Study To Evaluate Safety And Tolerability Of GSK256066 In Chronic Obstructive Pulmonary Disease (COPD) Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00549679
First received: October 24, 2007
Last updated: October 25, 2012
Last verified: October 2012
  Purpose

This study will evaluate the safety and tolerability of the cfor the first time in mild to moderate COPD patients.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: GSK256066
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety and Tolerability of Inhaled GSK256066 in Mild to Moderate COPD Patients

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety Parameters: Adverse events, 12 Lead Electrocardiogram, Vital Signs, Clinical Laboratory Evaluations, [ Time Frame: after 28 days repeat dosing ]
  • Lung Function Parameters, Holter monitoring, Withdrawals for exacerbations of COPD. [ Time Frame: 28 days ]

Secondary Outcome Measures:
  • Plasma concentrations of GSK256066 and active metabolite GSK614917 and derived pharmacokinetic parameters [ Time Frame: 28 days ]
  • Parameters measured in induced sputum: Total cell number (cells/mL); Neutrophils, macrophages, lymphocytes and eosinophils as a percentage of total cells; Absolute numbers of neutrophils, macrophages, lymphocytes and eosinophils [ Time Frame: 28 days ]
  • The concentration of total protein and inflammatory biomarkers in induced sputum supernatant [ Time Frame: 28 days ]
  • Change from baseline in messenger ribonucleic acid (mRNA) and/or protein in induced sputum of established and exploratory markers of inflammation and established and exploratory pharmacodynamic markers [ Time Frame: 28 days ]
  • Lung function parameters (pre and post-bronchodilator) [ Time Frame: 28 days ]
  • Spirometry measures: FEV1, FVC Plethysmography measures Impulse oscillometry The concentration of serum inflammatory biomarkers [ Time Frame: 28 days ]
  • Lung Function Parameters Holter monitoring Withdrawals for exacerbations of COPD [ Time Frame: 28 days ]

Enrollment: 104
Study Start Date: October 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 25 mcg
25 microgram inhaled once daily
Drug: GSK256066
PDE4 inhibitor
Other Name: GSK256066
Experimental: 87.5 mcg
87.5 microgram inhaled once daily
Drug: GSK256066
PDE4 inhibitor
Other Name: GSK256066
Placebo Comparator: Placebo
Placebo inhaled once daily
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male adults or female adults of non-childbearing potential who are between 40 and 75 years of age (inclusive).
  • Subjects with a clinical diagnosis of COPD in accordance with the European Respiratory Society Consensus Statement and subjects categorised with moderate COPD as defined by the GOLD guidelines of 2006 [GOLD, 2006]
  • Subjects with a cigarette smoking history of ≥ 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or the equivalent). Both current and former smokers are eligible to be enrolled. A former smoker is defined as a subject who has not smoked for ≥6 months at Visit 1.
  • Subjects with a post-bronchodilator FEV1 to FVC ratio (FEV1/FVC) < 0.7 at Visit 1. Subjects will be assessed 30 (± 5) minutes after receiving salbutamol 400 μg.
  • Subjects with a post-bronchodilator FEV1 ≥ 50% and < 80% of predicted normal for height, age and sex at Visit 1. Subjects will be assessed 30 (± 5) minutes after receiving salbutamol 400 μg.
  • Subjects with a normal echocardiogram at screening, as defined by the absence of clinically significant wall motion, chamber size or valvular abnormalities
  • The subject must be capable of giving informed consent and can comply with the study requirements and timetable.

