Two part study investigating the effects of SB-705498 in chronic cough

• Conditions: Chronic cough; MedDRA version: 14.0Level: LLTClassification code 10066656Term: Chronic coughSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2010-021642-22-GB
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12-30
• Last Update Posted: 25 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

1. AST, ALT, alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
2. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination and laboratory tests, with the exception of chronic cough (chronic cough applies to Part B only). A subject 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. Part B only: Idiopathic or chronic cough resistant to treatment targeted at potential triggers.
4. Male or female between 30 -75 (part A), and 18 - 75 (part B) years of age inclusive, at the time of signing the informed consent.
5. A female subject is eligible to participate if she:
• Is of non-childbearing potential defined as females with a documented hysterectomy; 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 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal 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 postmenopausal
status, they can resume use of HRT during the study without use of a
contraceptive method.
• Is of child-bearing potential, and agrees to use one of the contraception methods listed in Section 8.1 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 84 days post-last dose.
• Has undergone tubal ligation and agrees to perform a pregnancy test at time points specified in the Time and Events Table, Section 4.6.
6. Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 84 days post-last dose.
7. Non-smoker for at least 6 months with a pack history =5pack years (Pack years = (No. of cigarettes smoked/day/20) x No. of years smoked).
8. Body weight = 50 kg and BMI within the range 19 – 32.0 kg/m2 (inclusive).
9. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
10. Single QTcB < 450 msec; or QTcB < 480 msec in subjects with Bundle Branch Block.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified