GSK2339345 Hypertussive Challenge Study

Cough Clinical Trial

Official title:

A Randomised, Double-Blind (Sponsor-Unblind), Placebo Controlled, Cross-Over Study to Investigate the Efficacy, Effect on Cough Reflex Sensitivity, Safety, Tolerability and Pharmacokinetics of Inhaled GSK2339345 in Patients With Chronic Idiopathic Cough Using an Aqueous Droplet Inhaler

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01899768
• Other study ID #: 117270
• Status: Completed
• Phase: Phase 2
• First received: July 11, 2013
• Last updated: August 12, 2016
• Start date: November 2013
• Est. completion date: October 2014

Study information

• Verified date: August 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the effect of GSK2339345 relative to placebo on the number of coughs in patients with Chronic Idiopathic Cough (CIC) administered by an Aqueous Droplet Inhaler (ADI). The primary aim is to investigate the efficacy of GSK2339345 on reducing objective cough frequency in CIC patients. The secondary aim of this study is to investigate the efficacy of GSK2339345 in inhibiting a hypertussive cough response elicited by capsaicin and citric acid in CIC patients which have a hyperresponsive cough reflex.

Following the screening visit, all eligible subjects will attend the unit for dosing at Visits 1-7. At Visits 1, 2 and 3 (Part A of the study), subjects will receive two doses of either GSK2339345 or placebo, 4 hours apart and will undergo 8 hours of cough monitoring. At Visits 4 and 5 (Part B of the study) and Visits 6 and 7 (Part C of the study), subjects will be administered a single dose of either GSK2339345 or placebo. Subjects will then undergo capsaicin (Part B) or citric acid (Part C) tussive challenge and will undergo cough monitoring for 1 hour post dose.

The maximum study duration will be approximately 11 weeks, including 3 weeks screening and 2 weeks follow-up. Approximately 30 patients will be randomised into the study, such that approximately 24 patients complete dosing and critical assessments.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• 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.

• 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.

• Male/females aged >=18 years old, at the time of signing the informed consent.

• Non-smoker for at least 6 months with a cumulative history of <= 10 pack years. Pack years = (No. of cigarettes smoked/day/20) x (No. of years smoked).

• Body weight >= 50 kilograms.

• 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 > 40 milli international unit/milliliter (mL) and estradiol < 40 picogram/ml (<147 picomoles/Liter [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 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 to4 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 human chorionic gonadotropin test at screening or prior to dosing and Agrees to use one of the contraception methods 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.

• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until the follow up visit.

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

• Aspartate amino transferase and alanine amino transferase < 2xupper limit of normal (ULN); alkaline phosphatase and bilirubin <= 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• Based on averaged QT interval corrected (QTc) values of triplicate electrocardiograms (ECGs) obtained over a brief recording period: QTc using Fridericia's formula (QTcF) < 450 millisecond.

• A 24 hour Holter ECG at screening that demonstrates no clinically significant abnormalities or finding that could interfere with interpretation of the study results, when assessed by an appropriately trained and experienced reviewer.

Exclusion Criteria Based Upon Medical Histories

• Subjects who have evidence of current asthma, as confirmed by the Investigator or designee.

• Subjects with any clinically significant respiratory condition or lung pathology that could cause cough (apart from chronic idiopathic cough).

• Known lung cancer or other active malignancy, or history of.

• Subjects with current or a chronic history of cardiovascular disease (including uncontrolled hypertension, ischemic heart disease, angina, myocardial infarct, congestive heart failure, and stroke).

• Subjects with current central nervous system / peripheral nervous system conditions e.g. epilepsy and myasthenia gravis.

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• Any subject with a respiratory tract infection within 4 weeks of screening.

• 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.

• 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 grams of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

• Any subject who has a history of an allergic reaction to a local anesthetic. 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 GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.

• Any subject who has a known hypersensitivity to capsaicin or citric acid. Exclusion Criteria Based Upon Diagnostic Assessment

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.

• 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.

• FEV1 less than 80% of the predicted normal value prior to first dosing of the study

• Any subject who does not reach C5 following an oral inhalation of capsaicin at a dose level of 250 micromolar at screening.

• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

• A positive pre-study drug/alcohol screen. Other Exclusion Criteria

• Subjects who are unable to use the inhaler satisfactorily.

• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

• Lactating females.

• 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).

• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cough

Intervention

Drug:
• GSK2339345
Clear colorless solution in clear glass vial for oral inhalation via aqueous droplet inhaler with unit dose strength of 1000 microgram (mcg) inhaled in two actuations.
• Placebo
Clear colorless solution of 0.9% sodium chloride for oral inhalation via aqueous droplet inhaler inhaled in two actuations.

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Belfast
United Kingdom	GSK Investigational Site	Manchester	Lancashire

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	North West Lung Centre

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total cough counts in Part A.	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) will be done to evaluate the effect of a single dose of GSK2339345 versus placebo on objective cough counts in patients with chronic idiopathic cough. Coughs will be counted by a cough monitor fitted to subjects for 8 hours post Dose 1.	3 weeks	No
Secondary	Number of coughs following each dose of capsaicin, following a single dose of GSK2339345 or placebo	The cough count will be performed by a cough monitor fitted to subjects for 1 hour post dose	2 weeks	No
Secondary	Number of coughs following each dose of citric acid, following a single dose of GSK2339345 or placebo	The cough count will be performed by a cough monitor fitted to subjects for 1 hour post dose	2 weeks	No
Secondary	Cough counts following GSK2339345 or placebo at Visits 1, 2 and 3 over shorter epochs (e.g. 1 hour or 15 minute intervals)	The cough count will be performed by a cough monitor fitted to subjects for 8 hours post dose	3 weeks	No
Secondary	Urge to cough visual analogue scale (VAS) 1 hour post-last dose at Visits 1, 2 and 3	Subjects will be asked to subjectively assess their urge to cough using a VAS	3 weeks	No
Secondary	Cough severity VAS 1 hour post-last dose at Visits 1, 2 and 3	Subjects will be asked to subjectively assess their cough severity using a VAS	3 weeks	No
Secondary	To assess the safety profile of GSK2339345 versus placebo	Safety parameters include: Adverse events, vital signs (including systolic and diastolic blood pressure and heart rate.), electrocardiograms (ECG), body temperature, laboratory assessments (including haematology, clinical chemistry and cardiac troponin), and forced expiratory volume in 1 second (FEV1) as a measure of lung function, and oropharyngeal sensate changes (four point scale).	8 weeks	No
Secondary	The systemic pharmacokinetics (PK) profile of GSK2339345.	PK parameters include: Area under concentration-time curve from time zero to 1 hour (AUC [0 to 1]), AUC from time zero to 4 hours (AUC [0 to 4]), AUC from time zero to 24 hours (AUC [0 to 24]), maximum observed concentration (Cmax), and time of occurrence of Cmax (Tmax).	PK samples will be collected at pre-dose, 2 minutes (mins), 5 mins, 10 mins, 30 mins, 1 hour, and 2 hours post dose 1 at visits 1, 2 and 3.	No

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.