Allergic rhinitis. MedDRA version: 13.1 Level: LLT Classification code 10001723 Term: Allergic rhinitis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: SB-705498
Product Code: SB-705498
Pharmaceutical Form: Nasal spray, suspension
Current Sponsor code: SB-705498
Other descriptive name: N-(2-bromophenyl)-N'-{(3R)-1-[5-(trifluoromethyl)-2
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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. 1
Exclusion criteria
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 outli
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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.;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.;Timepoint(s) of evaluation of this end point: Primary endpoints: TNSS measured at 1hour post allergen challenge on D8. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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.;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. | — |
Countries
Austria
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline
Outcome results
None listed