CoughPhase 1NCT01587716
A Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK2339345.
A Phase 1 study testing GSK2339345 (Inhaled) Single Dose and GSK2339345 (Inhaled) Repeat Dose in people with Cough, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
This is a study of the sodium channel inhibitor, GSK2339345. Cohort 1 will assess the safety, tolerability and PK of single ascending doses of GSK2339345 administered via an aqueous droplet inhaler in healthy subjects. 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 (Inhaled) Single Dose and GSK2339345 (Inhaled) Repeat Dose
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 23 Apr 2012to 30 Jul 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
- ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Average QTcB < 450 msec
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. 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.
- 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 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 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).
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- Body weight ≥ 50 kg and BMI within the range 19 - 32.0 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- 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
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Current or chronic history of cardiovascular disease (e.g. hypertension, coronary heart disease, heart attack, angina, myocardial infarct, and stroke).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as:
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- 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.
- 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.
- Unable to refrain from the 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.
- FEV1 less than 80% of the predicted value prior to dosing.
- 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 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.
- Subjects who have asthma or a history of asthma.
- Breath CO levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Unable to refrain from 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.
- Subjects who are unable to use the inhaler satisfactorily.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Double-blind, Placebo Controlled, Inhaled Single Escalating and Repeat Dose Study Using an Aqueous Droplet Inhaler to Investigate the Safety, Tolerability and Pharmacokinetics of GSK2339345.
This is a study of the sodium channel inhibitor, GSK2339345. Cohort 1 will assess the safety, tolerability and PK of single ascending doses of GSK2339345 administered via an aqueous droplet inhaler in healthy subjects. Cohort 2 will assess the safety, tolerability, and PK of repeat doses of GSK2339345 administered four times a day for two consecutive days via an aqueous droplet inhaler.
Read the detailed description
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics (PK) 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 administered via an aqueous droplet inhaler. Cohort 1 is a randomised, double-blind, placebo-controlled, cross-over, inhaled single-dose escalating study using an aqueous droplet inhaler. Cohort 1 will include assessments of sensate changes via a 4 point scale, assessment of taste via an 11 point scale, and PK assessments to investigate the PK profile of GSK2339345. Cohort 2 of this study is a randomised, double blind, placebo controlled, parallel group, inhaled repeat dose study using a aqueous droplet inhaler. Subjects will be randomised to receive 2000 microgram of GSK2339345 or placebo four times a day for two consecutive study days. Similar assessments of sensations to those used in Cohort 1 will be performed. The potential for systemic cardiovascular (CV) or central nervous system (CNS) effects will also be assessed throughout the study via observation. Cohort 2 will also include PK assessments to investigate the PK profile of GSK2339345. Placebo will be used throughout the study as a control.
- Conditions
- Cough
- Being tested
- GSK2339345 (Inhaled) Single Dose, Placebo (Inhaled) Single Dose, GSK2339345 (Inhaled) Repeat Dose, Placebo (Inhaled) Repeat Dose
- Keywords
- Safety and tolerability, pharmacokinetics, cough, voltage gated sodium channels (VGSC), anaesthesia
- Medical subject headings
- Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2339345 (Inhaled) Single DoseDrug
250, 1000 and 2000 microgram (proposed doses)
Placebo (Inhaled) Single DoseOther
Inhaled 0.9% sodium chloride solution
GSK2339345 (Inhaled) Repeat DoseDrug
2000 microgram (proposed dose) administered 4 times a day for two consecutive days
Placebo (Inhaled) Repeat DoseOther
Inhaled 0.9% sodium cholride solution
| Study group | Role | What they receive |
|---|---|---|
| 1. Inhaled GSK2339345/Placebo Single Dose (Cohort 1) | Experimental | administered three ascending doses of GSK2339345 or placebo as a solution via an aqueous droplet inhaler over four treatment periods, with at least 5 days washout between doses Receives: Drug: GSK2339345 (Inhaled) Single Dose; Other: Placebo (Inhaled) Single Dose |
| 2. Inhaled GSK2339345/Placebo Repeat Dose (Cohort 2) | Experimental | administered a dose of GSK2339345 or placebo, four times a day on two consecutive days. Each subject will receive either GSK2339345 or matching placebo as a solution administered via an aqueous droplet inhaler Receives: Drug: GSK2339345 (Inhaled) Repeat Dose; Other: Placebo (Inhaled) Repeat Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology, clinical biochemistry and cardiac troponin.
To assess the safety and tolerability of single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler.
Measured: Approximately 5 weeks from first dose to the follow-up visit.
Assessment of oropharyngeal sensation perturbation via a 4 point scale.
To assess the changes in oropharyngeal sensation caused by single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler.
Measured: Approximately 5 weeks from first dose to the follow-up visit.
Secondary outcomes (2)
Plasma concentrations of GSK2339345 and single and repeat dose derived pharmacokinetic parameters including Cmax, tmax, AUC(0-t), AUC(0-inf), and AUC(0- τ), as appropriate where data allow.
To evaluate the systemic pharmacokinetics of single and repeat doses of inhaled GSK2339345 in healthy volunteers administered by an aqueous droplet inhaler.
Measured: Approximately 5 weeks from first dose to the follow-up visit.
Identification of taste of the solution and rating on 11 point scale to rate pleasantness or unpleasantness
To assess the palatability of GSK2339345 administered by an aqueous droplet inhaler
Measured: Approximately 5 weeks from first dose to the follow-up visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2012 (estimated)
- Study start23 Apr 2012
- Primary completion30 Jul 2012
- Study completion30 Jul 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 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
- NCT01587716
- Sponsor's protocol ID
- 115658
- Status last verified
- Jul 2017
- First submitted
- 19 Apr 2012
- Last updated
- 26 Jul 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 26 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo Controlled, Inhaled Single Escalating and Repeat Dose Study Using an Aqueous Droplet Inhaler to Investigate the Safety, Tolerability and Pharmacokinetics of GSK2339345.
- ClinicalTrials.gov ID
- NCT01587716
- Acronym / sponsor ID
- 115658
- Conditions
- Cough
- Keywords
- Safety and tolerability, pharmacokinetics, cough, voltage gated sodium channels (VGSC), anaesthesia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 23 Apr 2012 (actual)
- Primary completion
- 30 Jul 2012 (actual)
- Study completion
- 30 Jul 2012 (actual)
- First posted
- 30 Apr 2012 (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 study of the sodium channel inhibitor, GSK2339345. Cohort 1 will assess the safety, tolerability and PK of single ascending doses of GSK2339345 administered via an aqueous droplet inhaler in healthy subjects. Cohort 2 will assess the safety, tolerability, and PK of repeat doses of GSK2339345 administered four times a day for two consecutive days via an aqueous droplet inhaler.
Detailed description
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics (PK) 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 administered via an aqueous droplet inhaler. Cohort 1 is a randomised, double-blind, placebo-controlled, cross-over, inhaled single-dose escalating study using an aqueous droplet inhaler. Cohort 1 will include assessments of sensate changes via a 4 point scale, assessment of taste via an 11 point scale, and PK assessments to investigate the PK profile of GSK2339345. Cohort 2 of this study is a randomised, double blind, placebo controlled, parallel group, inhaled repeat dose study using a aqueous droplet inhaler. Subjects will be randomised to receive 2000 microgram of GSK2339345 or placebo four times a day for two consecutive study days. Similar assessments of sensations to those used in Cohort 1 will be performed. The potential for systemic cardiovascular (CV) or central nervous system (CNS) effects will also be assessed throughout the study via observation. Cohort 2 will also include PK assessments to investigate the PK profile of GSK2339345. Placebo will be used throughout the study as a control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1. Inhaled GSK2339345/Placebo Single Dose (Cohort 1) | Experimental | Drug: GSK2339345 (Inhaled) Single Dose, Other: Placebo (Inhaled) Single Doseadministered three ascending doses of GSK2339345 or placebo as a solution via an aqueous droplet inhaler over four treatment periods, with at least 5 days washout between doses |
| 2. Inhaled GSK2339345/Placebo Repeat Dose (Cohort 2) | Experimental | Drug: GSK2339345 (Inhaled) Repeat Dose, Other: Placebo (Inhaled) Repeat Doseadministered a dose of GSK2339345 or placebo, four times a day on two consecutive days. Each subject will receive either GSK2339345 or matching placebo as a solution administered via an aqueous droplet inhaler |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Average QTcB < 450 msec
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. 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.
- 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 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 the follow up visit.
Key exclusion criteria (20 listed)
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Current or chronic history of cardiovascular disease (e.g. hypertension, coronary heart disease, heart attack, angina, myocardial infarct, and stroke).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
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 (Inhaled) Single Dose250, 1000 and 2000 microgram (proposed doses) | Drug | 1. Inhaled GSK2339345/Placebo Single Dose (Cohort 1) |
| Placebo (Inhaled) Single DoseInhaled 0.9% sodium chloride solution | Other | 1. Inhaled GSK2339345/Placebo Single Dose (Cohort 1) |
| GSK2339345 (Inhaled) Repeat Dose2000 microgram (proposed dose) administered 4 times a day for two consecutive days | Drug | 2. Inhaled GSK2339345/Placebo Repeat Dose (Cohort 2) |
| Placebo (Inhaled) Repeat DoseInhaled 0.9% sodium cholride solution | Other | 2. Inhaled GSK2339345/Placebo Repeat Dose (Cohort 2) |
Primary outcome
Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology, clinical biochemistry and cardiac troponin.
Time frame: Approximately 5 weeks from first dose to the follow-up visit.
To assess the safety and tolerability of single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler.
Assessment of oropharyngeal sensation perturbation via a 4 point scale.
Time frame: Approximately 5 weeks from first dose to the follow-up visit.
To assess the changes in oropharyngeal sensation caused by single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler.
2 secondary outcomes
Plasma concentrations of GSK2339345 and single and repeat dose derived pharmacokinetic parameters including Cmax, tmax, AUC(0-t), AUC(0-inf), and AUC(0- τ), as appropriate where data allow.
Time frame: Approximately 5 weeks from first dose to the follow-up visit.
Identification of taste of the solution and rating on 11 point scale to rate pleasantness or unpleasantness
Time frame: Approximately 5 weeks from first dose to the follow-up visit.
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 26 Jul 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 115658 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 (Inhaled) Single Dose and GSK2339345 (Inhaled) Repeat Dose 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 26 Jul 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?
Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology, clinical biochemistry and cardiac troponin. (time frame: Approximately 5 weeks from first dose to the follow-up visit.). The study lists 2 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 26 Jul 2017.