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A 12 Week Study To Assess Efficacy And Safety Of GW856553 In Subjects With Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00642148
First received: March 17, 2008
Last updated: March 10, 2011
Last verified: March 2011
  Purpose

Phase IIa, randomised, double-blind, double-dummy, parallel group, multi-centre study in subjects diagnosed with moderate chronic obstructive pulmonary disease (COPD). The primary objective is to evaluate the effects of 12-weeks of treatment with GW856553 7.5 mg twice daily (BID) compared with placebo on the percentage of sputum neutrophils at 12 weeks. Twelve weeks of treatment with SERETIDE 50/500 BID will be compared with placebo for effect on sputum neutrophils as a positive control arm in the study


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Chronic Obstructive Airway Disease
Drug: GW856553
Drug: Placebo
Drug: Seretide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12-week, Randomised, Double-blind, Placebo-controlled Study to Assess the Anti-inflammatory Activity, Efficacy and Safety of GW856553 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To evaluate the effects if 12 wks of treatment with GW856553 7.5 mg BID compared with placebo on the percentage of sputum neutrophils at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the effects if 12 wks of treatment with GW856553 7.5 mg BID compared with placebo on pulmonary function assesses by body plethysmography, by spirometry and by impulse oscillometry [ Designated as safety issue: No ]
  • Plethysmography measures: IC, RV, TGV at FRC, TLC, SVC. [ Designated as safety issue: No ]
  • Spirometry measures: FVC, FEV1, FEV1/FVC. [ Designated as safety issue: No ]
  • Impulse oscillometry (Jaeger IOS).Peripheral airway resistance (R5 - R15).Total resistance (R5) and large airway resistance (R25). [ Designated as safety issue: No ]
  • Resonant frequency, X5 and low-frequency reactance area (AX) as indicators of the reactive capacitance properties of the lung. [ Designated as safety issue: No ]
  • Serum fibrinogen and additional systemic inflammation biomarkers (e.g. serum IL1β, clara cell protein 16, SP-D, MMP9, CXCL5, and CXCL8). [ Designated as safety issue: No ]
  • Levels of ex vivo lipopolysaccharide (LPS) induced tumour necrosis factor (TNF-alpha) in whole blood pre-dose and 2 h post-dose at selected centres. [ Designated as safety issue: No ]
  • Levels of ex vivo sorbitol induced phosphorylation of heat shock protein 27 (pHSP27) in whole blood pre-dose and 2 h post-dose at selected centres. [ Designated as safety issue: No ]
  • Parameters measured in induced sputum:─Total cell count (cells/mL) ─ Macrophages, lymphocytes and eosinophils as a percentage of total cells. ─ Neutrophils, macrophages, lymphocytes and eosinophils as absolute inflammatory cell numbers. [ Designated as safety issue: No ]
  • ─ Sputum weight and volume (Exploratory) ─ The concentration of inflammatory biomarkers (including but not limited to myeloperoxidase and total protein) [ Designated as safety issue: No ]

Enrollment: 306
Study Start Date: February 2008
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Seretide Drug: Placebo
Placebo tablet and inhaler
Drug: Seretide
Active comparator inhaler
Placebo Comparator: Placebo
Placebo tablet
Drug: Placebo
Placebo tablet and inhaler
Experimental: GW856553 Drug: GW856553
Active tablet
Other Name: GW856553
Drug: Placebo
Placebo tablet and inhaler

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects eligible for enrolment in the study must meet all of the following criteria:

  • Male adults or female adults of non-childbearing potential who are between 40 and 75 years of age (inclusive). Note: a female is eligible to enter and participate in the study if she is of non-childbearing potential (i.e. physiologically incapable of becoming pregnant). This includes any female who is post-menopausal. For the purposes of this study, post menopausal is defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. Postmenopausal status may be confirmed by serum FSH and oestradiol concentrations at screening if deemed necessary by the PI. Surgical sterility will be defined as females who have had a hysterectomy and/or bilateral oophorectomy or tubal ligation.
  • Chronic obstructive pulmonary disease diagnosis: an established clinical history of COPD in accordance with the following description by the American Thoracic Society/European Respiratory Society [American Thoracic Society / European Respiratory Society, 2004] Chronic obstructive pulmonary disease is a preventable and treatable disease characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.
  • 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 capable of providing signed written informed consent to participate.
  • Subjects must have a QTc <450 msec on baseline ECG or triplicate ECG averaged over a brief recording interval. For subjects with baseline bundle branch block the QTc will be <480msec on baseline ECG or triplicate ECG averaged over a brief recording interval.
  • A subject will be eligible for randomisation at the end of the run-in period only if the following additional criterion applies: Subjects with no evidence of an ongoing acute infection or sinus symptoms Specific information regarding warnings, precautions, contraindications, AEs, and other pertinent information on the investigational product that may impact subject eligibility is provided in the Investigator Brochure/Investigator Brochure supplement(s), product label, and other pertinent documents.

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

  • Women who are pre-menopausal and of child-bearing potential, or pregnant.
  • Subjects with a primary diagnosis of asthma or α-1 antitrypsin deficiency.
  • 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 Visit 1
  • Subjects with active tuberculosis or being treated for 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 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 (see Section 6.6.1).
  • Subjects with clinically significant gastrointestinal or hepatic abnormalities.
  • Subjects with hypoxaemia. (All subjects must have an O2 saturation of ≥ 88% on room air).
  • History of Gilbert's syndrome. Subjects with a total bilirubin concentration above the upper limit of normal at Visit 1 will be excluded.
  • Liver function tests (bilirubin, ALT, or AST) above upper limit of normal at Visit 1. The subject has a positive Hepatitis B surface antigen or Hepatitis C antibody result within 3 months of the start of the study.The subject has a history of HIV or other immunosuppressive disease.
  • Subjects who have undergone recent surgery including lung volume reduction surgery or have conditions that prevent them from performing spirometry.
  • Subjects with a history (or suspected history) of alcohol misuse or any other substance abuse.
  • The subject has a three month prior history of regular alcohol consumption exceeding an average weekly intake of > 21 units (or an average daily intake of greater than 3 units) for males, or an average weekly intake of > 14 units (or an average daily intake of greater than 2 units) for females. 1 unit is equivalent to a half-pint (284mL) of beer/lager; 25mL measure of spirits or 125mL of wine; or a positive alcohol breath test at the screening visit
  • Subjects who will commence or who are likely to commence statin therapy (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) or treatment with intranasal or topical corticosteroids, acetylsalicyclic acid, non-steroidal anti-inflammatory drugs, gemfibrozil, clopidogrel, abciximab, peroxidase proliferator-activated receptor γ agonists (e.g, rosiglitazone), fibrates, or niacin from Visit 1 until study completion. (Subjects who are receiving these medications at a stable dose at Visit 1 may be entered in the study.)
  • Subjects who require treatment with any of the following from the Visit 1 until study completion:

    • Inhaled corticosteroids
    • Inhaled cromolyn sodium or nedocromil
    • Xanthines (theophylline preparations)
    • Leukotriene modifiers
    • Tiotropium
    • Long-acting inhaled β2-agonists (salmeterol, formoterol)
    • Oral β2-agonists
    • Macrolide antibiotics for more than five days
  • Subjects who have received treatment with oral, intravenous or intra-articular corticosteroids within 6 weeks of Visit 1 or thereafter.
  • 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. Maintenance rehabilitation is permitted.
  • 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 Visit 1
  • An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women; or unwillingness of the male subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as an intra-uterine devices, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation if the woman could become pregnant from the time of the first dose of investigational product for the duration of the study (i.e., through the follow-up phase).
  • Subjects who have had a close household contact treated for active tuberculosis within the past 12 months, or who in the judgement of the investigator are at high risk for developing active tuberculosis, shall be excluded from the study.
  • A subject will not be eligible for randomisation at the end of the run-in period if either of the following criteria applies:

    • Subjects who have experienced an exacerbation during the run-in period requiring treatment with oral corticosteroids and/or antibiotics and/or hospitalisation.
    • Subjects who are unable to produce an induced sputum sample.
  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: NCT00642148

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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: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00642148     History of Changes
Other Study ID Numbers: MKI102428
Study First Received: March 17, 2008
Last Updated: March 10, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by GlaxoSmithKline:
GW856553
p38 MAPK
Chronic Obstructive Pulmonary Disease

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

ClinicalTrials.gov processed this record on November 20, 2014