Rhinitis
Conditions
Brief summary
The purpose of this study is to assess the pharmacodynamic (PD) effects (Total Symptom Score (TSS) and its individual components: rhinorrhoea, nasal congestion, post-nasal drip) of intranasal, repeat dose SB-705498 in non-allergic rhinitis (NAR) patients elicited by a cold dry air challenge in an environmental exposure chamber (EEC). SB-705498 is a selective antagonist of the transient receptor potential vanilloid-1 (TRPV1) ligand gated ion channel. TRPV1 is a cation permeable ion channel that can be activated by several physiological factors, such as heat, protons (pH), osmotic stress, eicosanoid derivatives, anandamide, and by products of inflammation, such as histamine, prostaglandins and bradykinin. In the nose, the local TRPV1 expressing sensory C-fibres are thought to play a key role in the development of nasal hyper-responsiveness to environmental provocateurs. It has been proposed that blocking the nasal sensory nerve stimulation may control nasal hyper-responsiveness and therefore prevent the induction of rhinitis symptoms. In this context, preclinical evidence supports that targeting TRPV1 by SB-705498 may be an attractive option. In this study NAR patients will be randomised, in a double blind, placebo controlled cross over design to receive 14 day repeat doses of 12mg intra-nasal SB-705498 once daily. Whilst dosing at home, subjects will record symptom scores to document their symptoms. In addition, during visits to the clinical unit, acoustic rhinometry, quality of life questionnaires and safety assessments will be monitored.
Interventions
DRUGSB-705498
12mg intra nasal
DRUGPlacebo
Placebo intra nasal
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
Deviations from inclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Diagnosis of NAR, as determined by the presence of perennial rhinitis symptoms that last for several months per year, for more than 1 year and are not attributed to allergy, infections or nasal abnormalities. Positive history of rhinitis symptoms triggered by environmental provocateurs (e.g. weather changes, irritants, air pollution etc), but not allergens. 2. Normal levels of total plasma IgE and negative allergy skin or Rast tests to common aeroallergens. 3. Male or female between 18 and 65 years of age inclusive. 4. 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 post-last treatment administration. 5. 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 post-last treatment administration. 6. Body weight ≥ 50 kg (males) and ≥45kg (females) and BMI within the range 19 - 29.9 kg/m2 (inclusive). 7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 8. Available to complete all the required study measurements. 9. Single QTc, \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block. 10. The subject must demonstrate at screening TSS ≥ 4 (on a 9 point scale) at screening visits 1 and 2. 11. AST and ALT \< 2xULN; alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
Exclusion criteria
Deviations from
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) Cold Dry Air (CDA) Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Day 14 to Day 15 of each period (Day 14, 24 h post- dose was done on Day 15) | TSS was calculated based on a CDA challenge, done for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree Celsius (C), \<15% relative humidity and 5+/-3 feet per second (ft/sec) air velocity, 1 h and 24 h post dose on Day 14 (Day 15). TSS was calculated as the sum of the response for 3 components of nasal congestion, rhinorrhoea and post nasal drip. It was rated on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). TSS score ranges from 0-9 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Weighted mean (WM) for TSS was calculated over the time interval 0 to 60 minute (m) after start of CDA challenge by calculating area under the curve (AUC) of the TSS via the linear trapezoidal method then dividing by the total duration that the participant took to complete CDA challenge assessments. WM is reported as least square (LS) mean. |
| Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Day 14 to Day 15 of each period (Day 14, 24 h post- dose was done on Day 15) | The individual components of TSS was calculated based on a CDA challenge, done for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree C, \<15% relative humidity and 5+/-3 ft/sec air velocity, 1 h and 24 h post dose on Day 14 (Day 15). The individual component of TSS nasal symptoms were nasal congestion, rhinorrhoea (runny nose), and post nasal drip It was rated on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). The scores of the individual components of TSS ranges from 0-3 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. WM for TSS was calculated over the time interval 0 to 60 m after start of CDA challenge by calculating AUC of the TSS via the linear trapezoidal method then dividing by the total duration that the participant took to complete CDA challenge assessments. WM is reported as LS mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 7 to Day 14 of each period | TSS was calculated as the sum of the response for 3 components of nasal congestion, rhinorrhoea and post nasal drip. It was rated on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). TSS score ranges from 0-9 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. For Day 1 to 14 of each study period, participants were asked to keep a diary to record their symptoms whilst at home provided by the clinical unit. Reflective rating represented the symptoms over the proceeding 12 h which was performed once daily in the evening (PM). The PM reflective rating was done approximately 12 h after dosing, but before bedtime. If any of the individual components were missing then the TSS was set to be missing for that participant at that timepoint. |
| Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Day 7 to Day 14 of each period | The individual component of TSS nasal symptoms of nasal congestion, rhinorrhoea (runny nose) and post nasal drip was scored on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). The scores of the individual components of TSS ranges from 0-3 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. For Day 1 to 14 of each study period, participants were asked to keep a diary to record their symptoms whilst at home on a diary card provided by the clinical unit. Reflective rating represented the symptoms over the proceeding 12 h which was performed once daily in the PM. The PM reflective rating was done approximately 12 h after dosing, but before bedtime. |
| Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | Day 1, Day 14 and Day 15 of each period (Day 14, 24 h post- dose was done on Day 15) | The assessment of sneezing was done based on a CDA challenge, for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree C, \<15% relative humidity and 5+/-3 ft/sec air velocity, 1 h post dose on Day 1 and 1 h and 24 h post dose on Day 14 (Day 15). Sneezing was scored on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). The score ranges from 0-3 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. It was used to derive the WM CDA challenge value calculated over the time interval 0 to 60 m after start of CDA challenge and the maximum score. WM is reported as LS mean. |
| Mean Change From Baseline to Day 14 of Acoustic Rhinometry (AR) Following Repeat Dosing of SB-705498 at 2 h and 25 h Post-dose | Baseline (Day 1 pre-dose), Day 14 and Day 15 of each period (Day 14, 25 h post dose on Day 14 was evaluated on Day 15) | Overall AR score was obtained by adding minimal cross-sectional area (MCA) for right and left nostril. MCA1 was captured within the nose at a distance of 0 and 2.2 cm and MCA2 at 2.2 and 5.5 cm. MCA1 and MCA2 were captured simultaneously for each nostril, 3 measurements were obtained from each nostril which resulted in 12 data points. Absolute MCA for all regions in left or right nostril was calculated using the 3 acceptable measurements, calculating average of each of right and left MCA's and also by selecting minimum value from these averages to obtain minimum MCA for left and right nostril. Baseline is defined as the value on Day 1 pre- dose. Change from baseline was calculated by subtracting the baseline (Day 1 pre-dose) values from individual post-randomization values done immediately following CDA challenge. In case of missing baseline or post randomization value, the change from baseline was set to be missing. Adjusted mean is reported as LS mean. |
| Mean Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 on Day 14 | Baseline (Day 1 pre-dose) and Day 14 of each period | The RQLQ is a 28-item, disease-specific quality of life questionnaire that measures the functional (physical, emotional, and social) problems troublesome to adults with allergies. The RQLQ has 28 questions in 7 domains (activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms and emotional). All 28 questions were evaluated by the participant in an assessment diary over 2 weeks of treatment period and was rated on a 7-point severity scale ranging from 0 to 6, where 0=least severe to 6=extremely severe. Overall mean was calculated by summing all 28-item scores and dividing by total number of items in the questionnaire. RQLQ score ranges from 0-6 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Baseline was defined as the value on Day 1 pre- dose. Change from baseline was calculated by subtracting baseline (Day 1 pre-dose) values from individual post-randomization values. Adjusted mean is reported as LS mean. |
| Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | Day 1 and 15 of each period (Day 14, 24 h post- dose was assessed on Day 15) | The assessment of TOSS was done based on a CDA challenge, for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree C, \<15% relative humidity and 5+/-3 ft/sec air velocity, 1 h post dose on Day 1 and 1 h and 24 h post dose on Day 14 (Day 15). TOSS was calculated as the sum of the symptom scores for 3 ocular symptoms of itching/burning eyes, tearing/watering eyes, and redness of eyes. It was rated on a 4-point severity scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate and 3=severe (symptom hard to tolerate, interferes with daily activities/sleeping). TOSS score ranges from 0-9 with 0 representing an absence of symptoms and 9 representing severe symptoms. These values were used to derive the WM (s) of the CDA challenge value and the maximum score. WM is reported as LS mean. |
| Pharmacokinetic Parameter of Area Under the Plasma Concentration-time Curves From Time Zero (Pre- Dose) to 3 h and 24 h (t) on Day 1 and Day 14 (AUC [0-3], AUC [0-t]) | Pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period. | Blood samples for pharmacokinetic assessment were collected at pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period. The area under the plasma concentration-time curves from time zero (pre- dose) to 3 h, AUC (0-3) and the last quantifiable concentration, AUC (0-t) (24 h) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The AUC of non-calculable (NC) due to non-quantifiable concentration measured as below lower limit of quantification (NQ) values were imputed by 0.5 x lowest observed AUC (i.e., AUC \[0-3\]: 0.5 x 6.4; AUC\[0-t\]: 0.5 x 6.3). Coefficient of variation (CVb \[%\]) was calculated as, CVb (%) = SQRT (exp \[SD2-1\]) x 100, where SQRT is the square root, exp is the exponent and SD is the standard deviation of the logarithmically transformed data. Analysis was done on the number of participants with non-missing observations (including imputed NC values). |
| Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | Day 1 of each period | TSS was calculated based on a CDA challenge, done for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree C, \<15% relative humidity and 5+/-3 ft/sec air velocity, 1 h and 24 h post dose on Day 1. TSS was calculated as the sum of the response for 3 components of nasal congestion, rhinorrhoea and post nasal drip. It was rated on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). TSS score ranges from 0-9 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. WM for TSS was calculated over the time interval 0 to 60 m after start of CDA challenge by calculating AUC of the TSS via the linear trapezoidal method then dividing by the total duration that the participant took to complete CDA challenge assessments. WM is reported as LS mean. |
| Pharmacokinetic Parameter of Time to Maximum Observed Plasma Concentration (Tmax) on Day 1 and 14 | Pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period. | Blood samples for pharmacokinetic assessment were collected at pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period. Tmax was determined directly from the raw concentration-time data on Day 1 and Day 14 where, NQs were imputed to zero or missing and lower limit of quantification is 2.5 ng /mL. Analysis was done on the number of participants with non-missing observations (including imputed NC values) |
| Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE | Start of study treatment (Day 1 of first period) up to follow up, for up to 28 days. | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalised ratio \>1.5. AEs were classified as potentially drug-related, based on the investigator's judgement. |
| Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | Day 1 (pre-dose) and Day 14 (pre-dose) | ECGs were obtained on Day 1 (pre-dose) and Day 14 (pre- dose) of each period. Single 12-lead ECGs was obtained at each timepoint during the study using an ECG machine that automatically calculated the heart rate (HR) and measures PR, QRS, QT, and QTc intervals. Participants with abnormal (not clinically significant), abnormal (clinically significant) and no result were presented. |
| Number of Participants With Haematology Abnormalities of Potential Clinical Importance (PCI) at Any Time During Treatment | Day 14 of each period | The PCI values of hematology parameters were obtained by multiplying a fixed factor to the site's upper or lower limit normal ranges for each of the parameter. The factors were white blood cell count (WBC): 0.67 for relative low; 1.82 for relative high, haemoglobin (Hb) relative high: male - 1.03; female - 1.13, haematocrit (relative high): male - 1.02; female - 1.17, platelets: 0.67 for relative low; 1.57 for relative high, neutrophils (relative low): 0.83, lymphocytes (relative low): 0.81. |
| Number of Participants With Clinical Chemistry PCI Abnormalities of Albumin, Calcium, Glucose, Potassium, Sodium and Total Carbon Dioxide (CO2) at Any Time During Treatment | Day 14 of each period | The PCI values of albumin, calcium, glucose, potassium, sodium and total CO2 were obtained by multiplying a fixed factor to the site's upper or lower limit normal ranges for each of the parameter. The factors were albumin (relative low): 0.86, calcium: 0.91 for relative low; 1.06 for relative high, glucose: 0.71 for relative low; 1.41 for relative high, potassium: 0.86 for relative low; 1.10 for relative high, sodium: 0.96 for relative low; 1.03 for relative high and total CO2: 0.86 for relative low; 1. 14 for relative high. |
| Number of Participants With Clinical Chemistry PCI Abnormalities of Creatinine, Blood Urea Nitrogen (BUN), Uric Acid, Cholesterol, Triglycerides, Lactate Dehydrogenase (LDH) and Liver Function Test at Any Time During Treatment | Day 14 of each period | The PCI values of clinical chemistry parameters were creatinine: low- male is \<75 micromoles per litre (mcmol/L); low- female is \<65 mcmol/L; high- male \>110 mcmol/L; high- female \>95 mcmol/L, BUN: high is \>1.5 x ULN millimole per litre (mmol/L), uric acid: low- male is \<180 mcmol/L; low- female is \<120 mcmol/L; high- male \>480 mcmol/L; high- female \>420 mcmol/L, cholesterol: low is \<3.9 mmol/L; high is \>6.5 mmol/L \[if age \<=40, if age \>40- high is \>6.55 mmol/L\], triglycerides: low- \<0.5 mmol/L; high- \>2.0 mmol/L, LDH: \>220 units per lire (U/L). For high alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase is \>=2 x ULN U/L. Total bilirubin high is \>=1.5 x ULN mcmol/L, gamma glutamyltransferase (GGT) high: male- \>60 U/L; female \> 40 U/L. |
| Number of Participants With Vital Sign of Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), HR and Body Temperature of PCI Abnormalities at Any Time During Treatment | Day 1 and Day 14 of each period | The PCI values of vital signs were SBP: \<85 and \>160 millimetres of mercury (mmHg), DBP of \<45 and \>100 mmHg, HR of \<40 and \>110 beats per minute (bpm) and body temperature of \<36 and \>37.5oC. |
| Pharmacokinetic Parameter of Maximum Observed Plasma Concentration (Cmax) on Day 1 and 14 | Pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period. | Blood samples for pharmacokinetic assessment were collected at pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period. The first occurrence of Cmax was determined directly from the raw concentration-time data on Day 1 and Day 14 where, NQs were imputed to zero or missing and lower limit of quantification was 2.5 nanogram per millilitre (ng /mL). Logarithmically transformed data is reported for Cmax. CVb (%) was calculated as, CVb (%) = SQRT (exp \[SD2-1\]) x 100, where SD is the standard deviation of the logarithmically transformed data. Analysis was done on the number of participants with non-missing observations (including imputed NC values). |
| Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | Day 1 of each period | The individual components of TSS was calculated based on a CDA challenge, done for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree C, \<15% relative humidity and 5+/-3 ft/sec air velocity, 1 h and 24 h post dose on Day 1. The individual component of TSS nasal symptoms were nasal congestion, rhinorrhoea (runny nose), and post nasal drip It was rated on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). The score ranges from 0-3 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. WM for TSS was calculated over the time interval 0 to 60 m after start of CDA challenge by calculating AUC of the TSS via the linear trapezoidal method then dividing by the total duration that the participant took to complete CDA challenge assessments. WM is reported as LS mean. |
Countries
Canada
Participant flow
Recruitment details
The study was planned on 40 participants, male or female between 18 and 65 years of age with non-allergic rhinitis (NAR), at a single center of Canada from 7th December 2010 to 18th April 2011.
Participants by arm
| Arm | Count |
|---|---|
| All Treatments Combined The study consisted of 2 treatment periods, each of 14 days (2 weeks). The treatment periods were separated by at least 4 weeks of washout period. Participants were administered intranasal spray of SB-705498 12 milligram (mg) or matching placebo as repeat doses for 14 days once daily in treatment period 1 (TP1), and the converse treatments in TP2 two treatment sequences (active/placebo \[A/P\] or placebo/active \[P/A\]) with respect to the randomization. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1:Intervention Period 1 (14 Days) | Protocol Violation | 1 | 1 |
| Period 3:Intervention Period 2 (14 Days) | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | All Treatments Combined |
|---|---|
| Age, Continuous | 40.6 Years STANDARD_DEVIATION 11.48 |
| Race/Ethnicity, Customized African American/African Heritage | 3 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 1 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 2 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 1 Participants |
| Race/Ethnicity, Customized Mixed Race | 1 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 2 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 29 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 39 |
| other Total, other adverse events | 8 / 38 | 9 / 39 |
| serious Total, serious adverse events | 0 / 38 | 0 / 39 |
Outcome results
Primary
Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo
The individual components of TSS was calculated based on a CDA challenge, done for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree C, \<15% relative humidity and 5+/-3 ft/sec air velocity, 1 h and 24 h post dose on Day 14 (Day 15). The individual component of TSS nasal symptoms were nasal congestion, rhinorrhoea (runny nose), and post nasal drip It was rated on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). The scores of the individual components of TSS ranges from 0-3 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. WM for TSS was calculated over the time interval 0 to 60 m after start of CDA challenge by calculating AUC of the TSS via the linear trapezoidal method then dividing by the total duration that the participant took to complete CDA challenge assessments. WM is reported as LS mean.
Time frame: Day 14 to Day 15 of each period (Day 14, 24 h post- dose was done on Day 15)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 nasal congestion, 1 h | 1.09 Score on scale | Standard Deviation 0.667 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 nasal congestion, 24 h | 1.24 Score on scale | Standard Deviation 0.708 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum nasal congestion, 1 h | 1.46 Score on scale | Standard Deviation 0.836 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum nasal congestion, 24 h | 1.61 Score on scale | Standard Deviation 0.823 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 runny nose, 1 h | 1.24 Score on scale | Standard Deviation 0.6 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 runny nose, 24 h | 1.19 Score on scale | Standard Deviation 0.596 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum runny nose, 1 h | 1.68 Score on scale | Standard Deviation 0.709 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum runny nose, 24 h | 1.76 Score on scale | Standard Deviation 0.634 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 post nasal drip, 1 h | 1.14 Score on scale | Standard Deviation 0.642 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 post nasal drip, 24 h | 1.07 Score on scale | Standard Deviation 0.637 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum post nasal drip, 1 h | 1.51 Score on scale | Standard Deviation 0.692 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum post nasal drip, 24 h | 1.45 Score on scale | Standard Deviation 0.724 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum post nasal drip, 1 h | 1.44 Score on scale | Standard Deviation 0.882 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 nasal congestion, 1 h | 1.08 Score on scale | Standard Deviation 0.744 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum runny nose, 1 h | 1.77 Score on scale | Standard Deviation 0.583 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 nasal congestion, 24 h | 1.18 Score on scale | Standard Deviation 0.691 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 post nasal drip, 24 h | 1.10 Score on scale | Standard Deviation 0.803 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum nasal congestion, 1 h | 1.33 Score on scale | Standard Deviation 0.838 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum runny nose, 24 h | 1.95 Score on scale | Standard Deviation 0.655 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum nasal congestion, 24 h | 1.53 Score on scale | Standard Deviation 0.862 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum post nasal drip, 24 h | 1.47 Score on scale | Standard Deviation 0.862 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 runny nose, 1 h | 1.19 Score on scale | Standard Deviation 0.6 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 post nasal drip, 1 h | 1.06 Score on scale | Standard Deviation 0.721 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 runny nose, 24 h | 1.29 Score on scale | Standard Deviation 0.616 |
Primary
Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) Cold Dry Air (CDA) Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo
TSS was calculated based on a CDA challenge, done for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree Celsius (C), \<15% relative humidity and 5+/-3 feet per second (ft/sec) air velocity, 1 h and 24 h post dose on Day 14 (Day 15). TSS was calculated as the sum of the response for 3 components of nasal congestion, rhinorrhoea and post nasal drip. It was rated on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). TSS score ranges from 0-9 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Weighted mean (WM) for TSS was calculated over the time interval 0 to 60 minute (m) after start of CDA challenge by calculating area under the curve (AUC) of the TSS via the linear trapezoidal method then dividing by the total duration that the participant took to complete CDA challenge assessments. WM is reported as least square (LS) mean.
