Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
SB705498 · 9 trials · 4 indications
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.
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.
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.
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.
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).
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).
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.
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.
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.
Pain intensity was assessed using VAS. These assessments were then summarized to give a weighted mean score. The VAS was a subjective assessment of post-operative pain intensity. The participants rated the pain intensity at the time of assessment by marking a line on a 100 millimeter (mm) (0 to 100 mm) long scale. A line placed on the extreme left (0 mm) indicated no pain and extreme right (100 mm) indicated worst pain imaginable. This scale has no subscales. Only those participants available at the specified time points were analyzed.
| Arm | Type | Description |
|---|---|---|
| SB-705498 | EXPERIMENTAL | Experimental |
| Fluticasone Propionate | ACTIVE_COMPARATOR | Active Comparator |
| Placebo | PLACEBO_COMPARATOR | Placebo Comparator |
| SB-705498+FP | EXPERIMENTAL | Experimental |
| Arm 1 | PLACEBO_COMPARATOR | incremental doses capsaicin |
| Arm 2 | ACTIVE_COMPARATOR | incremenrtal doses casaicin |
| SB705498 400 mg | EXPERIMENTAL | Eligible participants received a single dose of SB705498 400 milligram (mg) capsules (2 x 200 mg capsules plus 2 placebo capsules) via oral route and were followed up to a maximum of 14 days. |
| SB705498 1000 mg | EXPERIMENTAL | Eligible participants received a single dose of SB705498 1000 mg capsules (2 x 200 mg capsules plus 2 x 300 mg capsules) via oral route and were followed up to a maximum of 14 days. |
| Co-Codamol | EXPERIMENTAL | Eligible participants received a single dose of Co-codamol capsules (2 x Paracetamol Ph Eur 500 mg, codeine phosphate hemihydrate Ph Eur 12.8 mg plus two placebo capsules) via oral route and were followed up to a maximum of 14 days. |
| study population | EXPERIMENTAL | All subjects will receive 1%, 3%, 5% (w/w) of SB705498 and a placebo comparator |
| Part 1 - Arm 1 | EXPERIMENTAL | HVTs |
| Part 2 - Arm 3 | PLACEBO_COMPARATOR | HVTs |
| Part 1 - Arm 2 | EXPERIMENTAL | HVTs |
| Part 1 - Arm 3 | EXPERIMENTAL | HVTs |
| Part 1 - Arm 4 | EXPERIMENTAL | HVTs |
| Part 1 - Arm 5 | EXPERIMENTAL | HVTs |
| Part 1 - Arm 6 | PLACEBO_COMPARATOR | HVTs |
| Part 2 - Arm 1 | EXPERIMENTAL | HVTs |
| Part 2 - Arm 2 | EXPERIMENTAL | HVTs |
| PART 1-Visit 1-Placebo | PLACEBO_COMPARATOR | Eligible subjects will receive matching placebo tablets |
| PART 1-Visit 1-Capsaicin | EXPERIMENTAL | Eligible subjects will receive incremental capsaicin doses |
| PART 1-Visit 2-Placebo | PLACEBO_COMPARATOR | Eligible subjects will receive matching placebo tablets |
| PART 1-Visit 2-Capsaicin | EXPERIMENTAL | Eligible subjects will receive maximum capsaicin dose |
| PART 1-Visit 3-Placebo | PLACEBO_COMPARATOR | Eligible subjects will receive matching placebo tablets |
| PART 1-Visit 3-Capsaicin | EXPERIMENTAL | Eligible subjects will receive matching placebo tablets incremental capsaicin doses |
| PART 2-Visit 1-Placebo | PLACEBO_COMPARATOR | Eligible subjects will receive matching placebo tablets |
| PART 2-Visit 1-SB-705498 | EXPERIMENTAL | Eligible subjects will receive SB-705498 tablets |
| PART 2-Visit 2-Capsaicin | EXPERIMENTAL | Eligible subjects will receive matching placebo tablets incremental capsaicin doses |
| Name | Type | Description |
|---|---|---|
| SB-705498 | DRUG | 12mg intranasal |
| FP | DRUG | 200ug intranasal |
| placebo | DRUG | placebo intranasal |
| SB705498 400 mg | DRUG | SB705498 400 mg |
| SB705498 1000 mg | DRUG | SB705498 1000 mg |
| Co-Codamol | DRUG | Co-Codamol |
| SB705498 | DRUG | 1%, 3% and 5% (w/w) of SB705498 will be used in part A of the study. One dose will then be selected based on criteria explained in the protocol for use in Part B of the study. |
| Caspaicin | OTHER | Subjects will be challenged with 0.5 µg, 5.0 µg and 50 µg intranasal dose |
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...
SB705498 is an investigational small molecule developed by GSK plc (ticker GSK). It has been studied in clinical trials for atopic dermatitis, acute migraine, rhinitis, and toothache, with dermatology as its main therapeutic area. It is not an approved medicine and remains in clinical development.
SB705498 has been studied in trials for atopic dermatitis, acute migraine, rhinitis, and toothache. The completed studies include topical application in healthy volunteers and atopic dermatitis, plus intranasal and oral dosing in non-allergic rhinitis and chronic cough. It is investigational and has no approved use.
SB705498 is developed by GSK plc, which trades under the ticker GSK. GSK sponsored the clinical trial program for the compound across dermatology and respiratory indications.
SB705498 is in Phase 1 development overall, though individual completed studies have been listed as Phase 2. It is investigational and has not been approved by the FDA. All six of its recorded trials are completed, and none are currently active.
Six completed trials have studied SB705498, including NCT01673529, a Phase 1 topical study in healthy volunteers in the United Kingdom; NCT01476098, a Phase 2 chronic cough study in the United Kingdom; NCT01439308, a Phase 2 intranasal study in non-allergic rhinitis in the Netherlands; and NCT01424514, a Phase 2 chamber challenge study in non-allergic rhinitis in Canada.
Yes. SB705498, SB-705498, and SB705498 400 mg all refer to the same GSK compound. The hyphenated form SB-705498 appears in several trial titles, while SB705498 is the unhyphenated name used in others. The 400 mg reference denotes a dose strength studied in trials.