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SB-705498

Phase 2

Rhinitis | Small molecule | Other |GSK plc|Last Updated: Sep 13, 2019

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDBiomarker
Total Trials6
Total Enrollment260
FDA Designations
No designations recorded
Clinical Trials (6)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01424397Intranasal SB-705498 in Allergic Rhinitis (AR) PatientsPHASE2 COMPLETED 70Apr 14, 2011Jul 7, 2011Sep 13, 20191 Austria
NCT01476098A Study to Investigate the Effect of SB-705498 on Chronic CoughPHASE2 COMPLETED 21Apr 1, 2011Jan 1, 2012Dec 1, 20161 United Kingdom
NCT01424514SB705498 Proof of Concept Chamber Challenge in Subjects With Non Allergic RhinitisPHASE2 COMPLETED 40Dec 1, 2010Apr 18, 2011Jan 29, 20181 Canada
NCT01439308Intranasal SB-705498 in Non-allergic Rhinitis PatientsPHASE2 COMPLETED 40Dec 1, 2009May 1, 2010Dec 1, 20161 Netherlands
NCT00907933Intranasal SB-705498 in Healthy VolunteersPHASE1 COMPLETED 44Nov 10, 2008Feb 11, 2009Jul 13, 20171 United Kingdom
NCT00731250A Study To Assess The Effect Of SB-705498 In A Capsaicin Challenge ModelPHASE1 COMPLETED 45Jul 22, 2008Mar 31, 2009Jul 13, 20171 Netherlands
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Study Endpoints
Primary Endpoints
Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8
Day 8 of each treatment period

Nasal symptoms (nasal congestion, rhinorrhoea, itching and sneezing) were scored on a scale from 0 to 3 where 0= absent symptoms, 3 = severe symptoms. TNSS was calculated as the sum of the response for all 4 individual nasal symptom scores. TNSS ranged from 0 to 12, where 0=absent symptoms, 3=severe symptoms. Higher the score, more severe the symptoms. Weighted mean (WM) of TNSS and its individual components (nasal congestion, rhinorrhoea, itching and sneezing) are presented on Day 8. Weighted mean was calculated over the time interval 0 to 4 hours after start of allergen chamber challenge by calculating the area under the curve of TNSS/component from time of the first observation to time of the last observation (AUC \[tf-t1 hours\]) using the trapezoidal rule, and then dividing by the actual relevant time interval (tf-t1) required by participant to complete the chamber challenge assessments. A Bayesian analysis was conducted to derive the posterior probability for TNSS.

Pharmacokinetic parameter of area under the plasma concentration-time curve from time zero to 4 hours AUC(0-4) and from time zero (pre-dose) to last time of quantifiable concentration AUC(0-t)- Part A
pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose

AUC(0-4) is a measure of the average amount of study drug in the blood plasma over a period of 4 hours after the dose and AUC(0-t) is a measure average amount of study drug in the blood plasma over a period of last time of quantifiable concentration. Both the parameters were calculated by standard non-compartmental analysis. Blood samples for PK analysis were obtained at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose.

Maximum observed concentration (Cmax) following 10 hour sampling of a single dose of SB-705498 - Part A
pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose Day 1

Cmax is defined as the maximum or "peak" concentration of a drug observed after its administration. Cmax is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. It was calculated by standard non-compartmental analysis. Blood samples for PK analysis were obtained at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose.

Time of occurrence of Cmax (Tmax) following 10 hour sampling of a single dose of SB-705498 -Part A
pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose

Tmax is defined as the time of occurrence of Cmax. Blood samples for PK analysis were obtained at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose.

Capsaicin concentration required to achieve Five or more coughs (C5) following a single dose of SB-705498 at Tmax as compared to baseline- Part A
Day -1 (baseline) and Day 1 (2 hours post dose

The concentration of capsaicin required to elicit 5 coughs was analyzed. The distributional properties were investigated, and the endpoint was logged (base 2) for analysis and the difference from Day -1 (baseline) was taken (equivalent to ratio on log scale).

Capsaicin concentration required to achieve C5 following a single dose of SB-705498 or placebo- Part B
Day -1, Day 1 (2hrs and 24 hrs post dose)

The concentration of capsaicin required to elicit 5 coughs was analyzed. The distributional properties were investigated, and the endpoint was logged (base 2) for analysis and the difference from Day -1 (baseline) was taken (equivalent to ratio on log scale).

Cough Count Per 24 hour following single dose of SB-705498 as compared to placebo- Part B
Day -1 and Day 1 (2 and 24 hours)

24 hour cough count (rate/h) following single dose of SB-705498 as compared to placebo were analyzed by first log transforming the cough counts taken on Day -1 and on Day 1 of each period in the 24 hours post dose. The cough count rates were log(10) transformed.

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.

Assessment of total symptom score (TSS) after unilateral, incremental dose, intranasal challenge with capsaicin
0-4hours following dosing
Assessment of total Ipsilateral secretion's weight after unilateral, incremental dose, intranasal challenge with capsaicin
0-4hours following dosing
Safety and tolerability (Electrocardiogram, vital signs, lab tests, AEs and nasal tolerability
Various
Symptom scores and secretion weights
up to 83 days
Secondary Endpoints
Mean TNSS and Its Individual Components From Day 4 to Day 8
pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge [1 hour (hr)] on Day 8 of each treatment period
Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR)
Day 8
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo
Day 8
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelCROSSOVER
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
SB-705498EXPERIMENTALExperimental
Fluticasone PropionateACTIVE_COMPARATORActive Comparator
PlaceboPLACEBO_COMPARATORPlacebo Comparator
SB-705498+FPEXPERIMENTALExperimental
Arm 1PLACEBO_COMPARATORincremental doses capsaicin
Arm 2ACTIVE_COMPARATORincremenrtal doses casaicin
Part 1 - Arm 1EXPERIMENTALHVTs
Part 2 - Arm 3PLACEBO_COMPARATORHVTs
Part 1 - Arm 2EXPERIMENTALHVTs
Part 1 - Arm 3EXPERIMENTALHVTs
Part 1 - Arm 4EXPERIMENTALHVTs
Part 1 - Arm 5EXPERIMENTALHVTs
Part 1 - Arm 6PLACEBO_COMPARATORHVTs
Part 2 - Arm 1EXPERIMENTALHVTs
Part 2 - Arm 2EXPERIMENTALHVTs
PART 1-Visit 1-PlaceboPLACEBO_COMPARATOREligible subjects will receive matching placebo tablets
PART 1-Visit 1-CapsaicinEXPERIMENTALEligible subjects will receive incremental capsaicin doses
PART 1-Visit 2-PlaceboPLACEBO_COMPARATOREligible subjects will receive matching placebo tablets
PART 1-Visit 2-CapsaicinEXPERIMENTALEligible subjects will receive maximum capsaicin dose
PART 1-Visit 3-PlaceboPLACEBO_COMPARATOREligible subjects will receive matching placebo tablets
PART 1-Visit 3-CapsaicinEXPERIMENTALEligible subjects will receive matching placebo tablets incremental capsaicin doses
PART 2-Visit 1-PlaceboPLACEBO_COMPARATOREligible subjects will receive matching placebo tablets
PART 2-Visit 1-SB-705498EXPERIMENTALEligible subjects will receive SB-705498 tablets
PART 2-Visit 2-CapsaicinEXPERIMENTALEligible subjects will receive matching placebo tablets incremental capsaicin doses
Interventions
NameTypeDescription
SB-705498DRUG12mg intranasal
FPDRUG200ug intranasal
placeboDRUGplacebo intranasal
CaspaicinOTHERSubjects will be challenged with 0.5 µg, 5.0 µg and 50 µg intranasal dose
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Eligibility Criteria
Age Range18 Years — 65 Years
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: 1. Diagnosis of AR, as determined by the presence of rhinitis symptoms that last for several months per year, for more than 1 year and are not attributed to allergy, infections or nasal abnormalities. 2. TNSS score of \>=4 following screening allergen challenge chamber. 3. Posit...

Countries:AustriaUnited KingdomCanadaNetherlands
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Competitive Landscape -Allergic Rhinitis 4 trials