GSK2339345 Hypertussive Challenge Study

NCT01899768 | Completed Phase 2 Results

• 1 other identifier: 117270
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Cough

Keywords

efficacy; hypertussive challenge; voltage gated sodium channels (VGSC); anaesthesia; Safety and tolerability; capsaicin challenge; cough; citric acid challenge; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Total Cough Count Over 8 Hours at Visits 1, 2 and 3 (Part A)

  Total cough count (8 hours \[hr\] of recording) was conducted at Visits 1, 2 and 3. Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count was calculated as the sum of two four hour cough count totals, with the first four hours starting from the time of the first dose and the second four hours starting at the time of the second dose. The cough counts were sum-up by the treatments received by the participants. Number of coughs in 8 hr period was loge transformed and used for the analysis. Values were imputed pro-rata if 8 hr epoch was less than 8 hr. Mean of the total cough counts recorded post dose of every treatment i.e. placebo or GSK2339345 1000mcg was reported.

  Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A)

• Total Cough Count Excluding Transient Coughs Over 8 Hours at Visits 1, 2 and 3 (Part A)

  Total cough count (8 hr of recording) was conducted at Visits 1, 2 and 3. Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count was calculated as the sum of two four hour cough count totals, with the first 4-hrs starting from the time of the first dose and the second four hours starting at the time of the second dose. The cough counts were sum-up by the treatments received by the participants. Transient cough was the total number of coughs experienced in the two mins from the start of the first inhalation of a dose. Number of coughs excluding transient cough in 8 hr period was loge transformed and used for the analysis. Values were imputed pro-rata if 8 hr epoch was less than 8 hr. Mean of the total cough counts excluding transient cough recorded post dose of every treatment i.e. placebo or GSK2339345 1000 mcg was reported.

  Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A)

Secondary Outcomes (34)

• Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)

  From the start of study treatment and until the follow-up contact (up to 8 Weeks)

• Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C

  Pre-dose, 5 min, 15 min (only in Part A), 30 min, and 1 hr post each dose administered in Parts A, B and C (up to 8 weeks)

• Mean Heart Rate at the Indicated Time Points in Parts A, B and C

  Pre-dose, 5 min, 15 min (only in Part A), 30 min, and 1 hr after each dose administered in Parts A, B and C (up to 8 weeks)

• Mean Body Temperature at the Indicated Time Points in Parts A, B and C

  1 hr post the second dose administered in Part A and 1 hr post each dose administered in Parts B and C (up to 8 Weeks)

• Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C

  Pre-dose and 5min to 1 hr after each dose administered in Parts A, B and C (up to 8 Weeks)

Study Arms (3)

Part A

EXPERIMENTAL

Subjects will receive treatment A (placebo) or treatment B (GSK2339345) in 3 visits of part A (one treatment per visit) in one of the following four sequences: ABA, ABB, BAA, and BAB.

Drug: GSK2339345; Drug: Placebo

Part B

EXPERIMENTAL

Subjects will receive treatment A or treatment B in 2 visits of part B (one treatment per visit) in one of the following two sequences: AB and BA. Subjects will then orally inhale 10 microliter (mcL) of a capsaicin solution of strength ranging from 0.49 micromolar (mcM) to 1000 mcM, which will be administered using a breath activated dosimeter approximately 5 minutes post-dosing with treatment A or B at Visits 4 and 5.

Drug: GSK2339345; Drug: Placebo

Part C

EXPERIMENTAL

Subjects will receive treatment A or treatment B in 2 visits of part C (one treatment per visit) in one of the following two sequences: AB and BA. Subjects will then orally inhale 10 mcL of a citric acid solution of strength ranging from 0.03 to 4.0 M, which will be administered using a breath activated dosimeter approximately 5 minutes post-dosing with treatment A or B at Visits 6 and 7.

Drug: GSK2339345; Drug: Placebo

Interventions

GSK2339345 DRUG

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.

Part A; Part B; Part C

Placebo DRUG

Clear colorless solution of 0.9% sodium chloride for oral inhalation via aqueous droplet inhaler inhaled in two actuations.

Part A; Part B; Part C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• North West Lung Centre: collaborator

Study Sites (2)

GSK Investigational Site

Manchester, Lancashire, M23 9LT, United Kingdom

Location

GSK Investigational Site

Belfast, BT9 7AB, United Kingdom

Location

Related 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.

MeSH Terms

Conditions

Cough

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2013
• First Posted: July 15, 2013
• Study Start: November 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: April 5, 2017
• Results First Posted: April 5, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will share

Locations

GB (2)