| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 13.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001723 |
| E.1.2 | Term | Allergic rhinitis |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| 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 SB-705498 on nasal symptoms elicited by an allergen chamber challenge in subjects with allergic rhinitis when co-administered with FP, compared to FP alone.
Effect of 8 day treatment with intranasal SB-705498 on nasal symptoms elicited by anallergen chamber challenge in subjects with allergic rhinitis compared to placebo. |
|
| E.2.2 | Secondary objectives of the trial |
Effect of 8 day treatment with intranasal SB-705498 when co-administered with FP on symptoms induced by environmental triggers in the natural environment compared to FP alone.
Effect of 8 day treatment with intranasal SB-705498 on symptoms induced by
environmental triggers in the natural environment when compared to placebo.
To determine the systemic exposure following repeat doses of 12mg intranasal SB-
705498.
To determine the systemic exposure following repeat doses of 12mg intranasal SB-
705498 when co administered with FP.
Safety and tolerability of 8 days treatment of SB-705498 alone or when co-administered with FP in subjects with allergic rhinitis. |
|
| 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 ≥4 following the screening allergen challenge
chamber. (Total nasal symptom score is the sum of nasal congestion, rhinorrhoea,
nasal itch and sneeze, each of which are scored on a scale from 0 to 3).
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. Healthy as determined by a responsible and experienced physician, based on a
medical evaluation including medical history, physical examination and laboratory
tests, with the exception of AR and mild asthma not requiring treatment. A subject
with a clinically significant 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.
6. Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
7. 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 estradiol <40 pg/ml (<147 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 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 minimize
the risk of pregnancy at that point. Female subjects must agree to use
contraception until 84 days after the last dose of study medication.
8. Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 84 days after the last dose of study medication.
9. There are no conditions or factors that would make the subject unlikely to be able to stay in the chamber for 4 hours.
10. Body weight ≥ 45kg (female) and ≥50kg (male) and BMI within the range 19 –
29.9kg/m2 (inclusive).
11. Subjects have a screening pre-challenge FEV1 ≥ 80% and a baseline FEV1/FVC ≥
70% of the predicted value.
12. Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
13. Average QTcB < 450 msec; or QTc < 480 msec in subjects with Bundle Branch
Block.
14. 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 |
1. Nasal abnormalities likely to affect the outcome of the study, i.e. nasal septal
perforation, nasal polyps, other nasal malformations.
2. History of frequent nosebleeds.
3. Respiratory disease, other than mild asthma not requiring treatment and associated with normal lung function.
4. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening
5. Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).
6. Positive pre-study drug/alcohol/smoking screen. A minimum list of drugs that will
be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids,
benzodiazepines and methadone.
7. A positive test for HIV antibody.
8. History of regular alcohol consumption within 6 months of the study defined as:
• an average weekly intake of >21 units for males or >14 units for females. One
unit is equivalent to 8g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml)
of wine or 1 (25 ml) measure of spirits.
9. 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).
10. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
11. 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:
• Nasal antihistamines: 72 hours
• Oral antihistamines A (cetirizine, fexofenadine, loratadine, desloratadine): 72
hours
• Oral antihistamines B (all others): 72hours
• Nasal decongestants: 24 hours
• Oral decongestants: 24 hours
• Nasal glucocorticosteroids: 24 hours
• 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.
12. 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.
13. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
14. Pregnant females as determined by positive serum or urine hCG test at screening or
prior to dosing.
15. Lactating females.
16. Unwillingness or inability to follow the procedures outlined in the protocol.
17. Subject is mentally or legally incapacitated.
18. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The effect of 8 day repeat dosing with intranasal 12mg SB-705498 when co-administered with FP compared to FP alone on TNSS and its individual components (nasal congestion, rhinorrhoea, nasal itch and sneeze) elicited by an allergen chamber challenge, 1 hour post dose on Day 8.
The effect of 8 day repeat dosing with intranasal 12mg SB-705498 compared to placebo on Total Nasal Symptom Score (TNSS) and its individual components (nasal congestion, rhinorrhoea, nasal itch and sneeze) elicited by an allergen chamber challenge, 1 hour post dose on Day 8. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoints: TNSS measured at 1hour post allergen challenge on D8.
|
|
| E.5.2 | Secondary end point(s) |
TNSS and its individual components from day 4 to day 8 (post dose prior to challenge) following repeat doses of SB-705498 when co-administered with FP.
TNSS and its individual components from day 4 to day 8 (post dose prior to challenge) following repeat doses of SB-705498 alone.
Active anterior rhinomanometry changes from baseline to day 8, following repeat dosing of SB-705498 when co-administered with FP, at 1 hour post dose.
Active anterior rhinomanometry changes from baseline to day 8, following repeat dosing of SB-705498 alone, at 1 hour post dose.
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) following repeat doses of SB-705498 when co-administered with FP.
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) following repeat doses of SB-705498 alone.
PK on Day 8.
Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology and clinical biochemistry. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints: TNSS on D4-8, Active anterior rhinomanometry on D8 (and baseline), RQLQ on D8 (and baseline), PK on D8 (and pre-dose TP2 and 3 D1), safety parameters throughout the study.
|
|
| 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 | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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.8.3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 5 |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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