chronic idiopathic cough MedDRA version: 17.0 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000004855
Conditions
Interventions
Product Name: GSK2339345
Product Code: GSK2339345
Pharmaceutical Form: Inhalation vapour, solution
INN or Proposed INN: GSK2339345
Curre
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Chronic Idiopathic Cough patients according to the criteria listed below, determined by a responsible and experienced physician, based on a medical evaluation: • Idiopathic cough defined as chronic cough resistant to treatment targeted at potential triggers. • Chronic cough defined as cough lasting for more than 8 weeks (British Thoracic Society, 2006). 2. A patient with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. 3. Male/females aged =18 years old, at the time of signing the informed consent. 4. Non-smoker for at least 6 months with a cumulative history of = 20 pack years. • Pack years = (No. of cigarettes smoked/day/20) x (No. of years smoked) 5. Body weight = 50 kg. 6. A female subject is eligible to participate if she is of: • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy [for this definition, “documented” refers to the outcome of the investigator's/designee’s review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol 1.5xULN i
Exclusion criteria
Exclusion criteria: Criteria Based Upon Medical Histories 1. Subjects who have evidence of current asthma, as confirmed by the Investigator or designee. 2. Subjects with any clinically significant respiratory condition or lung pathology that could cause cough (apart from chronic idiopathic cough). 3. Known lung cancer or other active malignancy, or history of. 4. Subjects with current or a chronic history of cardiovascular disease (including uncontrolled hypertension, ischaemic heart disease, angina, myocardial infarct, congestive heart failure, stroke). 5. Subjects with current central nervous system / peripheral nervous system conditions e.g. epilepsy and myasthenia gravis. 6. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 7. Any subject with a respiratory tract infection within 4 weeks of screening. 8. Radiological imaging prior to the study, including chest X-rays, that have shown any evidence of clinically significant lung disease, as judged by the Investigator or designee. 9. 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. 10. Any subject who has a history of an allergic reaction to a local anaesthetic. 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. 11. Any subject who has a known hypersensitivity to capsaicin or citric acid. Criteria Based Upon Diagnostic Assessments 12. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. 13. Any subject who, upon oropharyngeal examination, is deemed by the Investigator to be unsuitable for oropharyngeal sensation assessments. This includes any injuries to the mucosa of the mouth or pharynx that could potentially increase systemic absorption e.g. oropharyngeal candidiasis. 14. FEV1 less than 80% of the predicted normal value prior to first dosing of the study. 15. Any subject who does not reach C5 following an oral inhalation of capsaicin at a dose level of 250 µM at screening. 16. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. 17. A positive pre-study drug/alcohol screen. Other Criteria 18. Subjects who are unable to use the inhaler satisfactorily. 19. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. 20. Lactating females. 21. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: EFFICACY: To evaluate the effect of a single dose of GSK2339345, administered on two occasions, four hours apart, versus placebo on objective cough counts in patients with chronic idiopathic cough. ; Primary end point(s): EFFICACY: Total cough counts (8 hours of recording) at Visits 1, 2 and 3 (4 hours of post-dose recording for each of the two doses administered). ;Timepoint(s) of evaluation of this end point: Continuous cough monitoring 8 hours (4 hours post-dose for each of the two doses administered) post-first dose at visits 1, 2 & 3.; Secondary Objective: TUSSIVE CHALLENGE: To evaluate the effect of single dose GSK2339345 versus placebo on cough response to tussive challenge in patients with chronic idiopathic cough. EFFICACY: To assess the duration of effect of GSK2339345 versus placebo on objective cough counts in patients with chronic idiopathic cough. To assess the effect of GSK2339345 versus placebo on the urge to cough in patients with chronic idiopathic cough. To assess the effect of GSK2339345 versus placebo on the severity of cough in patients with chronic idiopathic cough. SAFETY: To assess the safety and tolerability of GSK2339345 versus placebo in patients with chronic idiopathic cough. PHARMACOKINETICS: To evaluate the systemic pharmacokinetics of GSK2339345 in patients with chronic idiopathic cough. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): TUSSIVE CHALLENGE: Number of coughs following each dose of capsaicin, following a single dose of GSK2339345 or placebo. Number of coughs following each dose of citric acid, following a single dose of GSK2339345 or placebo. EFFICACY:Cough counts following GSK2339345 or placebo at Visits 1, 2 and 3 over shorter epochs (e.g. 1 hour or 15 minute intervals). Urge to cough VAS 1 hour post-last dose at Visits 1, 2 and 3. Cough severity VAS 1 hour post-last dose at Visits 1, 2 and 3. SAFETY: Safety parameters: AEs, vital signs, ECGs, body temperature, laboratory assessments (including haematology, clinical chemistry and cardiac troponin), FEV1; and oropharyngeal sensate changes (four point scale). PHARMACOKINETICS: Plasma concentrations of GSK2339345 and derived pharmacokinetic parameters including Cmax, tmax, AUC(0-1) and AUC(0-4) as appropriate and predicted AUC(0-24) following two repeated doses where data allow, at Visits 1, 2 and 3. ; Timepoint(s) of evaluation of this end point: TUSSIVE CHALLENGE: Continuous cough monitoring for 1 hour post-dose on visits 4, 5, 6 & 7. EFFICACY:Cough counts following GSK2339345 or placebo at Visits 1, 2 and 3 for 8 hours post dose (total and also divided into shorter epochs (e.g. 1 hour or 15 minute intervals). Urge to cough VAS 1 hour post-last dose at Visits 1, 2 and 3. Cough severity VAS 1 hour post-last dose at Visits 1, 2 and 3 (as above). SAFETY:Up to a minimum of 1 hour post-dose during visits 1, 2, 3, 4, 5, 6 & 7. Period of monitoring and assessments may continue for longer in the event of any safety concerns. Follow-up of each subject will occur 7-14days following the last dose. PHARMACOKINETICS(PK):Blood samples for PK analysis will be collected at intervals from pre-dose until 2 hours post each dose during visits 1 | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed