Chronic cough MedDRA version: 14.0 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: SB-705498
Product Code: SB-705498
Pharmaceutical Form: Tablet
Current Sponsor code: SB-705498
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pha
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. AST, ALT, alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 40 MlU/ml and estradiol =65 years) yes F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
Exclusion criteria: 1. History of a positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or at screening. 2. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 3. History of confirmed positive pre-study drug/alcohol screen. 4. Part A only: Positive test for HIV antibody. 5. History of regular alcohol consumption within 6 months of the study defined as: • An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits. 6. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 7. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 8. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. 9. Known lung cancer or other active malignancy, or history of. 10. Current treatment with oral corticosteroids or other immunosuppressive agents. 11. FEV1 less than 80% of the predicted value prior to dosing. 12. Any subject who does not reach C5 following an oral inhalation challenge of capsaicin at a dose level of 250 µM. 13. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. 14. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. 15. Pregnant females as determined by positive hCG test at screening or prior to dosing. 16. Lactating females. 17. Unwillingness or inability to follow the procedures outlined in the protocol. 18. Subject is mentally or legally incapacitated. 19. Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. 20. Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: To determine the systemic exposure following a single oral dose of 400mg SB-705498 (4 x 100mg tablets). To determine the capsaicin concentration required to achieve C5 following a single dose of SB-705498 or placebo. Part B: To determine the capsaicin concentration required to achieve C5 following a single dose of SB-705498 or placebo. To assess the effect of SB-705498 or placebo on 24 hour ambulatory cough counts.;Secondary Objective: Part A: To determine the capsaicin concentration required to achieve C2 following a single dose of SB-705498. To assess the safety tolerability of a single oral dose of SB-705498. Part B: To assess the effect of SB-705498 or placebo on the Cough Specific Quality of Life questionnaire (CQLQ). To determine the capsaicin concentration required to achieve C2 following a single dose of SB-705498 or placebo. To assess the effect of SB-705498 or placebo on the urge to cough, following capsaicin challenge over a 24 hour period post dose. To determine the capsaicin concentration required to achieve C5, 24h post-dose, following a single dose of SB-705498 or placebo. To determine the capsaicin concentration required to achieve C2, 24 h post-dose, following a single dose of SB-705498 or placebo. To assess the safety tolerability of a single oral dose of SB-705498 .;Primary end point(s): Part A: PK exposure following 10 hour sampling of a single dose of SB-705498.Capsaicin concentration required to achieve C5 following a single dose of SB-705498 at Tmax as compared to baseline. Part B: To determine the capsaicin concentration required to achieve C5 following a single dose of SB-705498 or placebo. 24 hour cough count following single dose of SB-705498 as compared to placebo.;Timepoint(s) of evaluation of this end point: Part A: PK sampling will be performed at various intervals over the course of Day 1. Part B: Capsaicin challenge will be performed at 2 hours following dosing with study drug on Day 1 of both treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Capsaicin concentration required to achieve C2 following a single dose of SB-705498 at Tmax as compared to baseline. - Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology and clinical biochemistry. - Changes in the CQLQ following a single dose of SB-705498 compared to placebo. - Capsaicin concentration required to achieve C2 following a single dose of SB-705498 at Tmax as compared to baseline. - Urge to cough VAS following single dose of SB-705498. - Capsaicin concentration required to achieve C5 following a single dose of SB-705498 at - 24 hours as compared to baseline. - Capsaicin concentration required to achieve C2 following a single dose of SB-705498 at 24 hours as compared to baseline. - Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology and clinical biochemistry. ;Timepoint(s) of evaluation of this end point: The intervals of endpoint measurement vary throughout the study, by endpoint (as is normal for a clinical study) relative to when dosing with study drug occurs. Intervals range from a 30minute basis on each day of dosing, up to 14 days post last dose in each treatment period. | — |
Countries
United Kingdom
Contacts
Public ContactClincial Trails Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed