A phase II clinical study to assess the effectiveness, safety, tolerability and pharmacokinetics of inhaled GSK2339345 in patients with chronic cough using an aqueous droplet inhaler.
- Conditions
- chronic idiopathic coughMedDRA version: 17.0 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2012-004891-20-GB
- Lead Sponsor
- GlaxoSmithKline Research and Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 16
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 < 40 pg/ml (<147 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 4.3.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• Child-bearing potential with negative pregnancy test as determined by serum hCG test at screening or prior to dosing AND
• Agrees to use one of the contraception methods listed in Section 4.3.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow up visit.
• OR has only same-sex partners, when this is her preferred and usual lifestyle.
7. Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 4.3.1. This criterion must be followed from the time of the first dose of study medication until the follow up visit.
8. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
9. AST and ALT < 2xULN; alkaline phosphatase and bilirubin =1.5xULN (isolated bilirubin >1.5xULN i
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method