Trial Outcomes & Findings for SB705498 Proof of Concept Chamber Challenge in Subjects With Non Allergic Rhinitis (NCT NCT01424514)
NCT ID: NCT01424514
Last Updated: 2018-01-29
Results Overview
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.
COMPLETED
PHASE2
40 participants
Day 14 to Day 15 of each period (Day 14, 24 h post- dose was done on Day 15)
2018-01-29
Participant Flow
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.
Participant milestones
| Measure |
Active Then Placebo
Participants received repeat doses of intranasal spray of SB-705498 12 milligram (mg) as an active intervention once daily for 14 days during intervention period 1 according to a plan of randomization. After a washout period of 4 weeks, participants then received repeat doses of matching placebo once daily for 14 days during intervention period 2.
|
Placebo Then Active
Participants received repeat doses of matching placebo once daily for 14 days during intervention period 1 according to a plan of randomization. After a washout period of 4 weeks, participants then received repeat doses of intranasal spray of SB-705498 12 mg as an active intervention once daily for 14 days during intervention
|
|---|---|---|
|
Period 1:Intervention Period 1 (14 Days)
STARTED
|
20
|
20
|
|
Period 1:Intervention Period 1 (14 Days)
COMPLETED
|
19
|
19
|
|
Period 1:Intervention Period 1 (14 Days)
NOT COMPLETED
|
1
|
1
|
|
Period 2:Washout Period (4 Weeks)
STARTED
|
19
|
19
|
|
Period 2:Washout Period (4 Weeks)
COMPLETED
|
19
|
19
|
|
Period 2:Washout Period (4 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Period 3:Intervention Period 2 (14 Days)
STARTED
|
19
|
19
|
|
Period 3:Intervention Period 2 (14 Days)
COMPLETED
|
18
|
19
|
|
Period 3:Intervention Period 2 (14 Days)
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Active Then Placebo
Participants received repeat doses of intranasal spray of SB-705498 12 milligram (mg) as an active intervention once daily for 14 days during intervention period 1 according to a plan of randomization. After a washout period of 4 weeks, participants then received repeat doses of matching placebo once daily for 14 days during intervention period 2.
|
Placebo Then Active
Participants received repeat doses of matching placebo once daily for 14 days during intervention period 1 according to a plan of randomization. After a washout period of 4 weeks, participants then received repeat doses of intranasal spray of SB-705498 12 mg as an active intervention once daily for 14 days during intervention
|
|---|---|---|
|
Period 1:Intervention Period 1 (14 Days)
Protocol Violation
|
1
|
1
|
|
Period 3:Intervention Period 2 (14 Days)
Protocol Violation
|
1
|
0
|
Baseline Characteristics
SB705498 Proof of Concept Chamber Challenge in Subjects With Non Allergic Rhinitis
Baseline characteristics by cohort
| Measure |
All Treatments Combined
n=40 Participants
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.
|
|---|---|
|
Age, Continuous
|
40.6 Years
STANDARD_DEVIATION 11.48 • n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - Central/South Asian Heritage
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - East Asian Heritage
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - South East Asian Heritage
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - Arabic/North African Heritage
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
29 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Mixed Race
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
3.37 Scores on scale
Standard Error 0.254
|
|
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
|
3.59 Scores on scale
Standard Error 0.262
|
|
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
|
4.51 Scores on scale
Standard Error 0.279
|
|
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
|
4.82 Scores on scale
Standard Error 0.295
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
1.08 Score on scale
Standard Deviation 0.744
|
|
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
|
1.18 Score on scale
Standard Deviation 0.691
|
|
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
|
1.33 Score on scale
Standard Deviation 0.838
|
|
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
|
1.53 Score on scale
Standard Deviation 0.862
|
|
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 0.600
|
1.19 Score on scale
Standard Deviation 0.600
|
|
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
|
1.29 Score on scale
Standard Deviation 0.616
|
|
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
|
1.77 Score on scale
Standard Deviation 0.583
|
|
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
|
1.95 Score on scale
Standard Deviation 0.655
|
|
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
|
1.06 Score on scale
Standard Deviation 0.721
|
|
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
|
1.10 Score on scale
Standard Deviation 0.803
|
|
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
|
1.44 Score on scale
Standard Deviation 0.882
|
|
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
|
1.47 Score on scale
Standard Deviation 0.862
|
SECONDARY outcome
Timeframe: Day 1 of each periodPopulation: All Subjects Population.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=40 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
3.56 Scores on scale
Standard Error 0.227
|
|
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
|
4.89 Scores on scale
Standard Error 0.249
|
SECONDARY outcome
Timeframe: Day 1 of each periodPopulation: All Subjects Population.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
1.10 Scores on scale
Standard Deviation 0.583
|
|
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
|
1.55 Scores on scale
Standard Deviation 0.677
|
|
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
|
1.10 Scores on scale
Standard Deviation 0.562
|
|
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 0.830
|
1.51 Scores on scale
Standard Deviation 0.756
|
|
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
|
1.34 Scores on scale
Standard Deviation 0.451
