Rhinitis
Conditions
Brief summary
This study is designed to look at the affect of SB-705498 on allergic rhinitis symptoms induced by an allergen chamber challenge.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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 allergy, infections or nasal abnormalities. 2. TNSS score of \>=4 following screening allergen challenge chamber. 3. Positive skin prick test for seasonal pollen 4. Positive RAST for seasonal pollen 5. Healthy as determined by responsible physician with the exception of mild asthma and AR 6. Male or female between 18 and 65 years of age inclusive. 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 \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<147 pmol/L) is confirmatory\]. * Child-bearing potential and agrees to use one of the contraception methods listed as instructed. Female subjects must agree to use contraception until 84 days post-last treatment administration. 8. Male subjects with female partners of child-bearing potential must agree to use one contraception as instructed. This must be followed from the time of the first dose of study medication until 84 days post-last treatment administration. 9. Body weight ≥ 50 kg (males) and ≥45kg (females) and BMI within the range 19 - 29.9 kg/m2 (inclusive). 10. Screening pre-challenge FEV1 greater than or equal to 80% and baselines FEV1/FVC greater than or equal to 70% of predicted value. 11. Capable of giving written informed consent. 12. Average QTcB, \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block. 13. AST and ALT \< 2xULN; alkaline phosphatase and bilirubin less than or equal to 1.5xULN
Exclusion criteria
1. Nasal abnormalities likely to affect the outcome of the study, 2. History of frequent nosebleeds. 3. Respiratory disease other than mild asthma 4. A positive pre-study Hepatitis B or Hepatitis C result within 3 months of screening 5. Current or chronic history of liver disease, or known hepatic or biliary abnormalities 6. Positive pre-study drug/alcohol/smoking screen. 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 \>14 drinks for males or \>7 drinks for females. 9. The subject has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product prior to D1. 10. Exposure to more than four new chemical entities within 12 months prior to D1. 11. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days prior to the first dose of study medication. 12. History of sensitivity to any of the study medications, or components 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. Subject is mentally or legally incapacitated. 17. Urine cotinine levels indicative of smoking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Day 8 of each treatment period | Nasal symptoms (nasal congestion, rhinorrhoea, itching and sneezing) were scored on a scale from 0 to 3 where 0= absent symptoms, 3 = severe symptoms. TNSS was calculated as the sum of the response for all 4 individual nasal symptom scores. TNSS ranged from 0 to 12, where 0=absent symptoms, 3=severe symptoms. Higher the score, more severe the symptoms. Weighted mean (WM) of TNSS and its individual components (nasal congestion, rhinorrhoea, itching and sneezing) are presented on Day 8. Weighted mean was calculated over the time interval 0 to 4 hours after start of allergen chamber challenge by calculating the area under the curve of TNSS/component from time of the first observation to time of the last observation (AUC \[tf-t1 hours\]) using the trapezoidal rule, and then dividing by the actual relevant time interval (tf-t1) required by participant to complete the chamber challenge assessments. A Bayesian analysis was conducted to derive the posterior probability for TNSS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR) | Day 8 | Total Nasal Airflow is calculated as the sum of the left nostril and the right nostril airflow values. AAR is a very sensitive method of assessing clinical parameters of nasal obstruction (nasal flow, nasal resistance and nasal flow increase). A participant was instructed to breathe through one nostril while a sensor in the other nostril measured the difference in pre-nasal and choanal pressure. The system was connected to a computer. Nasal flow and nasal resistance were observed at pressure levels of 75, 150 and 300 Pascal. The defined measuring range for the flow was +-1000 milliliter per second (mL/s). Weighted means for total nasal airflow Resistance was calculated by dividing the area under the curve between 1 and 4 hours (via the linear trapezoidal method) by the total duration that the participant took to complete the chamber challenge assessments. |
| Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo | Day 8 | The RQLQ composed of 28 items covering 7 domains of health. Each question is scored on a scale of 0 to 6 (where, 0 = not troubled and 6 = extremely troubled). 7 domains were: Activities (3 items):1, 2, 3;Sleep (3 items): 4, 5, 6; Non-nose/eye symptoms (7 items): 7, 8, 9, 10, 11, 12, 13; Practical Problems (3 items): 14, 15, 16; Nasal Symptoms (4 items): 17, 18, 19, 20; Eye Symptoms (4 items): 21, 22, 23, 24; Emotional (4 items): 25, 26, 27, 28 consisted of total 28 items. Domain activity score = total post-baseline score for individualized activity items answered on both visits divided by total Baseline score for individualized activity items answered on both visits multiplied by the Baseline score for item(s) missing post-baseline. The global RQLQ score was calculated by averaging all 28 item scores, which ranges from 0 to 6 (where, 0 = not troubled and 6 = extremely troubled). Higher scores indicate worsening of symptoms. |
| Area Under Concentration-time Curve (AUC) for SB-705498 on Day 8 | Period 1: Day 1 (post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h), Period 2 and 3: Day 1 (Pre-dose 0.0 h, post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h) | Plasma samples for pharmacokinetic (PK) analysis were drawn at indicated time points of each treatment period. AUC0-t was calculated by the linear trapezoidal method. AUC0-infinity was calculated as the sum of the AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant, where first-order elimination or terminal rate constant was calculated from a semi-log plot of the plasma concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the last three (or more) non-zero plasma concentrations. Values were reported as Least Squares Geometric Means with respective % CV. |
| Maximum Observed Concentration (Cmax) for SB-705498 on Day 8 | Period 1: Day 1 (post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h), Period 2 and 3: Day 1 (Pre-dose 0.0 h, post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h) | Plasma samples for pharmacokinetic analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified. Values were reported as least squares geometric means with respective geometric coefficient of variation (% CV). |
| Mean TNSS and Its Individual Components From Day 4 to Day 8 | pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge [1 hour (hr)] on Day 8 of each treatment period | Nasal symptoms (nasal congestion, rhinorrhoea, itching and sneezing) were scored on a scale from 0 to 3 where 0= absent symptoms, 3 = severe symptoms. TNSS was calculated as the sum of the response for all 4 individual nasal symptom scores. TNSS ranged from 0 to 12, where 0=absent symptoms, 3=severe symptoms. Higher the score, more severe the symptoms. Mean of TNSS and its individual components is presented pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge \[1 hour (hr)\] on Day 8. |
| Change From Baseline in ECG Values: Heart Rate | Baseline and Day 8 of each treatment period | Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated heart rate and measured PQ, QRS, QT, and QTc intervals. Baseline was assessment on Day 1. Change from Baseline was the values at specified time points subtracted by the Baseline value. |
| Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | Baseline and Day 8 of each treatment period | Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated heart rate and measured PQ, QRS, QT, QTc corrected by Bazett's formula (QTcB) and QTc corrected by Fridericia's formula (QTcF). Baseline was assessment on Day 1. Change from Baseline was the values at specified time points subtracted by the Baseline value. |
| Number of Participants With Hematology Parameters of PCI | Up to Week 16 | The PCC range for hematology parameters included white blood cell count, low: 0.67, high 1.82, neutrophil count, low: 0.83, Hemoglobin, male- high 1.03, female- high 1.13, hematocrit, male- high 1.02, female- high 1.17, Platelet Count, low: 0.67, high: 1.57, lymphocytes, low 0.81. Only parameters with PCI values are reported. |
| Number of Participants With Clinical Biochemistry Parameters of PCI | Up to Week 16 | The PCC range for clinical chemistry parameters included albumin, low: 0.86, millimole per liter (mmol)/L, calcium, low: 0.91, high: 1.06, glucose. Low: 0.71, high: 1.41, Potassium, low: 0.86, high: 1.10, Sodium, low: 0.96, high: 1.03, Total CO2, Low: 0.86, high: 1.14, Creatinine, in male, Low: \<75 micromole per liter (μmol/L), high: \>110 μmol/L, female, Low: \<65 μmol/L, high: \>95, Blood Urea Nitrogen (BUN), high: \>1.5xULN mmol/L, Uric Acid, in male, Low: \< 180 μmol/L, high: \> 480 μmol/L, female, Low: \< 120 μmol/L, high: \> 420. Only parameters with PCI values are reported. |
| Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Up to Week 16 | Vital signs assessment included heart rate, blood pressure, and temperature. Criteria for vital sign values meeting potential clinical concern included: systolic blood pressure (SBP) \<85 and \>160 millimeters of mercury (mm Hg), diastolic blood pressure (DBP) \< 45 and \> 100 mm Hg, temperature \<36 and \>37.5 Degree Celsius and heart Rate \<40 and \>110 beats per minute. Only parameters with PCI values are reported. |
Countries
Austria
Participant flow
Recruitment details
A total of 70 male and female participants with a history of allergic rhinitis (AR) were enrolled in this study. Study period was 14 April 2011 to 07 July 2011.
