Pulmonary Disease, Chronic ObstructivePhase 2NCT00549679
Study To Evaluate Safety And Tolerability Of GSK256066 In Chronic Obstructive Pulmonary Disease (COPD) Patients
A Phase 2 study testing GSK256066 in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 15 sites in 6 countries.
Trial summary
This study will evaluate the safety and tolerability of the cfor the first time in mild to moderate COPD patients. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- GSK256066
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 15 sitesin 6 countries
- Study dates
- 4 Oct 2007to 15 Dec 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 32Show fewer
- 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.
Trial locations and contacts
15 sites in 6 countries.
15 sites in 6 countries
Russia4 sites
GSK Investigational Site
Barnaul, 656 045
GSK Investigational Site
Moscow, 105 077
GSK Investigational Site
Saint Petersburg, 197022
GSK Investigational Site
Yaroslavl, 150003
Germany3 sites
GSK Investigational Site
Berlin, 10717
GSK Investigational Site
Gauting, Bavaria, 82131
GSK Investigational Site
Hamburg, 22291
Netherlands3 sites
GSK Investigational Site
Hoorn, 1624 NP
GSK Investigational Site
Horn, 6085 NM
GSK Investigational Site
Veldhoven, 5504 DB
Slovakia3 sites
GSK Investigational Site
Bratislava, 826 06
GSK Investigational Site
Košice, 041 90
GSK Investigational Site
Martin, 036 59
About this study
Official title: 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.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- GSK256066, Placebo
- Keywords
- Chronic Obstructive Pulmonary Disease (COPD), COPD, Repeat Dose, GSK256066
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK256066Drug
PDE4 inhibitor
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 25 mcg | Experimental | 25 microgram inhaled once daily Receives: Drug: GSK256066 |
| 87.5 mcg | Experimental | 87.5 microgram inhaled once daily Receives: Drug: GSK256066 |
| Placebo | Placebo comparator | Placebo inhaled once daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention.
Measured: Up to follow up (approximately 56 days)
Change from Baseline (Day 0 [pre-bronchodilator]) in 12-lead electrocardiogram (ECG) findings
ECG parameters consist of QT interval corrected by Bazett's (QTcB) and Fridericia's (QTcF) formulas, QT interval, QRS duration and PR interval. Baseline was defined as value at Day 0 (pre-bronchodilator). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was the mean of the 3 pre-salbutamol measurements at Day 0. It was assessed on Baseline, Day 1, 7, 14, 15, 21, 27 and 28. Post Baseline, ECG was performed 1-2 hours post dose.
Measured: Baseline (Day 0 [pre-bronchodilator]) and up to Day 28 (Visit 6b)
Change from Baseline (Day 0 [pre-bronchodilator]) in 12-lead electrocardiogram (ECG) findings-ventricular rate
ECG parameters consist of ventricular rate. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was the mean of the 3 pre-salbutamol measurements at Day 0. It was as/sessed on Baseline, Day 1, 7, 14, 15, 21, 27 and 28. Post Baseline, ECG was performed 1-2 hours post dose.
Measured: Baseline (Day 0 [pre-bronchodilator]) and up to Day 28 (Visit 6b)
Number of participants with abnormal (potential clinical importance [PCI]) systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR)
The PCI range for SBP was < 85 and > 160 millimeters of mercury (mmHg), DBP was < 45 and > 100 mmHg and for HR < 40 and > 110 beats per minute. It was assessed on Baseline (pre-bronchodilator), Day 14 and 27. Data for SBP high, SBP low, DBP high, DBP low, HR high and HR low is presented.
Measured: Up to Day 27 (Visit 6a)
Number of participants with abnormal (PCI) clinical chemistry
Clinical chemistry included: albumin, bicarbonate, alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), blood urea, creatinine, magnesium, sodium, potassium, chloride, glucose, total bilirubin, direct bilirubin, indirect bilirubin, total protein, gamma glutamyltransferase (GGT), calcium, creatinine kinase, creatine kinase-MB, creatinine clearance (estimated; male and female), lactate dehydragenase, and troponin, triglycerides. Data for abnormal parameters (above and below range) is provided. It was assessed on Baseline (Day -3), Day 14, 28 and on follow up visit (Day 42). Data for only abnormal observations is presented.
Measured: Up to Day 42 (follow up visit)
Number of participants with abnormal (PCI) hematology
Hematology included: haemoglobin, haematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell (RBC) indices, white blood cell (WBC), basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. Data for abnormal parameters (above and below range) is provided. It was assessed on Baseline (Day -3), Day 14, 28 and on follow up visit (Day 42). Data for only abnormal observations is presented.
Measured: Up to Day 42 (follow up visit)
Number of participants with abnormal urinalysis
Abnormal urinalysis data for RBC in urine and haematuria presented. Data for abnormal parameters (above and below range) is provided. It was assessed on Baseline (Day -3), Day 7, 14, 21, 28 and on follow up visit (Day 42). Data for only abnormal observations is presented.
Measured: Up to Day 56 (Visit follow up)
Change from Baseline (Day 0) in lung function parameters: forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)
The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline value defined as the value on Day 0. It was assessed on Baseline (Day 0), Day 14 and 27. Spirometry tests was performed before and 30 minutes after dosing with salbutamol (bronchodilator) on Day 0 and before dosing with GSK256066. As they were analyzed separately, there were two Baselines for these tests, 'pre bronchodilator Baseline' and 'post bronchodilator Baseline'. Smoking and short acting bronchodilators were avoided 6 hour prior to administration of the salbutamol. Observations with best test review (BTR) grading of 'not acceptable' were excluded.
Measured: Baseline (Day 0) and up to Day 27 (Visit 6a)
Number of participants with abnormal Holter interpretations
Holter parameters were derived by visit over the 24 hour period as: maximum HR over 24 hours was the maximum HR of all time slices and mean HR over 24 hours was the mean HR of all time slices, weighted by the time length of each slice. The total number of ventricular runs and the number of supraventricular runs over 24 hours were derived by summing each count across all time slices. Data for normal, abnormal: not clinically significant and abnormal: clinically significant is presented. It was assessed on Baseline (Day 0), Day 14and 27. Data for normal, abnormal: clinically significant and abnormal: clinically not significant presented.
Measured: Up to Day 27 (Visit 6a)
Number of participants who withdrawn for exacerbations of chronic obstructive pulmonary disease (COPD)
An exacerbation of COPD was defined as worsening of COPD symptoms requiring changes to normal treatment including antimicrobial therapy, short courses of oral steroids and other bronchodilator therapy. If clinically indicated, short-term treatment with antibiotics could be prescribed for the exacerbation. Any participants requiring treatment with inhaled or oral corticosteroids or admission to hospital were withdrawn from the study.
Measured: Up to Day 27 (Visit 6a)
Secondary outcomes (23)
Plasma concentrations of GSK256066 and active metabolite GSK614917 and derived pharmacokinetic parameters: area under the plasma drug concentration versus time curve (AUC0-last)
AUC0-last determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. AUC0-last for GSK256066 is presented. As GSK614917 concentrations were generally non-quantifiable, no summary statistics were derived for GSK614917 pharmacokinetic parameters due to the large number of missing values resulting from non-quantifiable concentration-time data. AUC(0-t) imputed with half lowest observed AUC(0-t) (half of 1.28 hour×picogram/ milliliters [mL]).
Measured: Pre-dose and at 15, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hour post dosing at Baseline (Visit 2a) and Days 14 and 27 (Visits 4a and 6a)
Plasma concentrations of GSK256066 and active metabolite GSK614917 and derived pharmacokinetic parameters: maximum observed plasma drug concentration (Cmax)
The first occurrence of the maximum observed concentration determined directly from the raw concentration-time data. Cmax for GSK256066 is presented. As GSK614917 concentrations were generally non-quantifiable, no summary statistics were derived for GSK614917 pharmacokinetic parameters due to the large number of missing values resulting from non-quantifiable concentration-time data. One pre-dose GSK614917 concentration at the Baseline visit which was >5% of the corresponding Cmax was excluded from the pharmacokinetic analysis. Cmax imputed with half lower limit of quantification (LLQ; half of 5 picogram/mL).
Measured: Pre-dose and at 15, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hour post dosing at Baseline (Visit 2a) and Days 14 and 27 (Visits 4a and 6a)
Plasma concentrations of GSK256066 and GSK614917 and derived pharmacokinetic parameters: time to maximum observed plasma drug concentration (tmax)
The tmax was the time at which Cmax was observed. Tmax was determined directly from the raw concentration-time data. Pharmacokinetic data of GSK256066 is presented. As GSK614917 concentrations were generally non-quantifiable, no summary statistics were derived for GSK614917 pharmacokinetic parameters due to the large number of missing values resulting from non-quantifiable concentration-time data.
