Last updated: 11/07/2018 09:30:56
The safety, tolerability, PK and PD of GSK2339345 in healthy subjectsFTIH
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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.
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Change in oropharyngeal sensation
Timeframe: Dosing to 1 hour post dose
Adverse events (AEs) for all study participants
Timeframe: Dosing to 24 hours post dose
Assessment of vital signs for all study participants
Timeframe: Screening to follow-up
Holter ECG measurement for all study participants
Timeframe: Screening (Part A and Part B)
12-lead ECG measurements for all study participants
Timeframe: Screening to follow-up
Body temperature for all study participants
Timeframe: 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
Timeframe: 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
Timeframe: Part B only: Screening, pre-dose and 24 hours post dose on Day 1
Secondary outcomes:
Palatability by identification of solution taste and 11 point scale
Timeframe: 30 minutes post dose
Systemic pharmacokinetics of GSK2339345 using plasma concentrations of GSK2339345 and derived pharmacokinetic parameters
Timeframe: Pre-dose to 24 hours post dose
Effect of an inhaled nebulised dose of GSK2339345 on cough response to capsaicin challenge in healthy volunteers
Timeframe: Part B: Day 2, 10 minutes post dose
Interventions:
Enrollment:
31
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)
October 2011 to March 2012
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- 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.
- 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).
Inclusion and exclusion criteria
Inclusion criteria:
- 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).
- 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.
Exclusion criteria:
- 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).
- 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 location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
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
2012-15-03
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.
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