Pre-assignment details
There were 3 study treatment periods each lasting 8 days separated by a washout of 14-20 days. Participants were randomized to 12 different sequences.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A First, Then B, Then D Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered once-daily (OD) in morning for 8 days and 4 actuations per nostril of placebo matching Fluticasone propionate (FP) alone were administered OD in evening for 7 days). Participants received FP 200 microgram (μg) alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received 12 milligrams (mg) SB-705498 co-administered with FP (Treatment D) in Period-3 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 7 |
| Treatment B First, Then A, Then D Eligible participants received Participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-3 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 8 |
| Treatment B, Then D, Then A Eligible participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-2 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days).There was a 14-20 days washout between 2 treatment periods. | 8 |
| Treatment A, Then D, Then B Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-2 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 8 |
| Treatment D, Then A, Then B Eligible participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-1 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 8 |
| Treatment D, Then B, Then A Eligible participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-1 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 8 |
| Treatment A, Then B, Then C Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-3 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 4 |
| Treatment B, Then A, Then C Eligible participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-3 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 4 |
| Treatment B, Then C, Then A Eligible participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-2 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 4 |
| Treatment A, Then C, Then B Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-2 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 3 |
| Treatment C, Then A, Then B Eligible participants received SB-705498 12 mg alone (Treatment C) in Period-1 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 4 |
| Treatment C, Then B, Then A Eligible participants received SB-705498 12 mg alone (Treatment C) in Period-1 (4 actuations per nostril \[each of 1.5mg\] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril \[each of 25μg\] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods. | 4 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period-2 (8 Days) | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment A First, Then B, Then D | Treatment B First, Then A, Then D | Treatment B, Then D, Then A | Treatment A, Then D, Then B | Treatment D, Then A, Then B | Treatment D, Then B, Then A | Treatment A, Then B, Then C | Treatment B, Then A, Then C | Treatment B, Then C, Then A | Treatment A, Then C, Then B | Treatment C, Then A, Then B | Treatment C, Then B, Then A | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 29.6 Years STANDARD_DEVIATION 5.65 | 29.6 Years STANDARD_DEVIATION 9.24 | 28.0 Years STANDARD_DEVIATION 5.07 | 28.5 Years STANDARD_DEVIATION 9.2 | 28.5 Years STANDARD_DEVIATION 6.46 | 27.8 Years STANDARD_DEVIATION 6.34 | 24.5 Years STANDARD_DEVIATION 3.11 | 32.5 Years STANDARD_DEVIATION 10.54 | 25.3 Years STANDARD_DEVIATION 1.5 | 24.0 Years STANDARD_DEVIATION 1 | 28.3 Years STANDARD_DEVIATION 6.29 | 26.8 Years STANDARD_DEVIATION 11.03 | 28.1 Years STANDARD_DEVIATION 6.86 |
| Race/Ethnicity, Customized American Indian or Alaskan Native Wh-Wh/Ca/Eu H | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - South East Asian H | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Wh - Arabic/North African H | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White(Wh)-Wh/Caucasian(Ca)/European(Eu)Heritage(H) | 7 Participants | 8 Participants | 8 Participants | 7 Participants | 7 Participants | 7 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 67 Participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 33 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 2 Participants | 5 Participants | 4 Participants | 4 Participants | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 68 | 0 / 69 | 0 / 23 | 0 / 47 |
| other Total, other adverse events | 24 / 68 | 28 / 69 | 13 / 23 | 19 / 47 |
| serious Total, serious adverse events | 0 / 68 | 0 / 69 | 0 / 23 | 0 / 47 |
Outcome results
Primary
Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8
Nasal symptoms (nasal congestion, rhinorrhoea, itching and sneezing) were scored on a scale from 0 to 3 where 0= absent symptoms, 3 = severe symptoms. TNSS was calculated as the sum of the response for all 4 individual nasal symptom scores. TNSS ranged from 0 to 12, where 0=absent symptoms, 3=severe symptoms. Higher the score, more severe the symptoms. Weighted mean (WM) of TNSS and its individual components (nasal congestion, rhinorrhoea, itching and sneezing) are presented on Day 8. Weighted mean was calculated over the time interval 0 to 4 hours after start of allergen chamber challenge by calculating the area under the curve of TNSS/component from time of the first observation to time of the last observation (AUC \[tf-t1 hours\]) using the trapezoidal rule, and then dividing by the actual relevant time interval (tf-t1) required by participant to complete the chamber challenge assessments. A Bayesian analysis was conducted to derive the posterior probability for TNSS.