Time frame: Day 14 to Day 15 of each period (Day 14, 24 h post- dose was done on Day 15)
Population: All Subjects population defined as all participants who received at least one dose of study medication. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) Cold Dry Air (CDA) Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 TSS, 1 h | 3.49 Scores on scale | Standard Error 0.259 |
| Placebo | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) Cold Dry Air (CDA) Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 TSS, 24 h | 3.56 Scores on scale | Standard Error 0.263 |
| Placebo | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) Cold Dry Air (CDA) Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum TSS, 1 h | 4.55 Scores on scale | Standard Error 0.285 |
| Placebo | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) Cold Dry Air (CDA) Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum TSS, 24 h | 4.71 Scores on scale | Standard Error 0.295 |
| SB-705498 12 mg | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) Cold Dry Air (CDA) Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum TSS, 24 h | 4.82 Scores on scale | Standard Error 0.295 |
| SB-705498 12 mg | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) Cold Dry Air (CDA) Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 TSS, 1 h | 3.37 Scores on scale | Standard Error 0.254 |
| SB-705498 12 mg | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) Cold Dry Air (CDA) Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | Maximum TSS, 1 h | 4.51 Scores on scale | Standard Error 0.279 |
| SB-705498 12 mg | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) Cold Dry Air (CDA) Challenge, 1 h and 24 h on Day 14 to Compare the Effect of 14 Day Repeat Dosing of Intranasal SB-705498 12 mg With Placebo | WM 0-60 TSS, 24 h | 3.59 Scores on scale | Standard Error 0.262 |
Comparison: Placebo vs SB-705498 12 mg for 1 h in WM 0-60 TSS95% CI: [-0.6, 0.36]
Comparison: Placebo vs SB-705498 12 mg for 24 h in WM 0-60 TSS95% CI: [-0.45, 0.51]
Comparison: Placebo vs SB-705498 12 mg for 1 h in Maximum TSS95% CI: [-0.58, 0.51]
Comparison: Placebo vs SB-705498 12 mg for 24 h in Maximum TSS95% CI: [-0.51, 0.72]
Secondary
Mean Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 on Day 14
The RQLQ is a 28-item, disease-specific quality of life questionnaire that measures the functional (physical, emotional, and social) problems troublesome to adults with allergies. The RQLQ has 28 questions in 7 domains (activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms and emotional). All 28 questions were evaluated by the participant in an assessment diary over 2 weeks of treatment period and was rated on a 7-point severity scale ranging from 0 to 6, where 0=least severe to 6=extremely severe. Overall mean was calculated by summing all 28-item scores and dividing by total number of items in the questionnaire. RQLQ score ranges from 0-6 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. Baseline was defined as the value on Day 1 pre- dose. Change from baseline was calculated by subtracting baseline (Day 1 pre-dose) values from individual post-randomization values. Adjusted mean is reported as LS mean.
Time frame: Baseline (Day 1 pre-dose) and Day 14 of each period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 on Day 14 | -0.15 Scores on scale | Standard Error 0.126 |
| SB-705498 12 mg | Mean Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 on Day 14 | -0.20 Scores on scale | Standard Error 0.126 |
Comparison: Placebo vs SB-705498 12 mg for Day 14 in AR95% CI: [-0.36, 0.26]
Secondary
Mean Change From Baseline to Day 14 of Acoustic Rhinometry (AR) Following Repeat Dosing of SB-705498 at 2 h and 25 h Post-dose
Overall AR score was obtained by adding minimal cross-sectional area (MCA) for right and left nostril. MCA1 was captured within the nose at a distance of 0 and 2.2 cm and MCA2 at 2.2 and 5.5 cm. MCA1 and MCA2 were captured simultaneously for each nostril, 3 measurements were obtained from each nostril which resulted in 12 data points. Absolute MCA for all regions in left or right nostril was calculated using the 3 acceptable measurements, calculating average of each of right and left MCA's and also by selecting minimum value from these averages to obtain minimum MCA for left and right nostril. Baseline is defined as the value on Day 1 pre- dose. Change from baseline was calculated by subtracting the baseline (Day 1 pre-dose) values from individual post-randomization values done immediately following CDA challenge. In case of missing baseline or post randomization value, the change from baseline was set to be missing. Adjusted mean is reported as LS mean.
Time frame: Baseline (Day 1 pre-dose), Day 14 and Day 15 of each period (Day 14, 25 h post dose on Day 14 was evaluated on Day 15)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline to Day 14 of Acoustic Rhinometry (AR) Following Repeat Dosing of SB-705498 at 2 h and 25 h Post-dose | Day 14, 2 h | 0.09 Centimetre square (cm^2) | Standard Error 0.021 |
| Placebo | Mean Change From Baseline to Day 14 of Acoustic Rhinometry (AR) Following Repeat Dosing of SB-705498 at 2 h and 25 h Post-dose | Day 1, 2 h | 0.01 Centimetre square (cm^2) | Standard Error 0.021 |
| Placebo | Mean Change From Baseline to Day 14 of Acoustic Rhinometry (AR) Following Repeat Dosing of SB-705498 at 2 h and 25 h Post-dose | Day 14, 25 h | 0.03 Centimetre square (cm^2) | Standard Error 0.022 |
| SB-705498 12 mg | Mean Change From Baseline to Day 14 of Acoustic Rhinometry (AR) Following Repeat Dosing of SB-705498 at 2 h and 25 h Post-dose | Day 1, 2 h | 0.03 Centimetre square (cm^2) | Standard Error 0.02 |
| SB-705498 12 mg | Mean Change From Baseline to Day 14 of Acoustic Rhinometry (AR) Following Repeat Dosing of SB-705498 at 2 h and 25 h Post-dose | Day 14, 2 h | 0.02 Centimetre square (cm^2) | Standard Error 0.021 |
| SB-705498 12 mg | Mean Change From Baseline to Day 14 of Acoustic Rhinometry (AR) Following Repeat Dosing of SB-705498 at 2 h and 25 h Post-dose | Day 14, 25 h | 0.05 Centimetre square (cm^2) | Standard Error 0.022 |
Comparison: Placebo vs SB-705498 12 mg for Day 1, 2 h in AR95% CI: [-0.03, 0.07]
Comparison: Placebo vs SB-705498 12 mg for Day 14, 2 h in AR95% CI: [-0.13, -0.02]
Comparison: Placebo vs SB-705498 12 mg for Day 14, 25 h in AR95% CI: [-0.04, 0.08]
Secondary
Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo
The individual components of TSS was calculated based on a CDA challenge, done for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree C, \<15% relative humidity and 5+/-3 ft/sec air velocity, 1 h and 24 h post dose on Day 1. The individual component of TSS nasal symptoms were nasal congestion, rhinorrhoea (runny nose), and post nasal drip It was rated on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). The score ranges from 0-3 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. WM for TSS was calculated over the time interval 0 to 60 m after start of CDA challenge by calculating AUC of the TSS via the linear trapezoidal method then dividing by the total duration that the participant took to complete CDA challenge assessments. WM is reported as LS mean.
Time frame: Day 1 of each period
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | WM 0-60 nasal congestion | 1.09 Scores on scale | Standard Deviation 0.687 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | Maximum nasal congestion | 1.47 Scores on scale | Standard Deviation 0.83 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | WM 0-60 runny nose | 1.21 Scores on scale | Standard Deviation 0.609 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | Maximum runny nose | 1.89 Scores on scale | Standard Deviation 0.689 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | WM 0-60 post nasal drip | 1.11 Scores on scale | Standard Deviation 0.665 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | Maximum post nasal drip | 1.53 Scores on scale | Standard Deviation 0.797 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | WM 0-60 post nasal drip | 1.10 Scores on scale | Standard Deviation 0.583 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | WM 0-60 nasal congestion | 1.10 Scores on scale | Standard Deviation 0.562 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | Maximum runny nose | 1.91 Scores on scale | Standard Deviation 0.427 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | Maximum nasal congestion | 1.51 Scores on scale | Standard Deviation 0.756 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | Maximum post nasal drip | 1.55 Scores on scale | Standard Deviation 0.677 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip Elicited by a 1 h CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | WM 0-60 runny nose | 1.34 Scores on scale | Standard Deviation 0.451 |
Secondary
Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498
The individual component of TSS nasal symptoms of nasal congestion, rhinorrhoea (runny nose) and post nasal drip was scored on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). The scores of the individual components of TSS ranges from 0-3 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. For Day 1 to 14 of each study period, participants were asked to keep a diary to record their symptoms whilst at home on a diary card provided by the clinical unit. Reflective rating represented the symptoms over the proceeding 12 h which was performed once daily in the PM. The PM reflective rating was done approximately 12 h after dosing, but before bedtime.
Time frame: Day 7 to Day 14 of each period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 1 | 0.3 Scores on scale | Standard Deviation 0.52 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 13, | 1.1 Scores on scale | Standard Deviation 0.89 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 12 | 1.2 Scores on scale | Standard Deviation 0.75 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 14, | 0.6 Scores on scale | Standard Deviation 0.73 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 7 | 1.1 Scores on scale | Standard Deviation 0.83 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 1 | 0.5 Scores on scale | Standard Deviation 0.65 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 9 | 0.9 Scores on scale | Standard Deviation 0.61 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 7 | 0.9 Scores on scale | Standard Deviation 0.82 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 8 | 1.1 Scores on scale | Standard Deviation 0.76 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 8 | 0.8 Scores on scale | Standard Deviation 0.77 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 13 | 1.2 Scores on scale | Standard Deviation 0.75 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 9 | 0.9 Scores on scale | Standard Deviation 0.76 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 9 | 1.1 Scores on scale | Standard Deviation 0.7 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 10 | 0.9 Scores on scale | Standard Deviation 0.75 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 11 | 1.1 Scores on scale | Standard Deviation 0.81 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 11 | 0.9 Scores on scale | Standard Deviation 0.83 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 10, | 1.1 Scores on scale | Standard Deviation 0.78 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 12 | 1.1 Scores on scale | Standard Deviation 0.91 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 14 | 0.8 Scores on scale | Standard Deviation 0.9 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 13 | 1.0 Scores on scale | Standard Deviation 0.84 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 11, | 1.1 Scores on scale | Standard Deviation 0.91 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 14 | 0.6 Scores on scale | Standard Deviation 0.73 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 10 | 1.1 Scores on scale | Standard Deviation 0.73 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 1 | 0.6 Scores on scale | Standard Deviation 0.72 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 12, | 1.2 Scores on scale | Standard Deviation 0.83 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 7 | 1.2 Scores on scale | Standard Deviation 0.79 |
| Placebo | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 8 | 1.1 Scores on scale | Standard Deviation 0.84 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 7 | 1.2 Scores on scale | Standard Deviation 0.78 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 8 | 1.2 Scores on scale | Standard Deviation 0.78 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 9 | 1.2 Scores on scale | Standard Deviation 0.78 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 10 | 1.2 Scores on scale | Standard Deviation 0.88 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 11 | 1.1 Scores on scale | Standard Deviation 0.87 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 12 | 1.2 Scores on scale | Standard Deviation 0.75 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 13 | 1.1 Scores on scale | Standard Deviation 0.81 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 14 | 0.8 Scores on scale | Standard Deviation 0.82 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 1 | 0.3 Scores on scale | Standard Deviation 0.5 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 7 | 1.2 Scores on scale | Standard Deviation 0.8 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 8 | 1.1 Scores on scale | Standard Deviation 0.8 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 9 | 1.2 Scores on scale | Standard Deviation 0.84 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 10, | 1.1 Scores on scale | Standard Deviation 0.75 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 11, | 1.1 Scores on scale | Standard Deviation 0.78 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 12, | 1.0 Scores on scale | Standard Deviation 0.77 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 13, | 1.1 Scores on scale | Standard Deviation 0.85 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Runny nose, Day 14, | 0.3 Scores on scale | Standard Deviation 0.62 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 1 | 0.4 Scores on scale | Standard Deviation 0.6 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 7 | 1.0 Scores on scale | Standard Deviation 0.84 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 8 | 1.0 Scores on scale | Standard Deviation 0.83 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 9 | 1.1 Scores on scale | Standard Deviation 0.92 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 10 | 0.9 Scores on scale | Standard Deviation 0.83 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 11 | 0.8 Scores on scale | Standard Deviation 0.82 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 12 | 0.8 Scores on scale | Standard Deviation 0.78 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 13 | 0.8 Scores on scale | Standard Deviation 0.81 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Post nasal drip, Day 14 | 0.7 Scores on scale | Standard Deviation 0.77 |
| SB-705498 12 mg | Mean Individual Component of TSS of Rhinorrhoea (Runny Nose), Nasal Congestion and Post-nasal Drip From Day 7 to Day 14 Following Repeat Doses of SB-705498 | Nasal congestion, Day 1 | 0.5 Scores on scale | Standard Deviation 0.6 |
Secondary
Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo
The assessment of sneezing was done based on a CDA challenge, for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree C, \<15% relative humidity and 5+/-3 ft/sec air velocity, 1 h post dose on Day 1 and 1 h and 24 h post dose on Day 14 (Day 15). Sneezing was scored on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). The score ranges from 0-3 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. It was used to derive the WM CDA challenge value calculated over the time interval 0 to 60 m after start of CDA challenge and the maximum score. WM is reported as LS mean.
Time frame: Day 1, Day 14 and Day 15 of each period (Day 14, 24 h post- dose was done on Day 15)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | WM 0-60, Day 14, 1 h | 0.23 Scores on scale | Standard Error 0.085 |
| Placebo | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | Maximum, Day 1, 1 h | 0.50 Scores on scale | Standard Error 0.131 |
| Placebo | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | WM 0-60, Day 1, 1 h | 0.28 Scores on scale | Standard Error 0.09 |
| Placebo | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | Maximum, Day 14, 1 h | 0.35 Scores on scale | Standard Error 0.123 |
| Placebo | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | Maximum, Day 14, 24 h | 0.45 Scores on scale | Standard Error 0.111 |
| Placebo | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | WM 0-60, Day 14, 24 h | 0.28 Scores on scale | Standard Error 0.083 |
| SB-705498 12 mg | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | Maximum, Day 14, 24 h | 0.43 Scores on scale | Standard Error 0.111 |
| SB-705498 12 mg | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | WM 0-60, Day 1, 1 h | 0.25 Scores on scale | Standard Error 0.09 |
| SB-705498 12 mg | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | WM 0-60, Day 14, 1 h | 0.21 Scores on scale | Standard Error 0.084 |
| SB-705498 12 mg | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | WM 0-60, Day 14, 24 h | 0.23 Scores on scale | Standard Error 0.083 |
| SB-705498 12 mg | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | Maximum, Day 1, 1 h | 0.43 Scores on scale | Standard Error 0.13 |
| SB-705498 12 mg | Mean Sneezing Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg With Placebo | Maximum, Day 14, 1 h | 0.34 Scores on scale | Standard Error 0.122 |
Comparison: Placebo vs SB-705498 12 mg for Day 1, 1 h in WM 0-60 sneezing95% CI: [-0.14, 0.08]
Comparison: Placebo vs SB-705498 12 mg for Day 14, 1 h in WM 0-60 sneezing95% CI: [-0.13, 0.09]
Comparison: Placebo vs SB-705498 12 mg for Day 14, 24 h in WM 0-60 sneezing95% CI: [-0.2, 0.11]
Comparison: Placebo vs SB-705498 12 mg for Day 1, 1 h in Maximum sneezing95% CI: [-0.28, 0.14]
Comparison: Placebo vs SB-705498 12 mg for Day 14, 1 h in Maximum sneezing95% CI: [-0.15, 0.13]
Comparison: Placebo vs SB-705498 12 mg for Day 1, 24 h in Maximum sneezing95% CI: [-0.2, 0.16]
Secondary
Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo
The assessment of TOSS was done based on a CDA challenge, for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree C, \<15% relative humidity and 5+/-3 ft/sec air velocity, 1 h post dose on Day 1 and 1 h and 24 h post dose on Day 14 (Day 15). TOSS was calculated as the sum of the symptom scores for 3 ocular symptoms of itching/burning eyes, tearing/watering eyes, and redness of eyes. It was rated on a 4-point severity scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate and 3=severe (symptom hard to tolerate, interferes with daily activities/sleeping). TOSS score ranges from 0-9 with 0 representing an absence of symptoms and 9 representing severe symptoms. These values were used to derive the WM (s) of the CDA challenge value and the maximum score. WM is reported as LS mean.
