active tuberculosis, psychological disorders). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or which would confound the interpretation of the study results if the disease/condition exacerbated during the study.
b) 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
c) recent (in the last 6 months) nasal septal or facial cosmetic surgery
d) asthma, with the exception of mild intermittent asthma [NAEPP, 2002] and the [GINA, 2003]. For Canada, see Canadian Asthma Consensus Report, [Boulet, 1999] for guidelines for very mild intermittent asthma). NOTE: Subjects will be allowed to use short-acting inhaled beta2 agonists ONLY on an as needed basis.
e) rhinitis medicamentosa
f) bacterial or viral infection (e.g., common cold) of the upper respiratory tract within two weeks of Visit 1 or during the screening period
g) documented evidence of acute or significant chronic sinusitis, as determined by the individual investigator
h) current or history of glaucoma and/or cataracts or ocular herpes simplex
i) physical impairment that would affect subject’s ability to participate in the study
j) clinical evidence of a Candida infection of the nose or oropharynx
k) 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
l) history of adrenal insufficiency
2. Use of corticosteroids, defined as:
- Intranasal corticosteroid within four weeks prior to Visit 1.
- Inhaled, oral, intramuscular, intravenous, and/or dermatological corticosteroid (with the exception of hydrocortisone cream/ointment, 1% or less) within six months prior to Visit 1.
3. Use of other allergy medications within the timeframe indicated relative to Visit 1
- Intranasal cromolyn within 14 days prior to Visit 1
- Short-acting prescription and OTC antihistamines, including ocular preparations and antihistamines contained in insomnia and ‘nighttime’ pain formulations taken for insomnia, within 3 days prior to Visit 1
- Long-acting antihistamines within 10 days prior to Visit 1: loratadine, desloratadine, fexofenadine, cetirizine
- Long-acting antihistamine, astemizole, within 12 weeks prior to Visit 1
- Oral or intranasal decongestants within 72 hours of Visit 1
- Intranasal, oral or inhaled anticholinergics within 72 hours prior to Visit 1
- Oral antileukotrienes within 72 hours of Visit 1
- Intranasal antihistamine such as Azelastine® within 5 days prior to Visit 1
4. Use of other medications that may affect allergic rhinitis
- Chronic use of concomitant medications, such as tricyclic antidepressants, that would affect assessment of the effectiveness of the study drug.
- Chronic use of long-acting beta-agonists (e.g., salmeterol)
- Subcutaneous omalizumab (Xolair®) within 5 months of Visit 1
- Miacalcin® (intranasal calcitonin) within 72 hours prior to Visit 1
5. Use of immunosuppressive medications 8 weeks prior to Visit 1 and during the study
6. Use of any medications that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including ritonavir and ketoconazole
7. Allergy/Intolerance
- Known hypersensitivity to corticosteroids or any excipients in the product
8. Clinical trial/investigational medication experience
- Has received an investigational study drug for any indication within 30 days or 5 half-lives, whichever is longer, of Visit 1.
9. Positive pregnancy test
- Has a positive urine pregnancy test at screening (Visit 1)
10. 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.
11. Findings of a clinically significant abnormal ECG
12. Findings of a clinically significant laboratory abnormality |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety
- Adverse event reporting
- Routine laboratory tests (haematology and chemistry, including complete blood count with differential and liver function tests) and urinalysis
- Digital centrally-read 12-lead Electrocardiograms (ECG)
- Vital signs (systolic and diastolic blood pressure, heart [pulse]rate)
- Nasal examinations
- 24-hour urinary cortisol assessments
- Slit-lamp and funduscopic examinations, including evaluation of cataract formation, performed by a licensed ophthalmologist or optometrist
- Evaluation for glaucoma and changes in intraocular pressure, performed by a licensed ophthalmologist or optometrist
Pharmacokinetic
- GW685698X plasma concentrations and derived pharmacokinetic parameters using a population PK approach
|
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | Yes |
| 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 | 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.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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