Time frame: Day 8 of each treatment period
Population: All subjects population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Nasal itching score WM | 1.67 Score on scale | Standard Deviation 0.76 |
| Placebo | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Nasal congestion scoreWM | 1.80 Score on scale | Standard Deviation 0.653 |
| Placebo | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Sneezing score WM | 1.39 Score on scale | Standard Deviation 0.763 |
| Placebo | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Rhinorrhoea score WM | 1.67 Score on scale | Standard Deviation 0.693 |
| Placebo | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | TNSS WM | 6.53 Score on scale | Standard Deviation 2.3 |
| FP 200 μg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Rhinorrhoea score WM | 0.94 Score on scale | Standard Deviation 0.726 |
| FP 200 μg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Nasal itching score WM | 0.94 Score on scale | Standard Deviation 0.708 |
| FP 200 μg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Sneezing score WM | 0.62 Score on scale | Standard Deviation 0.573 |
| FP 200 μg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Nasal congestion scoreWM | 1.15 Score on scale | Standard Deviation 0.792 |
| FP 200 μg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | TNSS WM | 3.65 Score on scale | Standard Deviation 2.36 |
| SB-705498 12 mg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Rhinorrhoea score WM | 1.75 Score on scale | Standard Deviation 0.697 |
| SB-705498 12 mg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | TNSS WM | 6.57 Score on scale | Standard Deviation 2.418 |
| SB-705498 12 mg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Nasal congestion scoreWM | 1.82 Score on scale | Standard Deviation 0.648 |
| SB-705498 12 mg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Nasal itching score WM | 1.57 Score on scale | Standard Deviation 0.886 |
| SB-705498 12 mg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Sneezing score WM | 1.43 Score on scale | Standard Deviation 0.785 |
| SB-705498 + FP 12 mg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Nasal itching score WM | 1.17 Score on scale | Standard Deviation 0.699 |
| SB-705498 + FP 12 mg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Nasal congestion scoreWM | 1.18 Score on scale | Standard Deviation 0.715 |
| SB-705498 + FP 12 mg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | TNSS WM | 4.14 Score on scale | Standard Deviation 2.243 |
| SB-705498 + FP 12 mg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Rhinorrhoea score WM | 1.05 Score on scale | Standard Deviation 0.687 |
| SB-705498 + FP 12 mg | Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 | Sneezing score WM | 0.74 Score on scale | Standard Deviation 0.56 |
Secondary
Area Under Concentration-time Curve (AUC) for SB-705498 on Day 8
Plasma samples for pharmacokinetic (PK) analysis were drawn at indicated time points of each treatment period. AUC0-t was calculated by the linear trapezoidal method. AUC0-infinity was calculated as the sum of the AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant, where first-order elimination or terminal rate constant was calculated from a semi-log plot of the plasma concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the last three (or more) non-zero plasma concentrations. Values were reported as Least Squares Geometric Means with respective % CV.
Time frame: Period 1: Day 1 (post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h), Period 2 and 3: Day 1 (Pre-dose 0.0 h, post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h)
Population: The 'Pharmacokinetic Population' is defined as participants in the 'All Subjects' population for whom a pharmacokinetic sample was obtained and analyzed. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under Concentration-time Curve (AUC) for SB-705498 on Day 8 | 588.26 nanograms*hour per mililiter (ng.h/mL) | Geometric Coefficient of Variation 71.4 |
| FP 200 μg | Area Under Concentration-time Curve (AUC) for SB-705498 on Day 8 | 608.84 nanograms*hour per mililiter (ng.h/mL) | Geometric Coefficient of Variation 74.2 |
Secondary
Change From Baseline in ECG Values: Heart Rate
Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated heart rate and measured PQ, QRS, QT, and QTc intervals. Baseline was assessment on Day 1. Change from Baseline was the values at specified time points subtracted by the Baseline value.
Time frame: Baseline and Day 8 of each treatment period
Population: All subjects population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in ECG Values: Heart Rate | -0.2 beats per minute (bpm) | Standard Deviation 11.32 |
| FP 200 μg | Change From Baseline in ECG Values: Heart Rate | -4.7 beats per minute (bpm) | Standard Deviation 10.8 |
| SB-705498 12 mg | Change From Baseline in ECG Values: Heart Rate | -4.8 beats per minute (bpm) | Standard Deviation 8.09 |
| SB-705498 + FP 12 mg | Change From Baseline in ECG Values: Heart Rate | -2.6 beats per minute (bpm) | Standard Deviation 11.19 |
Secondary
Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF
Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated heart rate and measured PQ, QRS, QT, QTc corrected by Bazett's formula (QTcB) and QTc corrected by Fridericia's formula (QTcF). Baseline was assessment on Day 1. Change from Baseline was the values at specified time points subtracted by the Baseline value.
Time frame: Baseline and Day 8 of each treatment period
Population: All subjects population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QTcB | -3.6 Milliseconds (msec) | Standard Deviation 17.3 |
| Placebo | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QRS Duration | 0.8 Milliseconds (msec) | Standard Deviation 6.3 |
| Placebo | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QTcF | -2.9 Milliseconds (msec) | Standard Deviation 13.16 |
| Placebo | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QT Interval | -1.5 Milliseconds (msec) | Standard Deviation 21.47 |
| Placebo | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | PR Interval | 2.7 Milliseconds (msec) | Standard Deviation 8.31 |
| FP 200 μg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QT Interval | 4.6 Milliseconds (msec) | Standard Deviation 22.12 |
| FP 200 μg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QTcB | -9.3 Milliseconds (msec) | Standard Deviation 18.44 |
| FP 200 μg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QTcF | -4.4 Milliseconds (msec) | Standard Deviation 13.37 |
| FP 200 μg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QRS Duration | 2.2 Milliseconds (msec) | Standard Deviation 5.52 |
| FP 200 μg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | PR Interval | -1.2 Milliseconds (msec) | Standard Deviation 9.38 |
| SB-705498 12 mg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QT Interval | -0.3 Milliseconds (msec) | Standard Deviation 17.5 |
| SB-705498 12 mg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | PR Interval | 4.5 Milliseconds (msec) | Standard Deviation 9.29 |
| SB-705498 12 mg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QRS Duration | 0.8 Milliseconds (msec) | Standard Deviation 5.92 |
| SB-705498 12 mg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QTcB | -13.9 Milliseconds (msec) | Standard Deviation 20.79 |
| SB-705498 12 mg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QTcF | -9.0 Milliseconds (msec) | Standard Deviation 16.53 |
| SB-705498 + FP 12 mg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QTcB | -4.1 Milliseconds (msec) | Standard Deviation 21.1 |
| SB-705498 + FP 12 mg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QRS Duration | -0.2 Milliseconds (msec) | Standard Deviation 5.05 |
| SB-705498 + FP 12 mg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | PR Interval | 0.4 Milliseconds (msec) | Standard Deviation 9.73 |
| SB-705498 + FP 12 mg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QT Interval | 2.5 Milliseconds (msec) | Standard Deviation 17.93 |
| SB-705498 + FP 12 mg | Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF | QTcF | -1.9 Milliseconds (msec) | Standard Deviation 13.33 |
Secondary
Maximum Observed Concentration (Cmax) for SB-705498 on Day 8
Plasma samples for pharmacokinetic analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified. Values were reported as least squares geometric means with respective geometric coefficient of variation (% CV).
Time frame: Period 1: Day 1 (post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h), Period 2 and 3: Day 1 (Pre-dose 0.0 h, post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h)
Population: Pharmacokinetic Population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Concentration (Cmax) for SB-705498 on Day 8 | 145.958 nanograms per mililiter (ng/mL) | Geometric Coefficient of Variation 68.8 |
| FP 200 μg | Maximum Observed Concentration (Cmax) for SB-705498 on Day 8 | 154.231 nanograms per mililiter (ng/mL) | Geometric Coefficient of Variation 71 |
Secondary
Mean TNSS and Its Individual Components From Day 4 to Day 8
Nasal symptoms (nasal congestion, rhinorrhoea, itching and sneezing) were scored on a scale from 0 to 3 where 0= absent symptoms, 3 = severe symptoms. TNSS was calculated as the sum of the response for all 4 individual nasal symptom scores. TNSS ranged from 0 to 12, where 0=absent symptoms, 3=severe symptoms. Higher the score, more severe the symptoms. Mean of TNSS and its individual components is presented pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge \[1 hour (hr)\] on Day 8.
Time frame: pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge [1 hour (hr)] on Day 8 of each treatment period
Population: All subjects population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 4, pre-pm dose | 3.6 Score on a scale | Standard Deviation 2.47 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 8, pre-challenge (1hr) | 0.3 Score on a scale | Standard Deviation 0.51 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 6, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.84 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 6, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.8 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 5, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.81 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 6, pre-pm dose | 3.3 Score on a scale | Standard Deviation 2.45 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 5, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.85 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 7, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.69 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 8, pre-challenge (1hr) | 0.6 Score on a scale | Standard Deviation 0.69 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 8, pre-challenge (1hr) | 2.0 Score on a scale | Standard Deviation 1.88 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 7, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.65 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 8, pre-challenge | 0.7 Score on a scale | Standard Deviation 0.67 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 7, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.75 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 5, pre-pm dose | 3.6 Score on a scale | Standard Deviation 2.58 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 4, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.78 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 4, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.71 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 4, pre-pm dose | 1.0 Score on a scale | Standard Deviation 0.81 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 4, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.85 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 7, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.8 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 5, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.75 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 6, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.82 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 7, pre-pm dose | 3.2 Score on a scale | Standard Deviation 2.26 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 8, pre-challenge (1hr | 0.5 Score on a scale | Standard Deviation 0.65 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 6, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.73 |
| Placebo | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 5, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.82 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 6, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.65 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 7, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.62 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 7, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.62 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 8, pre-challenge (1hr) | 0.3 Score on a scale | Standard Deviation 0.59 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 6, pre-pm dose | 0.3 Score on a scale | Standard Deviation 0.58 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 4, pre-pm dose | 0.5 Score on a scale | Standard Deviation 0.66 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 5, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.63 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 8, pre-challenge (1hr) | 1.3 Score on a scale | Standard Deviation 1.6 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 5, pre-pm dose | 2.0 Score on a scale | Standard Deviation 2.24 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 6, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.57 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 4, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.69 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 4, pre-pm dose | 2.4 Score on a scale | Standard Deviation 2.2 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 5, pre-pm dose | 0.7 Score on a scale | Standard Deviation 0.7 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 5, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.67 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 6, pre-pm dose | 0.7 Score on a scale | Standard Deviation 0.74 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 7, pre-pm dose | 0.6 Score on a scale | Standard Deviation 0.62 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 6, pre-pm dose | 1.8 Score on a scale | Standard Deviation 2.03 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 4, pre-pm dose | 0.5 Score on a scale | Standard Deviation 0.68 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 8, pre-challenge | 0.6 Score on a scale | Standard Deviation 0.67 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 8, pre-challenge (1hr) | 0.1 Score on a scale | Standard Deviation 0.26 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 4, pre-pm dose | 0.6 Score on a scale | Standard Deviation 0.76 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 7, pre-pm dose | 0.3 Score on a scale | Standard Deviation 0.55 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 8, pre-challenge (1hr | 0.3 Score on a scale | Standard Deviation 0.6 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 5, pre-pm dose | 0.5 Score on a scale | Standard Deviation 0.78 |