|
|
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
|
1.91 Scores on scale
Standard Deviation 0.427
|
SECONDARY outcome
Timeframe: Day 7 to Day 14 of each periodPopulation: All Subjects Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
1.2 Scores on scale
Standard Deviation 1.29
|
|
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
|
3.4 Scores on scale
Standard Deviation 1.83
|
|
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
|
3.3 Scores on scale
Standard Deviation 1.99
|
|
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 1.50
|
3.5 Scores on scale
Standard Deviation 2.01
|
|
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
|
3.2 Scores on scale
Standard Deviation 1.93
|
|
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
|
3.0 Scores on scale
Standard Deviation 2.01
|
|
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
|
2.9 Scores on scale
Standard Deviation 1.83
|
|
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
|
2.9 Scores on scale
Standard Deviation 1.97
|
|
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
|
1.8 Scores on scale
Standard Deviation 1.82
|
SECONDARY outcome
Timeframe: Day 7 to Day 14 of each periodPopulation: All Subjects Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
0.5 Scores on scale
Standard Deviation 0.60
|
|
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
|
1.2 Scores on scale
Standard Deviation 0.78
|
|
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
|
1.2 Scores on scale
Standard Deviation 0.78
|
|
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
|
1.2 Scores on scale
Standard Deviation 0.78
|
|
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
|
1.2 Scores on scale
Standard Deviation 0.88
|
|
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
|
1.1 Scores on scale
Standard Deviation 0.87
|
|
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
|
1.2 Scores on scale
Standard Deviation 0.75
|
|
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
|
1.1 Scores on scale
Standard Deviation 0.81
|
|
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 0.90
|
0.8 Scores on scale
Standard Deviation 0.82
|
|
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
|
0.3 Scores on scale
Standard Deviation 0.50
|
|
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
|
1.2 Scores on scale
Standard Deviation 0.80
|
|
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
|
1.1 Scores on scale
Standard Deviation 0.80
|
|
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 0.70
|
1.2 Scores on scale
Standard Deviation 0.84
|
|
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
|
1.1 Scores on scale
Standard Deviation 0.75
|
|
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
|
1.1 Scores on scale
Standard Deviation 0.78
|
|
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
|
1.0 Scores on scale
Standard Deviation 0.77
|
|
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
|
1.1 Scores on scale
Standard Deviation 0.85
|
|
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
|
0.3 Scores on scale
Standard Deviation 0.62
|
|
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
|
0.4 Scores on scale
Standard Deviation 0.60
|
|
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
|
1.0 Scores on scale
Standard Deviation 0.84
|
|
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
|
1.0 Scores on scale
Standard Deviation 0.83
|
|
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
|
1.1 Scores on scale
Standard Deviation 0.92
|
|
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
|
0.9 Scores on scale
Standard Deviation 0.83
|
|
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
|
0.8 Scores on scale
Standard Deviation 0.82
|
|
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
|
0.8 Scores on scale
Standard Deviation 0.78
|
|
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
|
0.8 Scores on scale
Standard Deviation 0.81
|
|
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
|
0.7 Scores on scale
Standard Deviation 0.77
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=40 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
0.43 Scores on scale
Standard Error 0.111
|
|
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 0.090
|
0.25 Scores on scale
Standard Error 0.090
|
|
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
|
0.21 Scores on scale
Standard Error 0.084
|
|
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
|
0.23 Scores on scale
Standard Error 0.083
|
|
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
|
0.43 Scores on scale
Standard Error 0.130
|
|
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
|
0.34 Scores on scale
Standard Error 0.122
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=40 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
0.03 Centimetre square (cm^2)
Standard Error 0.020
|
|
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
|
0.02 Centimetre square (cm^2)
Standard Error 0.021
|
|
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
|
0.05 Centimetre square (cm^2)
Standard Error 0.022
|
SECONDARY outcome
Timeframe: Baseline (Day 1 pre-dose) and Day 14 of each periodPopulation: All Subjects Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=38 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
-0.20 Scores on scale
Standard Error 0.126
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=40 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
2.26 Scores on scale
Standard Error 0.272
|
|
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
|
2.16 Scores on scale
Standard Error 0.272
|
|
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
|
2.12 Scores on scale
Standard Error 0.261
|
|
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
|
3.27 Scores on scale
Standard Error 0.364
|
|
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 0.350
|
3.07 Scores on scale
Standard Error 0.344
|
|
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
|
3.15 Scores on scale
Standard Error 0.354
|
SECONDARY outcome
Timeframe: 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.
