Study to Investigate Safety, Tolerability, Pharmacokinetics & Pharmacodynamics of Single & Repeat Doses of GSK2269557

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01462617
First received: October 6, 2011
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

The study will comprise three Parts:

Part A will consist of two cohorts of healthy male volunteers to assess the safety, tolerability and pharmacokinetics of ascending single doses of nebulised GSK2269557. Blinded safety and available PK data will be reviewed before each dose escalation.

Part B will be one cohort to examine the safety, tolerability and pharmacokinetics of a repeated dose of GSK2269557 given by nebuliser for 7 days in healthy male volunteers. The total daily dose will be the same as, or lower than, doses that are well tolerated in Part A.

Part C will consist of two cohorts of single nebulised doses in healthy male smokers, to assess pharmacodynamic endpoints in sputum and bronchoalveolar lavage.


Condition Intervention Phase
Asthma
Drug: GSK2269557
Drug: GSK2269557 matching placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Single-centre. Double-blind, Placebo Controlled Three Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Single and Repeat Doses of Nebulised GSK2269557 in Healthy Male Subjects

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • clinical monitoring of blood pressure and pulse rate [ Time Frame: Day 1 until Day 8 ] [ Designated as safety issue: Yes ]
  • clinical monitoring of cardiac parameters [ Time Frame: Day 1 until Day 8 ] [ Designated as safety issue: Yes ]
  • clinical monitoring of lung function [ Time Frame: Day 1 until Day 8 ] [ Designated as safety issue: Yes ]
  • clinical monitoring of safety laboratory data [ Time Frame: Day 1 until Day 8 ] [ Designated as safety issue: Yes ]
  • clinical monitoring of adverse events [ Time Frame: Day 1 until Day 8 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics profile at predose, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 hours post-dose. Profile to include Cmas, Area Under the Curve, Tmax [ Time Frame: Day 1 to Day 8 ] [ Designated as safety issue: No ]
  • PD bimoarkers potentially to incldue PIP3, Akt, S6K, IFNy, IgE, CD62L and CD44. [ Time Frame: Day 1 to Day 8 ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: July 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pi3K
Experimental
Drug: GSK2269557
Study Drug
Placebo Comparator: Placebo
Placebo Comparator
Drug: GSK2269557 matching placebo
Study Drug

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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 at the Investigator's discretion provided the abnormality will not jeopardize subject safety or study integrity .
  • Male between 18 and 55 years of age inclusive, at the time of signing the informed consent.
  • 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.
  • Body weight greater than or equal to 55kg and BMI within the range 18-31 kg/m2 (inclusive).
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Average QTcB < 450 msec
  • AST and ALT < 2xULN; alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

Additional inclusion criteria for healthy smokers Cohorts 4-5 (Part C)

  • Subjects who are current smokers. Must have smoked in the 12-month period preceding the screening visit and have a pack history of greater than or equal to 5 pack years. [number of pack years = (number of cigarettes per day/20) x number of years smoked].
  • Normal spirometry (FEV1 greater than or equal to 80% of predicted, FEV1/FVC ratio greater than or equal to 70%) at screening. Predictions should be according to ECCS equations

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).
  • A history of congestive heart failure, coronary insufficiency or cardiac arrhythmia or a finding on screening 24h Holter monitor that would contraindicate the subject's participation in the study.
  • 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: 90 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, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • The subject has received any type of vaccination within 3 weeks of their first dose of investigational product, or are expected to be vaccinated within 3 weeks after their last dose of investigational product.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy (including atopic asthma) 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 90 day period.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Subjects who have asthma or a history of asthma.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01462617

Locations
United Kingdom
GSK Investigational Site
London, United Kingdom, SE1 1YR
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01462617     History of Changes
Other Study ID Numbers: 115117
Study First Received: October 6, 2011
Last Updated: May 29, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

ClinicalTrials.gov processed this record on October 29, 2014