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

October 24, 2007
October 25, 2012
October 2007
December 2008   (final data collection date for primary outcome measure)
  • 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 ]
safety and tolerability [ Time Frame: after 28 days repeat dosing ]
Complete list of historical versions of study NCT00549679 on ClinicalTrials.gov Archive Site
  • 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 ]
  • pharmacokinetics of GSK256066 in patients with mild to moderate COPD [ Time Frame: over 28 days ]
  • the effect of treatment on exploratory markers of inflammation and PDE4 activity in induced sputum [ Time Frame: 28 days ]
  • pulmonary function [ Time Frame: over 28 days ]
Not Provided
Not Provided
 
Study To Evaluate Safety And Tolerability Of GSK256066 In Chronic Obstructive Pulmonary Disease (COPD) Patients
A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety and Tolerability of Inhaled GSK256066 in Mild to Moderate COPD Patients

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

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Pulmonary Disease, Chronic Obstructive
  • Drug: GSK256066
    PDE4 inhibitor
    Other Name: GSK256066
  • Drug: Placebo
    Placebo
  • Experimental: 25 mcg
    25 microgram inhaled once daily
    Intervention: Drug: GSK256066
  • Experimental: 87.5 mcg
    87.5 microgram inhaled once daily
    Intervention: Drug: GSK256066
  • Placebo Comparator: Placebo
    Placebo inhaled once daily
    Intervention: Drug: Placebo
Watz H, Mistry SJ, Lazaar AL; IPC101939 investigators. Safety and tolerability of the inhaled phosphodiesterase 4 inhibitor GSK256066 in moderate COPD. Pulm Pharmacol Ther. 2013 Oct;26(5):588-95. doi: 10.1016/j.pupt.2013.05.004. Epub 2013 May 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
104
December 2008
December 2008   (final data collection date for primary outcome measure)

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.
Both
40 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Estonia,   Finland,   Germany,   Netherlands,   Russian Federation
 
NCT00549679
IPC101939
No
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP