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GSK2339345 Hypertussive Challenge Study

Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Cough

Intervention: GSK2339345 (Drug); Placebo (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

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.

Clinical Details

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

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

Primary outcome: Total cough counts in Part A.

Secondary outcome:

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

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 visual analogue scale (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

To assess the safety profile of GSK2339345 versus placebo

The systemic pharmacokinetics (PK) profile of GSK2339345.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Locations and Contacts

GSK Investigational Site, Belfast BT9 7AB, United Kingdom

GSK Investigational Site, Manchester, Lancashire M23 9LT, United Kingdom

Additional Information

Starting date: November 2013
Last updated: April 2, 2015

Page last updated: August 20, 2015

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