| FP 200 μg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 7, pre-pm dose | 1.7 Score on a scale | Standard Deviation 1.9 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 4, pre-pm dose | 0.7 Score on a scale | Standard Deviation 0.71 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 4, pre-pm dose | 3.3 Score on a scale | Standard Deviation 2.65 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 5, pre-pm dose | 2.9 Score on a scale | Standard Deviation 2.6 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 6, pre-pm dose | 2.8 Score on a scale | Standard Deviation 2.74 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 7, pre-pm dose | 2.2 Score on a scale | Standard Deviation 2.37 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 8, pre-challenge (1hr) | 1.9 Score on a scale | Standard Deviation 1.52 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 4, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.95 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 5, pre-pm dose | 0.7 Score on a scale | Standard Deviation 0.88 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 6, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.83 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 7, pre-pm dose | 0.7 Score on a scale | Standard Deviation 0.82 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 8, pre-challenge | 0.6 Score on a scale | Standard Deviation 0.59 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 4, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.87 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 5, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.9 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 6, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.9 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 7, pre-pm dose | 0.6 Score on a scale | Standard Deviation 0.78 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 8, pre-challenge (1hr) | 0.6 Score on a scale | Standard Deviation 0.66 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 5, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.66 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 6, pre-pm dose | 0.5 Score on a scale | Standard Deviation 0.73 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 7, pre-pm dose | 0.3 Score on a scale | Standard Deviation 0.65 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 8, pre-challenge (1hr | 0.3 Score on a scale | Standard Deviation 0.49 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 4, pre-pm dose | 0.9 Score on a scale | Standard Deviation 0.87 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 5, pre-pm dose | 0.8 Score on a scale | Standard Deviation 0.83 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 6, pre-pm dose | 0.7 Score on a scale | Standard Deviation 0.92 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 7, pre-pm dose | 0.5 Score on a scale | Standard Deviation 0.73 |
| SB-705498 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 8, pre-challenge (1hr) | 0.4 Score on a scale | Standard Deviation 0.58 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 7, pre-pm dose | 0.5 Score on a scale | Standard Deviation 0.72 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 5, pre-pm dose | 0.5 Score on a scale | Standard Deviation 0.66 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 4, pre-pm dose | 0.5 Score on a scale | Standard Deviation 0.65 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 8, pre-challenge (1hr) | 0.1 Score on a scale | Standard Deviation 0.31 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 8, pre-challenge (1hr | 0.3 Score on a scale | Standard Deviation 0.55 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 8, pre-challenge | 0.4 Score on a scale | Standard Deviation 0.58 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 7, pre-pm dose | 0.6 Score on a scale | Standard Deviation 0.65 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 7, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.61 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 4, pre-pm dose | 0.6 Score on a scale | Standard Deviation 0.68 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 6, pre-pm dose | 0.6 Score on a scale | Standard Deviation 0.68 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 5, pre-pm dose | 0.6 Score on a scale | Standard Deviation 0.64 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 5, pre-pm dose | 2.3 Score on a scale | Standard Deviation 2.1 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 5, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.65 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal congestion score code,Day 4, pre-pm dose | 0.7 Score on a scale | Standard Deviation 0.65 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 8, pre-challenge (1hr) | 1.1 Score on a scale | Standard Deviation 1.45 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 4, pre-pm dose | 2.6 Score on a scale | Standard Deviation 1.94 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Sneezing score code,Day 6, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.68 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 5, pre-pm dose | 0.7 Score on a scale | Standard Deviation 0.75 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 4, pre-pm dose | 0.7 Score on a scale | Standard Deviation 0.71 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 8, pre-challenge (1hr) | 0.3 Score on a scale | Standard Deviation 0.5 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 7, pre-pm dose | 1.9 Score on a scale | Standard Deviation 2.12 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Nasal itching score code,Day 6, pre-pm dose | 0.5 Score on a scale | Standard Deviation 0.72 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 7, pre-pm dose | 0.4 Score on a scale | Standard Deviation 0.69 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | Rhinorrhoea score code,Day 6, pre-pm dose | 0.6 Score on a scale | Standard Deviation 0.62 |
| SB-705498 + FP 12 mg | Mean TNSS and Its Individual Components From Day 4 to Day 8 | TNSS,Day 6, pre-pm dose | 2.0 Score on a scale | Standard Deviation 2.03 |
Secondary
Number of Participants With Clinical Biochemistry Parameters of PCI
The PCC range for clinical chemistry parameters included albumin, low: 0.86, millimole per liter (mmol)/L, calcium, low: 0.91, high: 1.06, glucose. Low: 0.71, high: 1.41, Potassium, low: 0.86, high: 1.10, Sodium, low: 0.96, high: 1.03, Total CO2, Low: 0.86, high: 1.14, Creatinine, in male, Low: \<75 micromole per liter (μmol/L), high: \>110 μmol/L, female, Low: \<65 μmol/L, high: \>95, Blood Urea Nitrogen (BUN), high: \>1.5xULN mmol/L, Uric Acid, in male, Low: \< 180 μmol/L, high: \> 480 μmol/L, female, Low: \< 120 μmol/L, high: \> 420. Only parameters with PCI values are reported.
Time frame: Up to Week 16
Population: All subjects population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinical Biochemistry Parameters of PCI | Creatinine,Low | 19 Participants |
| Placebo | Number of Participants With Clinical Biochemistry Parameters of PCI | Creatinine,High | 2 Participants |
| Placebo | Number of Participants With Clinical Biochemistry Parameters of PCI | Aspartate Amino Transferase,High | 1 Participants |
| Placebo | Number of Participants With Clinical Biochemistry Parameters of PCI | Potassium,High | 2 Participants |
| Placebo | Number of Participants With Clinical Biochemistry Parameters of PCI | Uric acid,High | 1 Participants |
| Placebo | Number of Participants With Clinical Biochemistry Parameters of PCI | Gamma Glutamyl Transferase,High | 1 Participants |
| Placebo | Number of Participants With Clinical Biochemistry Parameters of PCI | Total Bilirubin,High | 1 Participants |
| Placebo | Number of Participants With Clinical Biochemistry Parameters of PCI | Alanine Amino Transferase,High | 0 Participants |
| FP 200 μg | Number of Participants With Clinical Biochemistry Parameters of PCI | Gamma Glutamyl Transferase,High | 1 Participants |
| FP 200 μg | Number of Participants With Clinical Biochemistry Parameters of PCI | Uric acid,High | 0 Participants |
| FP 200 μg | Number of Participants With Clinical Biochemistry Parameters of PCI | Creatinine,High | 2 Participants |
| FP 200 μg | Number of Participants With Clinical Biochemistry Parameters of PCI | Alanine Amino Transferase,High | 2 Participants |
| FP 200 μg | Number of Participants With Clinical Biochemistry Parameters of PCI | Total Bilirubin,High | 1 Participants |
| FP 200 μg | Number of Participants With Clinical Biochemistry Parameters of PCI | Potassium,High | 4 Participants |
| FP 200 μg | Number of Participants With Clinical Biochemistry Parameters of PCI | Aspartate Amino Transferase,High | 1 Participants |
| FP 200 μg | Number of Participants With Clinical Biochemistry Parameters of PCI | Creatinine,Low | 25 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Total Bilirubin,High | 1 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Aspartate Amino Transferase,High | 1 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Potassium,High | 2 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Uric acid,High | 1 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Gamma Glutamyl Transferase,High | 2 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Alanine Amino Transferase,High | 0 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Creatinine,Low | 6 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Creatinine,High | 1 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Aspartate Amino Transferase,High | 0 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Potassium,High | 5 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Creatinine,High | 2 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Creatinine,Low | 14 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Uric acid,High | 1 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Alanine Amino Transferase,High | 0 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Total Bilirubin,High | 1 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Clinical Biochemistry Parameters of PCI | Gamma Glutamyl Transferase,High | 1 Participants |
Secondary
Number of Participants With Hematology Parameters of PCI
The PCC range for hematology parameters included white blood cell count, low: 0.67, high 1.82, neutrophil count, low: 0.83, Hemoglobin, male- high 1.03, female- high 1.13, hematocrit, male- high 1.02, female- high 1.17, Platelet Count, low: 0.67, high: 1.57, lymphocytes, low 0.81. Only parameters with PCI values are reported.
Time frame: Up to Week 16
Population: All subjects population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Hematology Parameters of PCI | Total Neutrophils,low | 7 Participants |
| Placebo | Number of Participants With Hematology Parameters of PCI | Hemoglobin,high | 0 Participants |
| Placebo | Number of Participants With Hematology Parameters of PCI | Hematocrit,high | 0 Participants |
| FP 200 μg | Number of Participants With Hematology Parameters of PCI | Total Neutrophils,low | 9 Participants |
| FP 200 μg | Number of Participants With Hematology Parameters of PCI | Hemoglobin,high | 0 Participants |
| FP 200 μg | Number of Participants With Hematology Parameters of PCI | Hematocrit,high | 0 Participants |
| SB-705498 12 mg | Number of Participants With Hematology Parameters of PCI | Hematocrit,high | 1 Participants |
| SB-705498 12 mg | Number of Participants With Hematology Parameters of PCI | Total Neutrophils,low | 2 Participants |
| SB-705498 12 mg | Number of Participants With Hematology Parameters of PCI | Hemoglobin,high | 1 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Hematology Parameters of PCI | Total Neutrophils,low | 4 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Hematology Parameters of PCI | Hemoglobin,high | 0 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Hematology Parameters of PCI | Hematocrit,high | 0 Participants |
Secondary
Number of Participants With Vital Signs of Potential Clinical Importance (PCI)
Vital signs assessment included heart rate, blood pressure, and temperature. Criteria for vital sign values meeting potential clinical concern included: systolic blood pressure (SBP) \<85 and \>160 millimeters of mercury (mm Hg), diastolic blood pressure (DBP) \< 45 and \> 100 mm Hg, temperature \<36 and \>37.5 Degree Celsius and heart Rate \<40 and \>110 beats per minute. Only parameters with PCI values are reported.