Time frame: Day 1 and 15 of each period (Day 14, 24 h post- dose was assessed on Day 15)
Population: All Subjects Population. Only those participants available at the specified time points was analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | WM 0-60 TOSS, Day 1 | 1.99 Scores on scale | Standard Error 0.273 |
| Placebo | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | WM 0-60 TOSS, Day 14, 1 h | 2.05 Scores on scale | Standard Error 0.276 |
| Placebo | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | WM 0-60 TOSS, Day 14, 24 h | 1.91 Scores on scale | Standard Error 0.261 |
| Placebo | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | Maximum TOSS, Day 1, 1 h | 3.08 Scores on scale | Standard Error 0.366 |
| Placebo | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | Maximum TOSS, Day 14, 1 h | 2.81 Scores on scale | Standard Error 0.35 |
| Placebo | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | Maximum TOSS, Day 14, 24 h | 2.86 Scores on scale | Standard Error 0.355 |
| SB-705498 12 mg | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | Maximum TOSS, Day 14, 1 h | 3.07 Scores on scale | Standard Error 0.344 |
| SB-705498 12 mg | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | WM 0-60 TOSS, Day 1 | 2.26 Scores on scale | Standard Error 0.272 |
| SB-705498 12 mg | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | Maximum TOSS, Day 1, 1 h | 3.27 Scores on scale | Standard Error 0.364 |
| SB-705498 12 mg | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | WM 0-60 TOSS, Day 14, 1 h | 2.16 Scores on scale | Standard Error 0.272 |
| SB-705498 12 mg | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | Maximum TOSS, Day 14, 24 h | 3.15 Scores on scale | Standard Error 0.354 |
| SB-705498 12 mg | Mean Total Ocular Symptom Score (TOSS; Red, Itchy and Tearing Eyes) Elicited by a 1 h CDA Challenge at 1 h Post-dose on Day 1, 1 and 24 h Post-dose on Day 14 to Compare the Effect of Intranasal SB-705498 12 mg Compared With Placebo | WM 0-60 TOSS, Day 14, 24 h | 2.12 Scores on scale | Standard Error 0.261 |
Comparison: Placebo vs SB-705498 12 mg for Day 1, 1 h in Maximum TOSS95% CI: [-0.3, 0.68]
Comparison: Placebo vs SB-705498 12 mg for Day 1, 1 h in WM 0-60 TOSS95% CI: [-0.06, 0.6]
Comparison: Placebo vs SB-705498 12 mg for Day 14, 1 h in WM 0-60 TOSS95% CI: [-0.32, 0.53]
Comparison: Placebo vs SB-705498 12 mg for Day 14, 24 h in WM 0-60 TOSS95% CI: [-0.22, 0.63]
Comparison: Placebo vs SB-705498 12 mg for Day 14, 1 h in Maximum TOSS95% CI: [-0.34, 0.86]
Comparison: Placebo vs SB-705498 12 mg for Day 14, 24 h in Maximum TOSS95% CI: [-0.15, 0.73]
Secondary
Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo
TSS was calculated based on a CDA challenge, done for 1 h in a controlled environmental exposure chamber which was validated for 14+/-5 degree C, \<15% relative humidity and 5+/-3 ft/sec air velocity, 1 h and 24 h post dose on Day 1. TSS was calculated as the sum of the response for 3 components of nasal congestion, rhinorrhoea and post nasal drip. It was rated on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). TSS score ranges from 0-9 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. WM for TSS was calculated over the time interval 0 to 60 m after start of CDA challenge by calculating AUC of the TSS via the linear trapezoidal method then dividing by the total duration that the participant took to complete CDA challenge assessments. WM is reported as LS mean.
Time frame: Day 1 of each period
Population: All Subjects Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | WM 0-60 TSS | 3.44 Scores on scale | Standard Error 0.229 |
| Placebo | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | Maximum TSS | 4.80 Scores on scale | Standard Error 0.252 |
| SB-705498 12 mg | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | WM 0-60 TSS | 3.56 Scores on scale | Standard Error 0.227 |
| SB-705498 12 mg | Mean Total Symptom Score (TSS) Elicited by a 1 Hour (h) CDA Challenge, 1 h Post-dose on Day 1 to Compare the Effect of a Single Dose of 12 mg Intranasal SB-705498 With Placebo | Maximum TSS | 4.89 Scores on scale | Standard Error 0.249 |
Comparison: Placebo vs SB-705498 12 mg for WM 0-60 TSS95% CI: [-0.3, 0.54]
Comparison: Placebo vs SB-705498 12 mg for Maximum TSS95% CI: [-0.39, 0.57]
Secondary
Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498
TSS was calculated as the sum of the response for 3 components of nasal congestion, rhinorrhoea and post nasal drip. It was rated on a 4-point scale ranging from 0 to 3, where: 0=absent, 1=mild, 2=moderate, and 3=severe (symptom hard to tolerate). TSS score ranges from 0-9 with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms. For Day 1 to 14 of each study period, participants were asked to keep a diary to record their symptoms whilst at home provided by the clinical unit. Reflective rating represented the symptoms over the proceeding 12 h which was performed once daily in the evening (PM). The PM reflective rating was done approximately 12 h after dosing, but before bedtime. If any of the individual components were missing then the TSS was set to be missing for that participant at that timepoint.
Time frame: Day 7 to Day 14 of each period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 7 | 3.3 Scores on scale | Standard Deviation 1.86 |
| Placebo | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 11 | 3.1 Scores on scale | Standard Deviation 2.14 |
| Placebo | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 9 | 2.9 Scores on scale | Standard Deviation 1.5 |
| Placebo | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 12 | 3.6 Scores on scale | Standard Deviation 2.02 |
| Placebo | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 8 | 3.1 Scores on scale | Standard Deviation 1.87 |
| Placebo | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 13 | 3.3 Scores on scale | Standard Deviation 2.01 |
| Placebo | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 10 | 3.1 Scores on scale | Standard Deviation 1.87 |
| Placebo | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 14 | 2.0 Scores on scale | Standard Deviation 1.88 |
| Placebo | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 1 | 1.4 Scores on scale | Standard Deviation 1.53 |
| SB-705498 12 mg | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 14 | 1.8 Scores on scale | Standard Deviation 1.82 |
| SB-705498 12 mg | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 1 | 1.2 Scores on scale | Standard Deviation 1.29 |
| SB-705498 12 mg | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 7 | 3.4 Scores on scale | Standard Deviation 1.83 |
| SB-705498 12 mg | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 8 | 3.3 Scores on scale | Standard Deviation 1.99 |
| SB-705498 12 mg | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 9 | 3.5 Scores on scale | Standard Deviation 2.01 |
| SB-705498 12 mg | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 10 | 3.2 Scores on scale | Standard Deviation 1.93 |
| SB-705498 12 mg | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 11 | 3.0 Scores on scale | Standard Deviation 2.01 |
| SB-705498 12 mg | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 12 | 2.9 Scores on scale | Standard Deviation 1.83 |
| SB-705498 12 mg | Mean TSS From Day 7 to Day 14 (Post-dose Prior to Challenge) Following Repeat Doses of SB-705498 | Day 13 | 2.9 Scores on scale | Standard Deviation 1.97 |
Secondary
Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings
ECGs were obtained on Day 1 (pre-dose) and Day 14 (pre- dose) of each period. Single 12-lead ECGs was obtained at each timepoint during the study using an ECG machine that automatically calculated the heart rate (HR) and measures PR, QRS, QT, and QTc intervals. Participants with abnormal (not clinically significant), abnormal (clinically significant) and no result were presented.
