| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Seasonal Allergic Rhinitis |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039776 |
| E.1.2 | Term | Seasonal allergic rhinitis |
|
| 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 |
Investigate the effect of repeat intranasal doses of GSK1004723 vs. placebo on prevention of nasal symptoms of allergic rhinitis provoked by allergen and assessed during 6 hours in the environmental challenge chamber (1h post-GSK1004723 dose).
Investigate the effect of repeat oral doses of GSK835726 vs. placebo on prevention of nasal symptoms of allergic rhinitis provoked by allergen and assessed during 6 hours in the environmental challenge chamber (1h post-GSK835726 dose). |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria
apply:
1. The subject is healthy with the exception of seasonal allergic rhinitis. The subject may also have mild asthma. Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
2. Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
3. 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; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and oestradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 of the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
•Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimise the risk of pregnancy at that point. Female subjects must agree to use contraception until 4 days after final dose of study medication.
4. Male subjects must agree to use one of the contraception methods listed in Section 8.1 of the protocol. This criterion must be followed from the time of the first dose of study medication until 4 days after final dose of study medication.
5. Body weight ≥ 50 kg and BMI within the range 19 - 32kg/m2.
6. The subject has a history of seasonal allergic rhinitis
7. The subject exhibits a moderate response to 4000 grass pollen grains/m3 within 2h in the Environmental Challenge Chamber, which is defined as a nasal symptom score of ≥6 at least once (Nasal symptom score is the sum of nasal blockage, rhinorrhoea, itch and sneeze, each of which will be scored on a scale from 0 to 3).
8. The subject has a positive skin prick test (wheal ≥ 3mm) for Dactylis glomerata (at
or within the 12 months preceding the screening visit).
9. The subject has a baseline FEV1 ≥ 80% predicted.
10. A non-smoker for at least the past 12 months with a pack history of <10 pack years.
Pack years = (No cigarettes smoked/day divided by 20) x No of years smoked
11. There are no conditions or factors that would make the subject unlikely to be able to stay in the chamber for 6 hours.
12. The subject is capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
13. The subject is available to complete all study measurements.
14. Able to use the intranasal Nasal Spray satisfactorily.
15. AST and ALT < 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). |
|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria
apply:
1. On examination the subject is found to have any structural nasal abnormalities or nasal polyposis, a history of frequent nosebleeds, recent nasal surgery or recent (within 3 weeks) or ongoing upper respiratory tract infection which in the responsible Physician’s opinion renders the subject unsuitable for participation in the
study.
2. Any respiratory disease other than mild stable intermittent asthma [Global Initiative for Asthma (GINA), 2007] that is controlled with occasional use of as-needed short-acting beta-agonists and associated with normal lung function.
3. The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication. The subject is concurrently participating in another clinical study in which the subject is or will be exposed to an investigational or a non-investigational drug or nasal spray.
4. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
5. The subject has donated a unit of blood (450mL) within the previous 3 months or intends to donate within 3 months of completing the study.
6. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John'sWort) 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 sponsor the medication will not interfere with the study procedures or compromise subject safety.
7. 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 physician responsible, contraindicates their participation.
8. History of alcohol/drug abuse or dependence within 12 months of the study.
9. Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
10. The subject has a positive pre-study urine drug screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
11. Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
12. Lactating females.
13. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
14. The subject has tested positive for HIV antibodies.
15. The subject is at risk of non-compliance with the study procedures/restrictions.
16. Subjects showing clinical symptoms of perennial allergic rhinitis.
17. History of a respiratory tract infection and/or exacerbation of asthma within 3 weeks before the screening.
18. Administration of oral, injectable or dermal corticosteroids within 8 weeks or intranasal and/or inhaled corticosteroids 3 weeks prior to the screening visit.
19. Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease or pulmonary disease (including but not confined to chronic bronchitis, emphysema, tuberculosis, bronchiectasis or cystic fibrosis).
20. Known hypersensitivity, allergic reactions or intolerance to study drug or any of the other ingredients.
21. Specific Immunotherapy (SIT) within the last two years prior to screening.
22. There is a risk of non-compliance with study procedures. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Weighted mean TNSS (sneeze, itch, rhinorrhoea and nasal blockage) 1-6h post start of allergen challenge (2-7h post-dose) on Day 3. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| 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 | 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) | Yes |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
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