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

NCT00549679 | Completed Phase 2

• 1 other identifier: IPC101939
• Study Type: interventional
• Target: 104
• Locations: 6 countries
• Sites: 15

Brief Summary

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

Keywords

Chronic Obstructive Pulmonary Disease (COPD); COPD; Repeat Dose; GSK256066

Outcome Measures

Primary Outcomes (10)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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)

  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)

  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)

  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

  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

  Baseline (Day -3) and Day 28 (Visit 6b)

Study Arms (3)

25 mcg

EXPERIMENTAL

25 microgram inhaled once daily

Drug: GSK256066

87.5 mcg

EXPERIMENTAL

87.5 microgram inhaled once daily

Drug: GSK256066

Placebo

PLACEBO COMPARATOR

Placebo inhaled once daily

Drug: Placebo

Interventions

GSK256066 DRUG

PDE4 inhibitor

25 mcg; 87.5 mcg

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Tallinn, 13419, Estonia

Location

GSK Investigational Site

Tampere, 33520, Finland

Location

GSK Investigational Site

Gauting, Bavaria, 82131, Germany

Location

GSK Investigational Site

Berlin, 10717, Germany

Location

GSK Investigational Site

Hamburg, 22291, Germany

Location

GSK Investigational Site

Hoorn, 1624 NP, Netherlands

Location

GSK Investigational Site

Horn, 6085 NM, Netherlands

Location

GSK Investigational Site

Veldhoven, 5504 DB, Netherlands

Location

GSK Investigational Site

Barnaul, 656 045, Russia

Location

GSK Investigational Site

Moscow, 105 077, Russia

Location

GSK Investigational Site

Saint Petersburg, 197022, Russia

Location

GSK Investigational Site

Yaroslavl, 150003, Russia

Location

GSK Investigational Site

Bratislava, 826 06, Slovakia

Location

GSK Investigational Site

Košice, 041 90, Slovakia

Location

GSK Investigational Site

Martin, 036 59, Slovakia

Location

Related Publications (1)

• 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.

  PMID: 23701917 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

6-((3-((dimethylamino)carbonyl)phenyl)sulfonyl)-8-methyl-4-((3-methyloxyphenyl)amino)-3-quinolinecarboxamide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2007
• First Posted: October 26, 2007
• Study Start: October 4, 2007
• Primary Completion: December 15, 2008
• Study Completion: December 15, 2008
• Last Updated: July 28, 2017

Record last verified: 2017-07

Locations

SL (3); DE (3); FI (1); NL (3); ES (1); RU (4)