A Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK2339345.

NCT01587716 | Completed Phase 1

• 1 other identifier: 115658
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Cough

Keywords

Safety and tolerability, pharmacokinetics, cough, voltage gated sodium channels (VGSC), anaesthesia

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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.

  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

  Approximately 5 weeks from first dose to the follow-up visit.

Study Arms (2)

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

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

Drug: GSK2339345 (Inhaled) Repeat Dose; Other: Placebo (Inhaled) Repeat Dose

Interventions

GSK2339345 (Inhaled) Single Dose DRUG

250, 1000 and 2000 microgram (proposed doses)

1. Inhaled GSK2339345/Placebo Single Dose (Cohort 1)

Placebo (Inhaled) Single Dose OTHER

Inhaled 0.9% sodium chloride solution

1. Inhaled GSK2339345/Placebo Single Dose (Cohort 1)

GSK2339345 (Inhaled) Repeat Dose DRUG

2000 microgram (proposed dose) administered 4 times a day for two consecutive days

2. Inhaled GSK2339345/Placebo Repeat Dose (Cohort 2)

Placebo (Inhaled) Repeat Dose OTHER

Inhaled 0.9% sodium cholride solution

2. Inhaled GSK2339345/Placebo Repeat Dose (Cohort 2)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, 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.
• Results for study 115658 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Cough

Interventions

Inhalation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2012
• First Posted: April 30, 2012
• Study Start: April 23, 2012
• Primary Completion: July 30, 2012
• Study Completion: July 30, 2012
• Last Updated: July 26, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)