Exclusion Criteria:

  • Women who are pre-menopausal and of child-bearing potential.
  • Subjects weighing less than 50 kilograms (kg).
  • Subjects who are obese defined as having a body mass index (BMI) > 30.
  • Subjects with a current diagnosis of asthma.
  • Subjects who have required hospitalisation or treatment with oral corticosteroids and/or antibiotic therapy for acute worsening of COPD or lower respiratory tract infection in the 6 weeks prior to Screening.
  • Subjects who have received treatment with oral, intravenous, topical or intra-articular corticosteroids within 6 weeks of Screening or thereafter
  • Subjects with active tuberculosis, sarcoidosis or clinically overt bronchiectasis.
  • Subjects with a history of any type of malignancy with the exception of successfully treated squamous cell cancer of the skin.
  • Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with chronic inflammation (e.g. Inflammatory Bowel Disease).
  • Subjects with chronic infections (lasting longer than 6 months) such as gingivitis, periodontitis, prostatitis, gastritis, and urinary tract infections.
  • Subjects with any acute infection, sinus symptoms, or significant trauma (burns, fractures).
  • Subjects with clinically significant renal disease, diabetes mellitus/metabolic syndrome, hypertension or any other clinically significant cardiovascular, neurological, endocrine, or haematological abnormalities that are uncontrolled on permitted therapy.
  • Subjects who have participated in any GSK study/studies involving administration of COA.
  • The subject has a screening ECG parameters outside of ranges specified in protocol.
  • Subjects with hypoxaemia
  • Risk factors for human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection at Screening (Visit 1).
  • Subjects who have undergone surgery including lung volume reduction surgery in the last six months or have conditions that prevent them from performing spirometry.
  • Subjects with a history (or suspected history) of alcohol misuse or any other recreational substance abuse.
  • Subjects who require treatment with any of the following from the start of the run-in period (Day -14) until the end of the treatment phase:
  • Inhaled corticosteroids
  • Inhaled cromolyn sodium or nedocromil
  • Xanthines (theophylline preparations).
  • Leukotriene modifiers
  • Tiotropium
  • Long-acting inhaled beta2-agonists (salmeterol, formoterol)
  • Oral beta2-agonists
  • Subjects who are unable to abstain from other courses of medication during the run in phase including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines, anti-rhinitis or hay fever medication, other than short acting inhaled beta-agonists, ipratropium bromide and paracetamol (up to 4 g per day) for the treatment of minor ailments (eg headache) from 48h before the first dose until the follow-up visit. Subjects requiring medication between dosing and follow up may be excluded at the principal investigators discretion.
  • Subjects with any known hypersensitivity to salbutamol or ipratropium bromide.
  • Subjects who are participating or plan to participate in the active phase of a pulmonary rehabilitation programme during the study.
  • Subjects who have received an investigational drug within 30 days or within five drug half-lives of the investigational drug (whichever is longer).
  • Subjects with any clinically relevant abnormality detected by the assessments at Screening.
  • Subjects who have experienced an exacerbation during the run-in period requiring treatment with oral corticosteroids and/or macrolide antibiotics and/or hospitalisation.
  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: NCT00549679

Locations
Estonia
GSK Investigational Site
Tallinn, Estonia, 13419
Finland
GSK Investigational Site
Tampere, Finland, 33520
Germany
GSK Investigational Site
Gauting, Bayern, Germany, 82131
GSK Investigational Site
Berlin, Germany, 10717
GSK Investigational Site
Hamburg, Germany, 22291
Netherlands
GSK Investigational Site
Hoorn, Netherlands, 1624 NP
GSK Investigational Site
Horn, Netherlands, 6085 NM
GSK Investigational Site
Veldhoven, Netherlands, 5504 DB
Russian Federation
GSK Investigational Site
Barnaul, Russian Federation, 656 045
GSK Investigational Site
Moscow, Russian Federation, 105 077
GSK Investigational Site
St. Petersburg, Russian Federation, 197022
GSK Investigational Site
Yaroslavl, Russian Federation, 150003
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00549679     History of Changes
Other Study ID Numbers: IPC101939
Study First Received: October 24, 2007
Last Updated: October 25, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by GlaxoSmithKline:
Chronic Obstructive Pulmonary Disease (COPD)
COPD
Repeat Dose
GSK256066

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Chronic Disease
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on October 19, 2014