Measured: Pre-dose and at 15, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hour post dosing at Baseline (Visit 2a) and Days 14 and 27 (Visits 4a and 6a)
Change from Baseline (Day -3) total cell number (cells/mL) in induced sputum
Sputum was performed using ipratropium bromide. Participants must fast for 2 hour prior to the sputum induction (only water was allowed) and on Day 28 (Visit 6b), it was performed 2-4 hours after the final dose of study medication. One participant had a total number of neutrophil cell/ mLs count of 0 which was imputed to 1. Data for adjusted geometric means of macrophages, neutrophils cells per mLs and total leukocyte count is presented as geometric mean. The change from Baseline was calculated by subtracting the Baseline values from the Day 28 values. Baseline was defined as the value at Day -3. Total number of cells per mL was calculated by percentage of cells divided by 100 multiplied by total leukocyte count. It was assessed on Baseline and Day 28.
Measured: Baseline (Day -3) and Day 28 (Visit 6b)
Change from Baseline (Day -3) in neutrophils and macrophages as a percentage of total cells in induced sputum
Sputum was performed using ipratropium bromide. Participants must fast for 2 hour prior to the sputum induction (only water was allowed) and on Day 28 (Visit 6b), it was performed 2-4 hours after the final dose of study medication. One participant had a total number of neutrophil cell/ mLs count of 0 which was imputed to 1. Data for adjusted means of percentage of total cells macrophages and neutrophils is presented as least square mean. The change from Baseline was calculated by subtracting the Baseline values from the Day 28 values. Baseline was defined as the value at Day -3. Percentage cells was calculated by absolute cell count divided by total non squamous cell count multiplied by 100. It was assessed on Baseline and Day 28.
Measured: Baseline (Day -3) and Day 28 (Visit 6b)
Summary of mean lymphocytes, bronchial epithelial cells and eosinophils as a percentage of total cells in induced sputum
Sputum was performed using ipratropium bromide. Participants must fast for 2 hour prior to the sputum induction (only water was allowed) and on Day 28 (Visit 6b), it was performed 2-4 hours after the final dose of study medication. Data for adjusted means of percentage of total cells macrophages and neutrophils is presented as geometric mean. The change from Baseline was calculated by subtracting the Baseline values from the Day 28 values. Baseline was defined as the value at Day -3. Percentage cells was calculated by absolute cell count divided by total non squamous cell count multiplied by 100. It was assessed on Baseline and Day 28.
Measured: Up to Day 28 (Visit 6b)
Absolute numbers of leukocytes, neutrophils and macrophages in induced sputum
Sputum was performed using ipratropium bromide. Participants must fast for 2 hour prior to the sputum induction (only water was allowed) and on Day 28 (Visit 6b), it was performed 2-4 hours after the final dose of study medication. One participant had a total number of neutrophil cell/ mLs count of 0 which was imputed to 1. Total number of cells per mL was calculated by percentage of cells divided by 100 multiplied by total leukocyte count. It was assessed on Baseline and Day 28. One participant had a total number of neutrophil cell/ mLs count of 0 which was imputed to 1.
Measured: Up to Day 28 (Visit 6b)
Absolute numbers of bronchial epithelial cells, lymphocytes and eosinophils in induced sputum
Sputum was performed using ipratropium bromide. Participants must fast for 2 hour prior to the sputum induction (only water was allowed) and on Day 28 (Visit 6b), it was performed 2-4 hours after the final dose of study medication. One participant had a total number of neutrophil cell/ mL count of 0 which was imputed to 1. Total number of cells per mL was calculated by percentage of cells divided by 100 multiplied by total leukocyte count. It was assessed on Baseline and Day 28.
Measured: Up to Day 28 (Visit 6b)
Summary of concentration of total protein in induced sputum supernatant
Sputum was performed using ipratropium bromide. Participants must fast for 2 hour prior to the sputum induction (only water was allowed) and on Day 28 (Visit 6b), it was performed 2-4 hours after the final dose of study medication. It was assessed on Baseline and Day 28. Values below LLQ or above upper limit of quantification (ULQ) was imputed to half the LLQ or ULQ, LLQs: total protein: 62.5 µg/mL and ULQ: total protein: 400 µg/mL. Adjusted mean values for current smokers and former smokers is presented as least square mean.
Measured: Up to Day 28 (Visit 6b)
The concentration of inflammatory biomarkers in induced sputum supernatant: interleukin (IL) 8
Sputum was performed using ipratropium bromide. Participants must fast for 2 hour prior to the sputum induction (only water was allowed) and on Day 28 (Visit 6b), it was performed 2-4 hours after the final dose of study medication. It was assessed on Baseline and Day 28. Values below LLQ or above ULQ was imputed to half the LLQ or ULQ, LLQs: IL8: 70000 picograms/mL and ULQ: IL8: 360000 picograms/mL.
Measured: Up to Day 28 (Visit 6b)
The concentration of inflammatory biomarkers in induced sputum supernatant: myeloperoxidase (MPO)
Sputum was performed using ipratropium bromide. Participants must fast for 2 hour prior to the sputum induction (only water was allowed) and on Day 28 (Visit 6b), it was performed 2-4 hours after the final dose of study medication. It was assessed on Baseline and Day 28. Values below LLQ or above ULQ was imputed to half the LLQ or ULQ, LLQs: MPO: 90 nanograms/mL and ULQ: IL8: 5000 nanograms/mL.
Measured: Up to Day 28 (Visit 6b)
Summary of messenger ribonucleic acid (mRNA) and/or protein in induced sputum of established and exploratory markers of inflammation: IL-6, IL-1 beta and IL-8
Sputum was performed using ipratropium bromide. Participants must fast for 2 hour prior to the sputum induction (only water was allowed) and on Day 28 (Visit 6b), it was performed 2-4 hours after the final dose of study medication. It was assessed on Baseline and Day 28. Data for adjusted mean is presented as least square mean.
Measured: Day 28 (Visit 6b)
Summary of mRNA and/or protein in induced sputum of established and exploratory pharmacodynamic markers: Phosphodiesterase-4 B (PDE4B), SNF1 like kinase (SNF1LK)
Sputum was performed using ipratropium bromide. Participants must fast for 2 hour prior to the sputum induction (only water was allowed) and on Day 28 (Visit 6b), it was performed 2-4 hours after the final dose of study medication. It was assessed on Baseline and Day 28.
Measured: Up to Day 28 (Visit 6b)
Summary of lung function parameters (pre and post-bronchodilator): mean spirometry measures FEV1 and FVC
Spirometry tests was performed before and 30 minutes after dosing with salbutamol (bronchodilator) on Day 0 and before dosing with GSK256066. As they were analyzed separately, there were two Baselines for these tests, 'pre bronchodilator Baseline' and 'post bronchodilator Baseline'. Smoking and short acting bronchodilators were avoided 6 hour prior to administration of the salbutamol. It was assessed on Baseline (Day 0), Day 14 and 27. Observations with BTR grading of 'not acceptable' were excluded.
Measured: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): plethysmography measures: inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), slow vital capacity (SVC) and thoracic gas volume (TGV)
Plethysmography procedures was performed 30 minutes after dosing with salbutamol and prior to dosing with GSK256066. Participants were resting in the body box for at least 1 minute prior to any assessments. Smoking and short acting bronchodilators should be avoided 6 hour prior to administration of the salbutamol. It was assessed on Baseline (Day 0) and 27. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): plethysmography measures: plus airway resistance (Raw)
Plethysmography procedures was performed 30 minutes after dosing with salbutamol and prior to dosing with GSK256066. Participants were resting in the body box for at least 1 minute prior to any assessments. Smoking and short acting bronchodilators should be avoided 6 hour prior to administration of the salbutamol. It was assessed on Baseline (Day 0) and 27. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): plethysmography measures: specific airway conductance (sGaw)
Plethysmography procedures was performed 30 minutes after dosing with salbutamol and prior to dosing with GSK256066. Participants were resting in the body box for at least 1 minute prior to any assessments. Smoking and short acting bronchodilators should be avoided 6 hour prior to administration of the salbutamol. It was assessed on Baseline (Day 0) and 27. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): impulse oscillometry (IOS): total resistance (R5) and large airway resistance (R25); low frequence reactance (X5)
IOS tests were performed prior to other measurements of pulmonary function to avoid any influence of forced expiratory manoeuvres on airway function during resting breathing. IOS test was performed before and 30 minutes after dosing with salbutamol and before dosing with GSK256066. Smoking and short acting bronchodilators should be avoided 6 hour prior to administration of the salbutamol. It was assessed on Baseline (Day 0) and 27. Observations with BTR grading of 'not acceptable' were excluded. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): IOS-resonant frequency (RF)
IOS tests were performed prior to other measurements of pulmonary function to avoid any influence of forced expiratory manoeuvres on airway function during resting breathing. IOS test was performed before and 30 minutes after dosing with salbutamol and before dosing with GSK256066. Smoking and short acting bronchodilators should be avoided 6 hour prior to administration of the salbutamol. It was assessed on Baseline (Day 0) and 27. Observations with BTR grading of 'not acceptable' were excluded. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): impulse oscillometry (IOS): peripheral resistance (R5-R15) and R15
IOS tests were performed prior to other measurements of pulmonary function to avoid any influence of forced expiratory manoeuvres on airway function during resting breathing. IOS test was performed before and 30 minutes after dosing with salbutamol and before dosing with GSK256066. Smoking and short acting bronchodilators should be avoided 6 hour prior to administration of the salbutamol. It was assessed on Baseline (Day 0) and 27. Observations with BTR grading of 'not acceptable' were excluded. The parameter 'R5-R15' was derived by subtracting R15 from R5 for each subject at each time point.
Measured: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): IOS-low frequence reactance area (AX)
IOS tests were performed prior to other measurements of pulmonary function to avoid any influence of forced expiratory manoeuvres on airway function during resting breathing. IOS test was performed before and 30 minutes after dosing with salbutamol and before dosing with GSK256066. Smoking and short acting bronchodilators should be avoided 6 hour prior to administration of the salbutamol. It was assessed on Baseline (Day 0) and 27. Observations with BTR grading of 'not acceptable' were excluded.
Measured: Up to Day 27 (Visit 6a)
The concentration of serum inflammatory biomarkers: fibrinogen
Blood samples were collected to determine serum concentrations of inflammation biomarkers such as fibrinogen, tumour necrosis factor (TNF)-alpha, soluble TNF receptors (sTNF-Rs), IL-8, IL-6, IL-1-beta using an appropriately validated assay including ELISA and multiplex analysis. TNFα, sTNF-Rs, IL-8, IL-6 and IL-1-beta data were not collected. Values below LLQ or above ULQ have been imputed to half the LLQ or ULQ. LLQ for fibrinogen-0.4 grams per liter and ULQs for fibrinogen-14 grams per liter. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 28 (Visit 6b)
The concentration of serum inflammatory biomarkers: surfactant protein-D (SP-D)
Blood samples were collected to determine serum concentrations of inflammation biomarkers such as fibrinogen, tumour necrosis factor-alpha (TNF-alpha), sTNF-Rs, IL-8, IL-6, IL-1-beta using an appropriately validated assay including ELISA and multiplex analysis. TNFα, sTNF-Rs, IL-8, IL-6 and IL-1-beta data were not collected. Surfactant protein D (SP-D) was collected. Values below LLQ or above ULQ have been imputed to half the LLQ or ULQ. LLQ for SP-D-7.8 nanograms per mL and ULQs for SP-D-2000 nanograms per mL. Data for adjusted mean is presented as least square mean.
Measured: Up to Day 28 (Visit 6b)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2007 (estimated)
- Study start4 Oct 2007
- Primary completion15 Dec 2008
- Study completion15 Dec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00549679
- Sponsor's protocol ID
- IPC101939
- Status last verified
- Jul 2017
- First submitted
- 24 Oct 2007
- Last updated
- 28 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23701917
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety and Tolerability of Inhaled GSK256066 in Mild to Moderate COPD Patients
- ClinicalTrials.gov ID
- NCT00549679
- Acronym / sponsor ID
- IPC101939
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- Chronic Obstructive Pulmonary Disease (COPD), COPD, Repeat Dose, GSK256066
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 4 Oct 2007
- Primary completion
- 15 Dec 2008 (actual)
- Study completion
- 15 Dec 2008 (actual)
- First posted
- 26 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and tolerability of the cfor the first time in mild to moderate COPD patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 25 mcg | Experimental | Drug: GSK25606625 microgram inhaled once daily |
| 87.5 mcg | Experimental | Drug: GSK25606687.5 microgram inhaled once daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo inhaled once daily |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (32 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK256066PDE4 inhibitor | Drug | 25 mcg, 87.5 mcg |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time frame: Up to follow up (approximately 56 days)
An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention.
Change from Baseline (Day 0 [pre-bronchodilator]) in 12-lead electrocardiogram (ECG) findings
Time frame: Baseline (Day 0 [pre-bronchodilator]) and up to Day 28 (Visit 6b)
ECG parameters consist of QT interval corrected by Bazett's (QTcB) and Fridericia's (QTcF) formulas, QT interval, QRS duration and PR interval. Baseline was defined as value at Day 0 (pre-bronchodilator). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was the mean of the 3 pre-salbutamol measurements at Day 0. It was assessed on Baseline, Day 1, 7, 14, 15, 21, 27 and 28. Post Baseline, ECG was performed 1-2 hours post dose.
Change from Baseline (Day 0 [pre-bronchodilator]) in 12-lead electrocardiogram (ECG) findings-ventricular rate
Time frame: Baseline (Day 0 [pre-bronchodilator]) and up to Day 28 (Visit 6b)
ECG parameters consist of ventricular rate. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was the mean of the 3 pre-salbutamol measurements at Day 0. It was as/sessed on Baseline, Day 1, 7, 14, 15, 21, 27 and 28. Post Baseline, ECG was performed 1-2 hours post dose.
Number of participants with abnormal (potential clinical importance [PCI]) systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR)
Time frame: Up to Day 27 (Visit 6a)
The PCI range for SBP was < 85 and > 160 millimeters of mercury (mmHg), DBP was < 45 and > 100 mmHg and for HR < 40 and > 110 beats per minute. It was assessed on Baseline (pre-bronchodilator), Day 14 and 27. Data for SBP high, SBP low, DBP high, DBP low, HR high and HR low is presented.
Number of participants with abnormal (PCI) clinical chemistry
Time frame: Up to Day 42 (follow up visit)
Clinical chemistry included: albumin, bicarbonate, alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), blood urea, creatinine, magnesium, sodium, potassium, chloride, glucose, total bilirubin, direct bilirubin, indirect bilirubin, total protein, gamma glutamyltransferase (GGT), calcium, creatinine kinase, creatine kinase-MB, creatinine clearance (estimated; male and female), lactate dehydragenase, and troponin, triglycerides. Data for abnormal parameters (above and below range) is provided. It was assessed on Baseline (Day -3), Day 14, 28 and on follow up visit (Day 42). Data for only abnormal observations is presented.
Number of participants with abnormal (PCI) hematology
Time frame: Up to Day 42 (follow up visit)
Hematology included: haemoglobin, haematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell (RBC) indices, white blood cell (WBC), basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. Data for abnormal parameters (above and below range) is provided. It was assessed on Baseline (Day -3), Day 14, 28 and on follow up visit (Day 42). Data for only abnormal observations is presented.
Number of participants with abnormal urinalysis
Time frame: Up to Day 56 (Visit follow up)
Abnormal urinalysis data for RBC in urine and haematuria presented. Data for abnormal parameters (above and below range) is provided. It was assessed on Baseline (Day -3), Day 7, 14, 21, 28 and on follow up visit (Day 42). Data for only abnormal observations is presented.
Change from Baseline (Day 0) in lung function parameters: forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)
Time frame: Baseline (Day 0) and up to Day 27 (Visit 6a)
The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline value defined as the value on Day 0. It was assessed on Baseline (Day 0), Day 14 and 27. Spirometry tests was performed before and 30 minutes after dosing with salbutamol (bronchodilator) on Day 0 and before dosing with GSK256066. As they were analyzed separately, there were two Baselines for these tests, 'pre bronchodilator Baseline' and 'post bronchodilator Baseline'. Smoking and short acting bronchodilators were avoided 6 hour prior to administration of the salbutamol. Observations with best test review (BTR) grading of 'not acceptable' were excluded.
Number of participants with abnormal Holter interpretations
Time frame: Up to Day 27 (Visit 6a)
Holter parameters were derived by visit over the 24 hour period as: maximum HR over 24 hours was the maximum HR of all time slices and mean HR over 24 hours was the mean HR of all time slices, weighted by the time length of each slice. The total number of ventricular runs and the number of supraventricular runs over 24 hours were derived by summing each count across all time slices. Data for normal, abnormal: not clinically significant and abnormal: clinically significant is presented. It was assessed on Baseline (Day 0), Day 14and 27. Data for normal, abnormal: clinically significant and abnormal: clinically not significant presented.
