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

NCT00642148 | Completed Phase 2

• 1 other identifier: MKI102428
• Study Type: interventional
• Target: 306
• Locations: 12 countries
• Sites: 31

Brief Summary

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

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

GW856553; p38 MAPK; Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in percentage of neutrophils in induced sputum at Week 12

  Induced sputum samples were collected at Baseline (Week 0), Week 4 and at Week 12 to evaluate the effects of 12 weeks of treatment with GW856553 7.5 mg twice daily. Baseline was defined at Week 0. Change from Baseline in neutrophil count was calculated as the Week 12 value minus the Baseline value (percentage of neutrophil of total cells in induced sputum at Week 12 minus the Baseline value). Data for adjusted mean was presented for least square mean.

  Baseline (Week 0) and Week 12

Secondary Outcomes (21)

• Change from Baseline in Plethysmography measures at Week 12

  Baseline (Week 0) and Week 12

• Change from Baseline in pulmonary function assessed by forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) at Week 12

  Baseline (Week 0) and Week 12

• Change from Baseline in pulmonary function assessed by FEV1/FVC at Week 12

  Baseline (Week 0) and Week 12

• Change from Baseline in pulmonary function assessed by impulse oscillometry [Peripheral airway resistance (R5 - R15)] at Week 12

  Baseline (Week 0) and Week 12

• Change from Baseline in pulmonary function assessed by impulse oscillometry: Total resistance (R5) and large airway resistance (R25) of the lung at Week 12

  Baseline (Week 0) and Week 12

Study Arms (3)

Seretide

ACTIVE COMPARATOR

Drug: Placebo; Drug: Seretide

Placebo

PLACEBO COMPARATOR

Placebo tablet

Drug: Placebo

GW856553

EXPERIMENTAL

Drug: GW856553; Drug: Placebo

Interventions

GW856553 DRUG

Active tablet

GW856553

Placebo DRUG

Placebo tablet and inhaler

GW856553; Placebo; Seretide

Seretide DRUG

Active comparator inhaler

Seretide

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (31)

GSK Investigational Site

Tallinn, 13419, Estonia

Location

GSK Investigational Site

Tartu, 51014, Estonia

Location

GSK Investigational Site

Helsinki, 00290, Finland

Location

GSK Investigational Site

Gauting, Bavaria, 82131, Germany

Location

GSK Investigational Site

Mainz, Rhineland-Palatinate, 55131, Germany

Location

GSK Investigational Site

Magdeburg, Saxony-Anhalt, 39112, Germany

Location

GSK Investigational Site

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

GSK Investigational Site

Lübeck, Schleswig-Holstein, 23552, Germany

Location

GSK Investigational Site

Berlin, 10717, Germany

Location

GSK Investigational Site

Riga, LV1002, Latvia

Location

GSK Investigational Site

Klaipėda, LT-92231, Lithuania

Location

GSK Investigational Site

Breda, 4819 EV, Netherlands

Location

GSK Investigational Site

Heerlen, 6419 PC, Netherlands

Location

GSK Investigational Site

Veldhoven, 5504 DB, Netherlands

Location

GSK Investigational Site

Auckland, 1005, New Zealand

Location

GSK Investigational Site

Wellington, 6035, New Zealand

Location

GSK Investigational Site

Barnaul, 656 045, Russia

Location

GSK Investigational Site

Moscow, 105 229, Russia

Location

GSK Investigational Site

Saint Petersburg, 194044, Russia

Location

GSK Investigational Site

Saint Petersburg, 197 089, Russia

Location

GSK Investigational Site

Kamnik, 1241, Slovenia

Location

GSK Investigational Site

Ljubljana, 1000, Slovenia

Location

GSK Investigational Site

Cape Town, Gauteng, 7505, South Africa

Location

GSK Investigational Site

eManzimtoti, 4126, South Africa

Location

GSK Investigational Site

Mowbray, 7700, South Africa

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Seoul, 136-705, South Korea

Location

GSK Investigational Site

Seoul, 137-701, South Korea

Location

GSK Investigational Site

Headington, Oxfordshire, OX3 7LJ, United Kingdom

Location

GSK Investigational Site

Cottingham, East Yorkshire, HU16 5JQ, United Kingdom

Location

GSK Investigational Site

London, E2 9JX, United Kingdom

Location

Related Publications (1)

• Lomas DA, Lipson DA, Miller BE, Willits L, Keene O, Barnacle H, Barnes NC, Tal-Singer R; Losmapimod Study Investigators. An oral inhibitor of p38 MAP kinase reduces plasma fibrinogen in patients with chronic obstructive pulmonary disease. J Clin Pharmacol. 2012 Mar;52(3):416-24. doi: 10.1177/0091270010397050. Epub 2011 Nov 16.

  PMID: 22090363 BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide; Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fluticasone; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 17, 2008
• First Posted: March 24, 2008
• Study Start: February 14, 2008
• Primary Completion: July 27, 2009
• Study Completion: July 27, 2009
• Last Updated: August 18, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

ES (2); LA (1); KR (3); FI (1); SL (2); DE (6); GB (3); RU (4); LI (1); NL (3); ZA (3); NZ (2)