Last updated: 11/07/2018 09:45:24
A study to investigate the safety, tolerability and pharmacokinetics of GSK2339345.
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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.
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology, clinical biochemistry and cardiac troponin.
Timeframe: Approximately 5 weeks from first dose to the follow-up visit.
Assessment of oropharyngeal sensation perturbation via a 4 point scale.
Timeframe: Approximately 5 weeks from first dose to the follow-up visit.
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.
Timeframe: 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
Timeframe: Approximately 5 weeks from first dose to the follow-up visit.
Interventions:
Enrollment:
36
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
J Marks-Konczalik, R Murdoch, K Kelly, A Cheesbrough, S Siederer, Dave Singh, J Smith. Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK2339345 – novel sodium channel blocker. Results from two phase I studies in Healthy Volunteers. ATS (2014) American Thoracic Society - 110th International Conference
Medical condition
Cough
Product
GSK2339345
Collaborators
Not applicable
Study date(s)
April 2012 to July 2012
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is
- acceptable if bilirubin is fractionated and direct bilirubin <35%).
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
- result within 3 months of screening
Inclusion and exclusion criteria
Inclusion criteria:
- 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).
- 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.
Exclusion criteria:
- 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.
- 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.
History of regular alcohol consumption within 6 months of the study defined as:
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2012-30-07
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Participate in clinical trial
Additional information
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Click hereResults for study 115658 can be found on the GSK Clinical Study Register.
Click hereAccess to clinical trial data by researchers
Visit website