Number of participants who withdrawn for exacerbations of chronic obstructive pulmonary disease (COPD)
Time frame: Up to Day 27 (Visit 6a)
An exacerbation of COPD was defined as worsening of COPD symptoms requiring changes to normal treatment including antimicrobial therapy, short courses of oral steroids and other bronchodilator therapy. If clinically indicated, short-term treatment with antibiotics could be prescribed for the exacerbation. Any participants requiring treatment with inhaled or oral corticosteroids or admission to hospital were withdrawn from the study.
23 secondary outcomes
Plasma concentrations of GSK256066 and active metabolite GSK614917 and derived pharmacokinetic parameters: area under the plasma drug concentration versus time curve (AUC0-last)
Time frame: Pre-dose and at 15, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hour post dosing at Baseline (Visit 2a) and Days 14 and 27 (Visits 4a and 6a)
Plasma concentrations of GSK256066 and active metabolite GSK614917 and derived pharmacokinetic parameters: maximum observed plasma drug concentration (Cmax)
Time frame: Pre-dose and at 15, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hour post dosing at Baseline (Visit 2a) and Days 14 and 27 (Visits 4a and 6a)
Plasma concentrations of GSK256066 and GSK614917 and derived pharmacokinetic parameters: time to maximum observed plasma drug concentration (tmax)
Time frame: Pre-dose and at 15, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hour post dosing at Baseline (Visit 2a) and Days 14 and 27 (Visits 4a and 6a)
Change from Baseline (Day -3) total cell number (cells/mL) in induced sputum
Time frame: Baseline (Day -3) and Day 28 (Visit 6b)
Change from Baseline (Day -3) in neutrophils and macrophages as a percentage of total cells in induced sputum
Time frame: Baseline (Day -3) and Day 28 (Visit 6b)
Summary of mean lymphocytes, bronchial epithelial cells and eosinophils as a percentage of total cells in induced sputum
Time frame: Up to Day 28 (Visit 6b)
Absolute numbers of leukocytes, neutrophils and macrophages in induced sputum
Time frame: Up to Day 28 (Visit 6b)
Absolute numbers of bronchial epithelial cells, lymphocytes and eosinophils in induced sputum
Time frame: Up to Day 28 (Visit 6b)
Summary of concentration of total protein in induced sputum supernatant
Time frame: Up to Day 28 (Visit 6b)
The concentration of inflammatory biomarkers in induced sputum supernatant: interleukin (IL) 8
Time frame: Up to Day 28 (Visit 6b)
The concentration of inflammatory biomarkers in induced sputum supernatant: myeloperoxidase (MPO)
Time frame: Up to Day 28 (Visit 6b)
Summary of messenger ribonucleic acid (mRNA) and/or protein in induced sputum of established and exploratory markers of inflammation: IL-6, IL-1 beta and IL-8
Time frame: Day 28 (Visit 6b)
Summary of mRNA and/or protein in induced sputum of established and exploratory pharmacodynamic markers: Phosphodiesterase-4 B (PDE4B), SNF1 like kinase (SNF1LK)
Time frame: Up to Day 28 (Visit 6b)
Summary of lung function parameters (pre and post-bronchodilator): mean spirometry measures FEV1 and FVC
Time frame: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): plethysmography measures: inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), slow vital capacity (SVC) and thoracic gas volume (TGV)
Time frame: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): plethysmography measures: plus airway resistance (Raw)
Time frame: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): plethysmography measures: specific airway conductance (sGaw)
Time frame: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): impulse oscillometry (IOS): total resistance (R5) and large airway resistance (R25); low frequence reactance (X5)
Time frame: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): IOS-resonant frequency (RF)
Time frame: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): impulse oscillometry (IOS): peripheral resistance (R5-R15) and R15
Time frame: Up to Day 27 (Visit 6a)
Summary of lung function parameters (pre and post-bronchodilator): IOS-low frequence reactance area (AX)
Time frame: Up to Day 27 (Visit 6a)
The concentration of serum inflammatory biomarkers: fibrinogen
Time frame: Up to Day 28 (Visit 6b)
The concentration of serum inflammatory biomarkers: surfactant protein-D (SP-D)
Time frame: Up to Day 28 (Visit 6b)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2017.
- Derived from this study: PubMed 23701917Watz 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
15 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK256066 in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 15 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Russia, Germany, Netherlands, Slovakia, Estonia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (AEs) and serious adverse events (SAEs) (time frame: Up to follow up (approximately 56 days)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00549679, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2017.