CoughPhase 1FTIHNCT01494636
The Safety, Tolerability, PK and PD of GSK2339345 in Healthy Subjects
A Phase 1 study testing GSK2339345 (solution), GSK2339345 (nebulised) and Lidocaine in people with Cough, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
This is a First Time in Human (FTIH) study for the sodium channel inhibitor, GSK2339345. The study is split into two parts. Part A will assess the safety and tolerability of the new drug. Part B will assess safety and tolerability as well as the effect of GSK2339345 on induced cough. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Cough
- What is being tested?
- GSK2339345 (solution), GSK2339345 (nebulised) and Lidocaine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Oct 2011to 15 Mar 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- Male between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Male subjects with female partners of child-bearing potential must agree to use an approved method of contraception, (double-barrier method or complete sexual inactivity by abstinence). This criterion must be followed from the time of the first dose of study medication until the follow up visit.
- 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).
- Body weight ≥ 50 kg and BMI within the range 19 - 32.0 kg/m2 (inclusive).
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- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- QTcB< 450 msec
- 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.
Who cannot join
- Hepatitis B or Hepatitis C positive
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- HIV positive
- History of regular alcohol consumption within 6 months of the study
- 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).
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- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- 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.
- Forced Expiratory Volume in one second (FEV1) less than 80% of the predicted value prior to dosing (Part B only)
- Part B only: any subject who does not reach C5 following an oral inhalation challenge of capsaicin at a dose level of 250 μM at screening or Day -1, reaches C5 following an oral inhalation of placebo solution or has known hypersensitivity to capsaicin
- Part A only: any subject who is unable to gargle with placebo solution
- Any subject who is unable to perceive oropharyngeal numbness caused by lidocaine
- 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 candidiasis.
- Any patient with a history of swallowing difficulties.
- 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.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- Breath CO levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Two Part Study to Investigate the Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2339345 in Healthy Subjects. Part A: an Open Label, Dose Escalating, Rinse, Gargle and Spit Study. Part B: a Randomised, Double-blind, Placebo Controlled, Inhaled Dose Escalating Study Using Nebulised Lidocaine for Blinding Purposes.
This is a First Time in Human (FTIH) study for the sodium channel inhibitor, GSK2339345. The study is split into two parts. Part A will assess the safety and tolerability of the new drug. Part B will assess safety and tolerability as well as the effect of GSK2339345 on induced cough.
Read the detailed description
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of GSK2339345 in healthy subjects. GSK2339345 is a blocker of neuronal voltage gated sodium channels in development for the treatment of chronic cough, excessive cough and post-viral and viral (acute) cough. Inhaled pan NaV inhibitors are associated with oropharyngeal sensation perturbation and so this study will establish the potential local sensate effects of GSK2339345 at multiples of the predicted inhaled therapeutic dose. This study also aims to define the maximum tolerated dose of GSK2339345.
Part A of this study will be conducted in healthy volunteers to investigate the safety and tolerability of GSK2339345, in particular examining oropharyngeal sensation perturbation. Part A is an open label, oral, single-dose escalating rinse, gargle and spit study. Assessments of sensate changes will include 4 point scale, assessment of sensation on base of tongue, sensation of temperature, assessment of taste, a water swallow test and assessment of potential paraesthesias. Part A will also include PK assessments to investigate the PK profile of GSK2339345.
Part B of this study is a randomised, double blind, placebo controlled, inhaled dose escalation study over two study days per dose to examine the possible adverse events such as transient mouth, throat and upper airway numbness in healthy volunteers. Similar assessments of sensations to those used in Part A will be performed. The potential for systemic cardiovascular (CV) or central nervous system (CNS) effects will also be assessed. Pharmacodynamic effects of GSK2339345 will be investigated in Part B using a capsaicin cough challenge. The study will investigate whether GSK2339345 can alter the capsaicin cough threshold (as determined by the capsaicin concentration required to induce 2 or more (C2) and 5 or more (C5) coughs) in healthy volunteers. Part B will also include PK assessments to investigate the PK profile of GSK2339345. Placebo will be used as a control and nebulised lidocaine will be used for control and blinding purposes only.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2339345 (solution)Drug
3, 6, 15, 30, 60 and 120 micrograms (proposed doses). 2 alternating cohorts of 6 subjects. Each subject to receive 3 ascending doses with washout of at least 48 hours between doses. Rinse, Gargle and Spit.
GSK2339345 (nebulised)Drug
25, 100, 250, 1000 and 2000 micrograms (proposed doses). Subjects randomised to receive three ascending doses (with each dose given on two consecutive days). Washout of at least 6 days between treatment periods. Nebulised.
Placebo (0.9% sodium chloride solution)Drug
Administered on Day 1 of one of the treatment periods in part B. Randomised. Nebulised.
LidocaineDrug
40mg dose. Administered on Day 2 of one of the treatment periods in part B. Randomised. Nebulised.
| Study group | Role | What they receive |
|---|---|---|
| GSK2339345 (solution) (part A) | Experimental | Part A Receives: Drug: GSK2339345 (solution) |
| GSK2339345/ Placebo/ Lidocaine (nebulised) (part B) | Experimental | Part B Receives: Drug: GSK2339345 (nebulised); Drug: Placebo (0.9% sodium chloride solution); Drug: Lidocaine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in oropharyngeal sensation
Measured by 4 point scale, fingertip electrode assessment, sensation to water temperature, adverse events, water swallow test and assessment of gag reflex
Measured: Dosing to 1 hour post dose
Adverse events (AEs) for all study participants
Measurement of types of AEs reported, severity and relationship to study drug
Measured: Dosing to 24 hours post dose
Assessment of vital signs for all study participants
Triplicate measurements will be taken at screening and pre-dose, single measurements at all other timepoints
Measured: Screening to follow-up
Holter ECG measurement for all study participants
24 hour Holter ECG will be taken at screening
Measured: Screening (Part A and Part B)
12-lead ECG measurements for all study participants
Triplicate measurements will be taken at screening and pre-dose, single measurements at all other timepoints
Measured: Screening to follow-up
Body temperature for all study participants
Measured: Screening, pre-dose, 30 mins post dose, 4 hours post dose, 8 hours post dose and follow-up in each dosing session
Safety laboratory assessments for all study participants
To include haematology and clinical biochemistry assessments
Measured: Part A: Screening, pre-dose, 24 hours post dose and follow-up in each dosing session. Part B: Screening, pre-dose and 8 hours post dose on Day 1, 0 hours and 8 hours post dose on Day 2, follow-up
Cardiac troponin measurements for all study participants
Measured: Part B only: Screening, pre-dose and 24 hours post dose on Day 1
Secondary outcomes (3)
Palatability by identification of solution taste and 11 point scale
Measured: 30 minutes post dose
Systemic pharmacokinetics of GSK2339345 using plasma concentrations of GSK2339345 and derived pharmacokinetic parameters
Measured: Pre-dose to 24 hours post dose
Effect of an inhaled nebulised dose of GSK2339345 on cough response to capsaicin challenge in healthy volunteers
Measured: Part B: Day 2, 10 minutes post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2011 (estimated)
- Study start17 Oct 2011
- Primary completion15 Mar 2012
- Study completion15 Mar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CoughStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01494636
- Sponsor's protocol ID
- 115419
- Acronym
- FTIH
- Status last verified
- Jun 2017
- First submitted
- 17 Nov 2011
- Last updated
- 20 Jun 2017
- Results posted
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two Part Study to Investigate the Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2339345 in Healthy Subjects. Part A: an Open Label, Dose Escalating, Rinse, Gargle and Spit Study. Part B: a Randomised, Double-blind, Placebo Controlled, Inhaled Dose Escalating Study Using Nebulised Lidocaine for Blinding Purposes.
- ClinicalTrials.gov ID
- NCT01494636
- Acronym / sponsor ID
- FTIH / 115419
- Conditions
- Cough
- Keywords
- Capsaicin Challenge, Pharmacodynamics, Safety, Pharmacokinetics, Oral GSK2339345, Tolerability, FTIH, Chronic Cough
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 17 Oct 2011 (actual)
- Primary completion
- 15 Mar 2012 (actual)
- Study completion
- 15 Mar 2012 (actual)
- First posted
- 19 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a First Time in Human (FTIH) study for the sodium channel inhibitor, GSK2339345. The study is split into two parts. Part A will assess the safety and tolerability of the new drug. Part B will assess safety and tolerability as well as the effect of GSK2339345 on induced cough.
Detailed description
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of GSK2339345 in healthy subjects. GSK2339345 is a blocker of neuronal voltage gated sodium channels in development for the treatment of chronic cough, excessive cough and post-viral and viral (acute) cough. Inhaled pan NaV inhibitors are associated with oropharyngeal sensation perturbation and so this study will establish the potential local sensate effects of GSK2339345 at multiples of the predicted inhaled therapeutic dose. This study also aims to define the maximum tolerated dose of GSK2339345.
Part A of this study will be conducted in healthy volunteers to investigate the safety and tolerability of GSK2339345, in particular examining oropharyngeal sensation perturbation. Part A is an open label, oral, single-dose escalating rinse, gargle and spit study. Assessments of sensate changes will include 4 point scale, assessment of sensation on base of tongue, sensation of temperature, assessment of taste, a water swallow test and assessment of potential paraesthesias. Part A will also include PK assessments to investigate the PK profile of GSK2339345.
Part B of this study is a randomised, double blind, placebo controlled, inhaled dose escalation study over two study days per dose to examine the possible adverse events such as transient mouth, throat and upper airway numbness in healthy volunteers. Similar assessments of sensations to those used in Part A will be performed. The potential for systemic cardiovascular (CV) or central nervous system (CNS) effects will also be assessed. Pharmacodynamic effects of GSK2339345 will be investigated in Part B using a capsaicin cough challenge. The study will investigate whether GSK2339345 can alter the capsaicin cough threshold (as determined by the capsaicin concentration required to induce 2 or more (C2) and 5 or more (C5) coughs) in healthy volunteers. Part B will also include PK assessments to investigate the PK profile of GSK2339345. Placebo will be used as a control and nebulised lidocaine will be used for control and blinding purposes only.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GSK2339345 (solution) (part A) | Experimental | Drug: GSK2339345 (solution)Part A |
| GSK2339345/ Placebo/ Lidocaine (nebulised) (part B) | Experimental | Drug: GSK2339345 (nebulised), Drug: Placebo (0.9% sodium chloride solution), Drug: LidocainePart B |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- Male between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Male subjects with female partners of child-bearing potential must agree to use an approved method of contraception, (double-barrier method or complete sexual inactivity by abstinence). This criterion must be followed from the time of the first dose of study medication until the follow up visit.
- 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).
Key exclusion criteria (20 listed)
- Hepatitis B or Hepatitis C positive
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- HIV positive
- History of regular alcohol consumption within 6 months of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2339345 (solution)3, 6, 15, 30, 60 and 120 micrograms (proposed doses). 2 alternating cohorts of 6 subjects. Each subject to receive 3 ascending doses with washout of at least 48 hours between doses. Rinse, Gargle and Spit. | Drug | GSK2339345 (solution) (part A) |
| GSK2339345 (nebulised)25, 100, 250, 1000 and 2000 micrograms (proposed doses). Subjects randomised to receive three ascending doses (with each dose given on two consecutive days). Washout of at least 6 days between treatment periods. Nebulised. | Drug | GSK2339345/ Placebo/ Lidocaine (nebulised) (part B) |
| Placebo (0.9% sodium chloride solution)Administered on Day 1 of one of the treatment periods in part B. Randomised. Nebulised. | Drug | GSK2339345/ Placebo/ Lidocaine (nebulised) (part B) |
| Lidocaine40mg dose. Administered on Day 2 of one of the treatment periods in part B. Randomised. Nebulised. | Drug | GSK2339345/ Placebo/ Lidocaine (nebulised) (part B) |
Primary outcome
Change in oropharyngeal sensation
Time frame: Dosing to 1 hour post dose
Measured by 4 point scale, fingertip electrode assessment, sensation to water temperature, adverse events, water swallow test and assessment of gag reflex
Adverse events (AEs) for all study participants
Time frame: Dosing to 24 hours post dose
Measurement of types of AEs reported, severity and relationship to study drug
Assessment of vital signs for all study participants
Time frame: Screening to follow-up
Triplicate measurements will be taken at screening and pre-dose, single measurements at all other timepoints
Holter ECG measurement for all study participants
Time frame: Screening (Part A and Part B)
24 hour Holter ECG will be taken at screening
12-lead ECG measurements for all study participants
Time frame: Screening to follow-up
Triplicate measurements will be taken at screening and pre-dose, single measurements at all other timepoints
Body temperature for all study participants
Time frame: Screening, pre-dose, 30 mins post dose, 4 hours post dose, 8 hours post dose and follow-up in each dosing session
Safety laboratory assessments for all study participants
Time frame: Part A: Screening, pre-dose, 24 hours post dose and follow-up in each dosing session. Part B: Screening, pre-dose and 8 hours post dose on Day 1, 0 hours and 8 hours post dose on Day 2, follow-up
To include haematology and clinical biochemistry assessments
Cardiac troponin measurements for all study participants
Time frame: Part B only: Screening, pre-dose and 24 hours post dose on Day 1
3 secondary outcomes
Palatability by identification of solution taste and 11 point scale
Time frame: 30 minutes post dose
Systemic pharmacokinetics of GSK2339345 using plasma concentrations of GSK2339345 and derived pharmacokinetic parameters
Time frame: Pre-dose to 24 hours post dose
Effect of an inhaled nebulised dose of GSK2339345 on cough response to capsaicin challenge in healthy volunteers
Time frame: Part B: Day 2, 10 minutes post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Results for study 115419 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK2339345 (solution), GSK2339345 (nebulised) and Lidocaine in people with Cough, run by GlaxoSmithKline at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in oropharyngeal sensation (time frame: Dosing to 1 hour post dose). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2017; AzTrials last refreshed its copy on 8 Nov 2026.