E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Seasonal allergic rhinitis (SAR) |
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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 is to compare the safety and efficacy of GW685698X 100 mcg aqueous nasal spray with vehicle placebo nasal spray in adult and adolescent subjects ≥12 years with SAR. |
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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. 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 under 18 years of age. 2. Outpatient • Subject is treatable on an outpatient basis. 3. Age ≥12 years at Visit 2 4. Male or eligible female 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: • 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 estrogen/progestin or progestin only) • 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 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). • Double barrier method - spermacide plus a mechanical barrier (e.g., spermacide plus a male condom or a spermacide and female diaphragm). Female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A serum pregnancy test will be performed at the screening visit and the final visit. A urine pregnancy test will be performed at the randomization visit. 5. Diagnosis of seasonal allergic rhinitis (SAR) SAR is defined as follows: • Documented clinical history of SAR with seasonal onset and offset of nasal allergy symptoms during each of the last 2 grass pollen seasons and • A positive skin test (by prick method) to a grass pollen that will be abundant in the subjects environment during the course of the study within 12 months prior to Visit 1 or at Visit 1. A positive skin test is defined as a wheal ≥3 mm larger than the diluent control for prick testing. Historical in vitro tests for specific IgE (such as RAST, PRIST) will be allowed as a diagnosis of SAR if conducted less than 12 months prior to Visit 1. Subjects who meet the above criteria and who may also have perennial allergic rhinitis or vasomotor rhinitis are still eligible for randomization. 6. Adequate exposure to the relevant grass pollen • Subject resides within a geographical region where exposure to the pollen that triggers their SAR symptoms and is predicted to be significant during the entire study period. • Subject does not plan to travel outside the geographical region where exposure to the relevant grass pollen is expected to be significant for more than 48 hours of the study period. 7. Ability to comply with study procedures • Subject understands and is willing, able and likely to comply with study procedures and restrictions. 8. Literate • Subject must be able to read, comprehend, and record information as appropriate. |
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E.4 | Principal exclusion criteria |
1. Significant concomitant medical conditions, defined as but not limited to: a. A historical or current evidence of clinically significant uncontrolled disease of any body system (e.g., tuberculosis, psychological disorders, eczema). 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. nasal (e.g., nasal septum), ocular, or throat injury or surgery in the last 3 months d. asthma, with the exception of mild intermittent asthma (NAEPP, 2002 and GINA, 2003). e. rhinitis medicamentosa f. 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 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 safely and fully in the study j. clinical evidence of a Candida infection of the nose 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 2. Use of corticosteroids, defined as: • Intranasal corticosteroid within four weeks prior to Visit 1. • Inhaled, oral, intramuscular, intravenous, ocular, and/or dermatological corticosteroid (with the exception of hydrocortisone cream/ointment, 1% or less) within eight weeks prior to Visit 1. 3. Use of other allergy medications within the timeframe indicated relative to Visit 1 • Intranasal or ocular cromolyn within 14 days prior to Visit 1 • Short-acting prescription and OTC antihistamines, including ocular preparations and antihistamines contained in insomnia and "night time" pain formulations, within 3 days prior to Visit 1 • Long-acting antihistamines within 10 days prior to Visit 1 (e.g., loratadine, desloratadine, fexofenadine, cetirizine) • Intranasal antihistamines (e.g., Astelin⁄ ) within 2 weeks prior to Visit 1 • Oral or intranasal decongestants within 72 hours prior to Visit 1 • Long-acting beta-agonists within 72 hours prior to Visit 1 • Intranasal, oral, or inhaled anticholinergics within 72 hours prior to Visit 1 • Oral antileukotrienes within 72 hours of Visit 1 • Subcutaneous omalizumab (Xolair) within 5 months of Visit 1 • Subjects are not permitted to use any ocular antihistamines, artificial tears, eyewashes/nasal irrigation solutions, allergy homeopathic or herbal preparations, lubricants, sympathomimetic or vasoconstrictor preparations during the screening and treatment periods. No exclusion period prior to screening (Visit 1) is required for these treatments. 4. 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 • Chronic use of long-acting beta-agonists (e.g., salmeterol) • Use of other intranasally administered medications (e.g., calcitonin-salmon) • Use of throat treatments (e.g., such as cough lozenges, throat sprays) 5. Use of immunosuppressive medications 8 weeks prior to screening and during the study 6. Immunotherapy Immunotherapy patients may be enrolled in the study as long as the immunotherapy was not initiated within 30 days of Visit 1 and 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 7. Use of any medications that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including ritonavir and ketoconazole 8. Allergy/Intolerance • Known hypersensitivity to corticosteroids or any excipients in the product 9. Clinical trial/experimental medication experience • Has recent exposure to an investigational study drug within 30 days of Visit 1 • Participation in any other GSK study of intranasal GW685698X aqueous nasal spray 10. Positive pregnancy test or female who is breastfeeding 11. Affiliation with investigational site 12. Current tobacco use 13. Findings of an clinically significant, abnormal ECG 14. Findings of a clinically significant laboratory abnormality 15. Chickenpox or measles • A subject is not eligible if he/she currently has chickenpox or measles, or has been exposed to chickenpox or measles during the last 3 weeks and is non- immune. If a subject develops chickenpox or measles during the study, he/she will be withdrawn from the study. If a non-immune subject is exposed to chickenpox or measles during the study, his/her continuation in the study will be at the discretion of the investigator, taking into consideration the likelihood of developing active disease. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• The primary efficacy endpoint will be the mean change from baseline over the entire treatment period in daily, reflective, total nasal symptom scores (rTNSS). The total nasal symptom score (TNSS) is the sum of 4 individual symptom scores for rhinorrhea, nasal congestion, nasal itching, and sneezing where each symptom is scored on a scale of 0 to 3. The rTNSS is a rating of the severity of symptoms over the previous 12 hours and is performed in the AM (AM rTNSS) and PM (PM rTNSS). The daily rTNSS is the average of the AM rTNSS and PM rTNSS assessments. The baseline TNSS is defined as the average of the daily rTNSS over the 4 consecutive 24-hour periods prior to randomization, including the assessment the morning of randomization prior to study drug administration. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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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 months | 3 |