Time frame: Up to Week 16
Population: All Subjects population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature,Low,period 3 | 2 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature,Low,Follow up | 2 Participants |
| FP 200 μg | Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature,Low,Follow up | 1 Participants |
| FP 200 μg | Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature,Low,period 3 | 0 Participants |
| SB-705498 12 mg | Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature,Low,period 3 | 0 Participants |
| SB-705498 12 mg | Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature,Low,Follow up | 0 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature,Low,period 3 | 0 Participants |
| SB-705498 + FP 12 mg | Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature,Low,Follow up | 0 Participants |
Secondary
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo
The RQLQ composed of 28 items covering 7 domains of health. Each question is scored on a scale of 0 to 6 (where, 0 = not troubled and 6 = extremely troubled). 7 domains were: Activities (3 items):1, 2, 3;Sleep (3 items): 4, 5, 6; Non-nose/eye symptoms (7 items): 7, 8, 9, 10, 11, 12, 13; Practical Problems (3 items): 14, 15, 16; Nasal Symptoms (4 items): 17, 18, 19, 20; Eye Symptoms (4 items): 21, 22, 23, 24; Emotional (4 items): 25, 26, 27, 28 consisted of total 28 items. Domain activity score = total post-baseline score for individualized activity items answered on both visits divided by total Baseline score for individualized activity items answered on both visits multiplied by the Baseline score for item(s) missing post-baseline. The global RQLQ score was calculated by averaging all 28 item scores, which ranges from 0 to 6 (where, 0 = not troubled and 6 = extremely troubled). Higher scores indicate worsening of symptoms.
Time frame: Day 8
Population: All subjects population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo | 1.67 Score on a scale | Standard Error 0.119 |
| FP 200 μg | Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo | 0.99 Score on a scale | Standard Error 0.118 |
| SB-705498 12 mg | Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo | 1.66 Score on a scale | Standard Error 0.177 |
| SB-705498 + FP 12 mg | Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo | 1.14 Score on a scale | Standard Error 0.135 |
90% CI: [-0.87, -0.49]
90% CI: [-0.3, 0.27]
90% CI: [-0.74, -0.31]
90% CI: [-0.06, 0.37]
Secondary
Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR)
Total Nasal Airflow is calculated as the sum of the left nostril and the right nostril airflow values. AAR is a very sensitive method of assessing clinical parameters of nasal obstruction (nasal flow, nasal resistance and nasal flow increase). A participant was instructed to breathe through one nostril while a sensor in the other nostril measured the difference in pre-nasal and choanal pressure. The system was connected to a computer. Nasal flow and nasal resistance were observed at pressure levels of 75, 150 and 300 Pascal. The defined measuring range for the flow was +-1000 milliliter per second (mL/s). Weighted means for total nasal airflow Resistance was calculated by dividing the area under the curve between 1 and 4 hours (via the linear trapezoidal method) by the total duration that the participant took to complete the chamber challenge assessments.
Time frame: Day 8
Population: All subjects population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR) | 306.99 Milliliters per second (mL/s) | Standard Error 17.255 |
| FP 200 μg | Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR) | 388.34 Milliliters per second (mL/s) | Standard Error 17.207 |
| SB-705498 12 mg | Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR) | 299.68 Milliliters per second (mL/s) | Standard Error 22.806 |
| SB-705498 + FP 12 mg | Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR) | 379.40 Milliliters per second (mL/s) | Standard Error 18.783 |
Comparison: Placebo versus FP 200 μg,Nasal Airflow resistance Total WM,0-4 hr90% CI: [60.54, 102.15]
Comparison: Placebo versus FP 12 mg SB-705498 , Nasal Airflow resistance Total WM, 0-4 hr90% CI: [-39.7, 25.05]
Comparison: Placebo versus SB-705498 + FP 12 mg, Nasal Airflow resistance Total WM, 0-4 hr90% CI: [48.28, 96.52]
Comparison: FP 200 μg versus SB-705498 + FP 12 mg, Nasal Airflow resistance Total WM, 0-4 hr90% CI: [-33.1, 15.22]