The Safety, Tolerability, PK and PD of GSK2339345 in Healthy Subjects

NCT01494636 | Completed Phase 1

• 1 other identifier: 115419
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cough

Keywords

Capsaicin Challenge; Pharmacodynamics; Safety; Pharmacokinetics; Oral GSK2339345; Tolerability; FTIH; Chronic Cough

Outcome Measures

Primary Outcomes (8)

• 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

  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

  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

  Screening to follow-up

• Holter ECG measurement for all study participants

  24 hour Holter ECG will be taken at screening

  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

  Screening to follow-up

• Body temperature for all study participants

  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

  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

  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

  30 minutes post dose

• Systemic pharmacokinetics of GSK2339345 using plasma concentrations of GSK2339345 and derived pharmacokinetic parameters

  Pre-dose to 24 hours post dose

• Effect of an inhaled nebulised dose of GSK2339345 on cough response to capsaicin challenge in healthy volunteers

  Part B: Day 2, 10 minutes post dose

Study Arms (2)

GSK2339345 (solution) (part A)

EXPERIMENTAL

Part A

Drug: GSK2339345 (solution)

GSK2339345/ Placebo/ Lidocaine (nebulised) (part B)

EXPERIMENTAL

Part B

Drug: GSK2339345 (nebulised); Drug: Placebo (0.9% sodium chloride solution); Drug: Lidocaine

Interventions

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 (solution) (part A)

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.

GSK2339345/ Placebo/ Lidocaine (nebulised) (part B)

Placebo (0.9% sodium chloride solution) DRUG

Administered on Day 1 of one of the treatment periods in part B. Randomised. Nebulised.

GSK2339345/ Placebo/ Lidocaine (nebulised) (part B)

Lidocaine DRUG

40mg dose. Administered on Day 2 of one of the treatment periods in part B. Randomised. Nebulised.

GSK2339345/ Placebo/ Lidocaine (nebulised) (part B)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Manchester, M23 9QZ, 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 115419 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Cough; Chronic Cough

Interventions

Solutions; Sodium Chloride; Lidocaine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2011
• First Posted: December 19, 2011
• Study Start: October 17, 2011
• Primary Completion: March 15, 2012
• Study Completion: March 15, 2012
• Last Updated: June 20, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)