Time frame: Day 1 (pre-dose) and Day 14 (pre-dose)
Population: All Subjects Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | Abnormal - Not clinically significant, Day 1 | 6 Participants |
| Placebo | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | Abnormal - Not clinically significant, Day 14 | 2 Participants |
| Placebo | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | Abnormal - Clinically significant, Day 1 | 0 Participants |
| Placebo | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | Abnormal - Clinically significant, Day 14 | 0 Participants |
| Placebo | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | No result, Day 1 | 2 Participants |
| Placebo | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | No result, Day 14 | 1 Participants |
| SB-705498 12 mg | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | No result, Day 1 | 2 Participants |
| SB-705498 12 mg | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | Abnormal - Not clinically significant, Day 1 | 3 Participants |
| SB-705498 12 mg | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | Abnormal - Clinically significant, Day 14 | 0 Participants |
| SB-705498 12 mg | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | Abnormal - Not clinically significant, Day 14 | 2 Participants |
| SB-705498 12 mg | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | No result, Day 14 | 0 Participants |
| SB-705498 12 mg | Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings | Abnormal - Clinically significant, Day 1 | 0 Participants |
Secondary
Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalised ratio \>1.5. AEs were classified as potentially drug-related, based on the investigator's judgement.
Time frame: Start of study treatment (Day 1 of first period) up to follow up, for up to 28 days.
Population: All Subjects Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE | Any AE | 8 Participants |
| Placebo | Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE | Any SAE | 0 Participants |
| Placebo | Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE | Drug- related AE | 2 Participants |
| SB-705498 12 mg | Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE | Any AE | 9 Participants |
| SB-705498 12 mg | Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE | Any SAE | 0 Participants |
| SB-705498 12 mg | Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE | Drug- related AE | 1 Participants |
Secondary
Number of Participants With Clinical Chemistry PCI Abnormalities of Albumin, Calcium, Glucose, Potassium, Sodium and Total Carbon Dioxide (CO2) at Any Time During Treatment
The PCI values of albumin, calcium, glucose, potassium, sodium and total CO2 were obtained by multiplying a fixed factor to the site's upper or lower limit normal ranges for each of the parameter. The factors were albumin (relative low): 0.86, calcium: 0.91 for relative low; 1.06 for relative high, glucose: 0.71 for relative low; 1.41 for relative high, potassium: 0.86 for relative low; 1.10 for relative high, sodium: 0.96 for relative low; 1.03 for relative high and total CO2: 0.86 for relative low; 1. 14 for relative high.
Time frame: Day 14 of each period
Population: All Subjects Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinical Chemistry PCI Abnormalities of Albumin, Calcium, Glucose, Potassium, Sodium and Total Carbon Dioxide (CO2) at Any Time During Treatment | 0 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Chemistry PCI Abnormalities of Albumin, Calcium, Glucose, Potassium, Sodium and Total Carbon Dioxide (CO2) at Any Time During Treatment | 1 Participants |
Secondary
Number of Participants With Clinical Chemistry PCI Abnormalities of Creatinine, Blood Urea Nitrogen (BUN), Uric Acid, Cholesterol, Triglycerides, Lactate Dehydrogenase (LDH) and Liver Function Test at Any Time During Treatment
The PCI values of clinical chemistry parameters were creatinine: low- male is \<75 micromoles per litre (mcmol/L); low- female is \<65 mcmol/L; high- male \>110 mcmol/L; high- female \>95 mcmol/L, BUN: high is \>1.5 x ULN millimole per litre (mmol/L), uric acid: low- male is \<180 mcmol/L; low- female is \<120 mcmol/L; high- male \>480 mcmol/L; high- female \>420 mcmol/L, cholesterol: low is \<3.9 mmol/L; high is \>6.5 mmol/L \[if age \<=40, if age \>40- high is \>6.55 mmol/L\], triglycerides: low- \<0.5 mmol/L; high- \>2.0 mmol/L, LDH: \>220 units per lire (U/L). For high alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase is \>=2 x ULN U/L. Total bilirubin high is \>=1.5 x ULN mcmol/L, gamma glutamyltransferase (GGT) high: male- \>60 U/L; female \> 40 U/L.
Time frame: Day 14 of each period
Population: All Subjects Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Clinical Chemistry PCI Abnormalities of Creatinine, Blood Urea Nitrogen (BUN), Uric Acid, Cholesterol, Triglycerides, Lactate Dehydrogenase (LDH) and Liver Function Test at Any Time During Treatment | Creatinine, High | 1 Participants |
| Placebo | Number of Participants With Clinical Chemistry PCI Abnormalities of Creatinine, Blood Urea Nitrogen (BUN), Uric Acid, Cholesterol, Triglycerides, Lactate Dehydrogenase (LDH) and Liver Function Test at Any Time During Treatment | Uric acid, High | 1 Participants |
| Placebo | Number of Participants With Clinical Chemistry PCI Abnormalities of Creatinine, Blood Urea Nitrogen (BUN), Uric Acid, Cholesterol, Triglycerides, Lactate Dehydrogenase (LDH) and Liver Function Test at Any Time During Treatment | GGT, High | 2 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Chemistry PCI Abnormalities of Creatinine, Blood Urea Nitrogen (BUN), Uric Acid, Cholesterol, Triglycerides, Lactate Dehydrogenase (LDH) and Liver Function Test at Any Time During Treatment | Creatinine, High | 0 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Chemistry PCI Abnormalities of Creatinine, Blood Urea Nitrogen (BUN), Uric Acid, Cholesterol, Triglycerides, Lactate Dehydrogenase (LDH) and Liver Function Test at Any Time During Treatment | Uric acid, High | 0 Participants |
| SB-705498 12 mg | Number of Participants With Clinical Chemistry PCI Abnormalities of Creatinine, Blood Urea Nitrogen (BUN), Uric Acid, Cholesterol, Triglycerides, Lactate Dehydrogenase (LDH) and Liver Function Test at Any Time During Treatment | GGT, High | 2 Participants |
Secondary
Number of Participants With Haematology Abnormalities of Potential Clinical Importance (PCI) at Any Time During Treatment
The PCI values of hematology parameters were obtained by multiplying a fixed factor to the site's upper or lower limit normal ranges for each of the parameter. The factors were white blood cell count (WBC): 0.67 for relative low; 1.82 for relative high, haemoglobin (Hb) relative high: male - 1.03; female - 1.13, haematocrit (relative high): male - 1.02; female - 1.17, platelets: 0.67 for relative low; 1.57 for relative high, neutrophils (relative low): 0.83, lymphocytes (relative low): 0.81.
Time frame: Day 14 of each period
Population: All Subjects Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Haematology Abnormalities of Potential Clinical Importance (PCI) at Any Time During Treatment | Total neutrophils, PCI- Low | 1 Participants |
| Placebo | Number of Participants With Haematology Abnormalities of Potential Clinical Importance (PCI) at Any Time During Treatment | Lymphocytes, PCI- Low | 0 Participants |
| SB-705498 12 mg | Number of Participants With Haematology Abnormalities of Potential Clinical Importance (PCI) at Any Time During Treatment | Lymphocytes, PCI- Low | 2 Participants |
| SB-705498 12 mg | Number of Participants With Haematology Abnormalities of Potential Clinical Importance (PCI) at Any Time During Treatment | Total neutrophils, PCI- Low | 2 Participants |
Secondary
Number of Participants With Vital Sign of Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), HR and Body Temperature of PCI Abnormalities at Any Time During Treatment
The PCI values of vital signs were SBP: \<85 and \>160 millimetres of mercury (mmHg), DBP of \<45 and \>100 mmHg, HR of \<40 and \>110 beats per minute (bpm) and body temperature of \<36 and \>37.5oC.
Time frame: Day 1 and Day 14 of each period
Population: All Subjects Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Sign of Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), HR and Body Temperature of PCI Abnormalities at Any Time During Treatment | SBP, Low | 0 Participants |
| Placebo | Number of Participants With Vital Sign of Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), HR and Body Temperature of PCI Abnormalities at Any Time During Treatment | HR, High | 1 Participants |
| Placebo | Number of Participants With Vital Sign of Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), HR and Body Temperature of PCI Abnormalities at Any Time During Treatment | Body temperature, Low | 7 Participants |
| SB-705498 12 mg | Number of Participants With Vital Sign of Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), HR and Body Temperature of PCI Abnormalities at Any Time During Treatment | Body temperature, Low | 14 Participants |
| SB-705498 12 mg | Number of Participants With Vital Sign of Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), HR and Body Temperature of PCI Abnormalities at Any Time During Treatment | SBP, Low | 1 Participants |
| SB-705498 12 mg | Number of Participants With Vital Sign of Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), HR and Body Temperature of PCI Abnormalities at Any Time During Treatment | HR, High | 2 Participants |
Secondary
Pharmacokinetic Parameter of Area Under the Plasma Concentration-time Curves From Time Zero (Pre- Dose) to 3 h and 24 h (t) on Day 1 and Day 14 (AUC [0-3], AUC [0-t])
Blood samples for pharmacokinetic assessment were collected at pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period. The area under the plasma concentration-time curves from time zero (pre- dose) to 3 h, AUC (0-3) and the last quantifiable concentration, AUC (0-t) (24 h) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The AUC of non-calculable (NC) due to non-quantifiable concentration measured as below lower limit of quantification (NQ) values were imputed by 0.5 x lowest observed AUC (i.e., AUC \[0-3\]: 0.5 x 6.4; AUC\[0-t\]: 0.5 x 6.3). Coefficient of variation (CVb \[%\]) was calculated as, CVb (%) = SQRT (exp \[SD2-1\]) x 100, where SQRT is the square root, exp is the exponent and SD is the standard deviation of the logarithmically transformed data. Analysis was done on the number of participants with non-missing observations (including imputed NC values).
Time frame: Pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period.
Population: Analysis was done on Pharmacokinetic Population, defined as participants in the 'All Subjects' population for whom a pharmacokinetic sample was obtained and analysed. Imputed NC values were derived for AUC (0-3), on Day 1 for 3 participants and for AUC (0-t) on Day 1 for 2 participants.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetic Parameter of Area Under the Plasma Concentration-time Curves From Time Zero (Pre- Dose) to 3 h and 24 h (t) on Day 1 and Day 14 (AUC [0-3], AUC [0-t]) | AUC (0-3), Day 1 | 64.01 Nanogram × hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 197.5 |
| Placebo | Pharmacokinetic Parameter of Area Under the Plasma Concentration-time Curves From Time Zero (Pre- Dose) to 3 h and 24 h (t) on Day 1 and Day 14 (AUC [0-3], AUC [0-t]) | AUC (0-3), Day 14 | 144.46 Nanogram × hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 107.7 |
| Placebo | Pharmacokinetic Parameter of Area Under the Plasma Concentration-time Curves From Time Zero (Pre- Dose) to 3 h and 24 h (t) on Day 1 and Day 14 (AUC [0-3], AUC [0-t]) | AUC (0-t), Day 1 | 65.08 Nanogram × hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 186.5 |
| Placebo | Pharmacokinetic Parameter of Area Under the Plasma Concentration-time Curves From Time Zero (Pre- Dose) to 3 h and 24 h (t) on Day 1 and Day 14 (AUC [0-3], AUC [0-t]) | AUC (0-t), Day 14 | 950.47 Nanogram × hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 125.1 |
Secondary
Pharmacokinetic Parameter of Maximum Observed Plasma Concentration (Cmax) on Day 1 and 14
Blood samples for pharmacokinetic assessment were collected at pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period. The first occurrence of Cmax was determined directly from the raw concentration-time data on Day 1 and Day 14 where, NQs were imputed to zero or missing and lower limit of quantification was 2.5 nanogram per millilitre (ng /mL). Logarithmically transformed data is reported for Cmax. CVb (%) was calculated as, CVb (%) = SQRT (exp \[SD2-1\]) x 100, where SD is the standard deviation of the logarithmically transformed data. Analysis was done on the number of participants with non-missing observations (including imputed NC values).
Time frame: Pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period.
Population: Pharmacokinetic population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetic Parameter of Maximum Observed Plasma Concentration (Cmax) on Day 1 and 14 | Day 1 | 44.040 ng/mL | Geometric Coefficient of Variation 152.3 |
| Placebo | Pharmacokinetic Parameter of Maximum Observed Plasma Concentration (Cmax) on Day 1 and 14 | Day 14 | 72.800 ng/mL | Geometric Coefficient of Variation 111.5 |
Secondary
Pharmacokinetic Parameter of Time to Maximum Observed Plasma Concentration (Tmax) on Day 1 and 14
Blood samples for pharmacokinetic assessment were collected at pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period. Tmax was determined directly from the raw concentration-time data on Day 1 and Day 14 where, NQs were imputed to zero or missing and lower limit of quantification is 2.5 ng /mL. Analysis was done on the number of participants with non-missing observations (including imputed NC values)
Time frame: Pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period.
Population: Pharmacokinetic Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Pharmacokinetic Parameter of Time to Maximum Observed Plasma Concentration (Tmax) on Day 1 and 14 | Day 14 | 2.9833 h |
| Placebo | Pharmacokinetic Parameter of Time to Maximum Observed Plasma Concentration (Tmax) on Day 1 and 14 | Day 1 | 2.0000 h |