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).
Outcome measures
| Measure |
Placebo
n=39 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period.Population: Pharmacokinetic population.
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).
Outcome measures
| Measure |
Placebo
n=39 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
—
|
|
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 outcome
Timeframe: Pre-dose (0 h), 1, 2, 3 and 24 h post-dose on Day 1 and Day 14 of each period.Population: Pharmacokinetic Population.
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)
Outcome measures
| Measure |
Placebo
n=39 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
Pharmacokinetic Parameter of Time to Maximum Observed Plasma Concentration (Tmax) on Day 1 and 14
Day 1
|
2.0000 h
Interval 0.983 to 3.033
|
—
|
|
Pharmacokinetic Parameter of Time to Maximum Observed Plasma Concentration (Tmax) on Day 1 and 14
Day 14
|
2.9833 h
Interval 0.983 to 3.083
|
—
|
SECONDARY outcome
Timeframe: Start of study treatment (Day 1 of first period) up to follow up, for up to 28 days.Population: All Subjects Population.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE
Any AE
|
8 Participants
|
9 Participants
|
|
Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE
Any SAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Any Adverse Event (AE), Serious Adverse Event or Drug-related AE
Drug- related AE
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose) and Day 14 (pre-dose)Population: All Subjects Population.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings
Abnormal - Not clinically significant, Day 1
|
6 Participants
|
3 Participants
|
|
Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings
Abnormal - Not clinically significant, Day 14
|
2 Participants
|
2 Participants
|
|
Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings
Abnormal - Clinically significant, Day 1
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings
Abnormal - Clinically significant, Day 14
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings
No result, Day 1
|
2 Participants
|
2 Participants
|
|
Number of Participants With Abnormal (Both Not Clinically Significant and Clinically Significant) Electrocardiogram (ECG) Findings
No result, Day 14
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 14 of each periodPopulation: All Subjects Population.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
Number of Participants With Haematology Abnormalities of Potential Clinical Importance (PCI) at Any Time During Treatment
Total neutrophils, PCI- Low
|
1 Participants
|
2 Participants
|
|
Number of Participants With Haematology Abnormalities of Potential Clinical Importance (PCI) at Any Time During Treatment
Lymphocytes, PCI- Low
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 14 of each periodPopulation: All Subjects Population.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 14 of each periodPopulation: All Subjects Population.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
|
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
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 1 and Day 14 of each periodPopulation: All Subjects Population.
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.
Outcome measures
| Measure |
Placebo
n=38 Participants
Eligible participants received matching placebo to SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 Participants
Eligible participants received intranasal spray of SB-705498 12 mg once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
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
|
1 Participants
|
|
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
|
2 Participants
|
|
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
|
14 Participants
|
Adverse Events
Placebo
SB-705498 12 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=38 participants at risk
Participants received repeat doses of matching placebo once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
SB-705498 12 mg
n=39 participants at risk
Participants received repeat doses of intranasal spray of SB-705498 12 milligram (mg) as an active intervention once daily for 14 days in each of the 2 treatment periods, where participants were randomized to any of the two treatment sequences (active/placebo or placebo/active) separated by at least 4 weeks of washout period.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
5.1%
2/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.6%
1/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
2.6%
1/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
|
2.6%
1/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
0.00%
0/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
2.6%
1/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
2.6%
1/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
0.00%
0/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Infections and infestations
Upper respiratory tract infection
|
2.6%
1/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
7.7%
3/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Infections and infestations
Tonsillitis
|
2.6%
1/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
0.00%
0/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Nervous system disorders
Dizziness
|
2.6%
1/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
2.6%
1/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Nervous system disorders
Headache
|
0.00%
0/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
2.6%
1/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Nervous system disorders
Paraesthesia
|
2.6%
1/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
0.00%
0/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
2.6%
1/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
2.6%
1/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Injury, poisoning and procedural complications
Rib fracture
|
2.6%
1/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
0.00%
0/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
|
Vascular disorders
Haematoma
|
2.6%
1/38 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
0.00%
0/39 • AE(s) were collected from start of study treatment (Day 1 of first period) up to follow up (up to 28 days)
All Subjects population
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER