Chronic Obstructive Pulmonary Disease MedDRA version: 18.0 Level: LLT Classification code 10010953 Term: COPD exacerbation System Organ Class: 100000004855
Conditions
Interventions
Product Name: GSK2269557
Product Code: GSK2269557
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Not available yet
CAS Number: 1364799-98-3
Other descriptive name: GSK2269557
Concentratio
Sponsors
GlaxoSmithKline Reasearch & Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) AGE -Between 40 and 80 years of age inclusive, at the time of signing the informed consent. 2) TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY -The subject has a confirmed and established diagnosis of COPD, as defined by the GOLD guidelines for at least 6 months prior to entry. -The subject has a post-bronchodilator FEV1/FVC or= 45 kg and body mass index (BMI) within the range 18 – 32 kg/m2 4) SEX -Male -Female subject: is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: 1. Non-reproductive potential defined as: -Pre-menopausal females with one of the following: -Documented tubal ligation -Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion -Hysterectomy -Documented Bilateral Oophorectomy -Postmenopausal defined as 12 months of spontaneous amenorrhea. Females whose menopausal status is in doubt will be required to use, or have been using, one of the highly effective contraception methods as specified below from 30 days prior to the first dose of study medication and until completion of the follow-up visit. 2. Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until completion of the follow-up visit. GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penilevaginal intercourse on a long term and persistent basis. 1. Contraceptive subdermal implant that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label 2. Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label 3. Oral Contraceptive, either combined or progestogen alone 4. Injectable progestogen 5. Contraceptive vaginal ring 6. Percutaneous contraceptive patches 7. Male partner sterilization with documentation of azoospermia prior to the female subject’s entry into the study, and this male is the sole partner for that subject. 8. Male condom combined with a vaginal spermicide. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how t
Exclusion criteria
Exclusion criteria: 1) CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER FUNCTION AND QTC INTERVAL) To avoid recruitment of subjects with a severe COPD exacerbation, the presence of any one of the following severity criteria will render the subject ineligible for inclusion in the study: -Need for invasive mechanical ventilation (short term (2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 450 msec or QTcF > 480 msec in subjects with Bundle Branch Block, based on single QTcF value. -Subjects who have undergone lung volume reduction surgery. 20 CONCOMITANT MEDICATIONS -Subject is currently on chronic treatment with macrolides; long term oxygen therapy (> 15 hours/day). -The subject has been on chronic treatment with anti-Tumour Necrosis Factor (anti- TNF), anti-Interleukin-1 (anti-IL1), or any other immunosuppressive therapy within 60 days prior to dosing. 3) RELEVANT HABITS -History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >28 units for males or >21 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. 4) CONTRAINDICATIONS -History of sensitivity to any of the study medications, or components thereof (such as lactose) or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. 5) DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA -A known (historical) positive t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Screening, Day 12 and Day 28;Secondary Objective: -To evaluate the effect of once daily repeat inhaled doses of GSK2269557 on lung parameters derived from HRCT scans in subjects with acute exacerbation of COPD, compared to placebo -To assess the safety and tolerability of once daily repeat inhaled doses of GSK2269557 administered to subjects with acute exacerbation of COPD, compared to placebo -To evaluate the plasma PK of once daily repeat inhaled doses of GSK2269557 administered to subjects with acute exacerbation of COPD. -To evaluate the effect of once daily repeat inhaled doses of GSK2269557 on lung function parameters in subjects with acute exacerbation of COPD, compared to placebo -To evaluate the number of treatment failures of once daily repeat inhaled doses of GSK2269557 administered to subjects with acute exacerbation of COPD, compared to placebo -To evaluate the time to next exacerbation after once daily repeat inhaled doses of GSK2269557 administered to subjects with acute exacerbation of COPD, compared to placebo;Main Objective: To evaluate the effect of once daily repeat inhaled doses of GSK2269557 on lung parameters derived from HRCT scans in subjects with acute exacerbation of COPD, compared to placebo;Primary end point(s): Change from baseline in specific imaging Airways Volume: siVaw at FRC and TLC | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Change from baseline in imaging Airways Volume: iVaw at FRC and TLC •Change from baseline in imaging Airways resistance and specific airways resistance: iRaw, siRaw at FRC and TLC •Change from baseline in imaging Total lung capacity and Lung lobar volumes at FRC and TLC after •Change from baseline in imaging trachea length/diameter •Adverse events (AEs) •Hematology, clinical chemistry •Vital signs •12-lead ECG •Day 1 plasma exposure up to 24 hours post dose for inpatients •PK Trough concentration after 12 days, 28 days, 56 days and 84 days of treatment. •Changes from baseline in FEV1 measured daily •Changes from baseline in PEF measured daily •Changes from baseline in Diffusion capacity (DLco, Kco) after 28 days and after 84 days of treatment •Changes from baseline in Whole body plethysmography after 28 days and after 84 days of treatment, to include: •Reliever use post-discharge (beta2-agonist and / or anticholinergic) in addition to regular therapy. •Questionnaires CAT and MMRC scale at baseline, 28 days and 84 days •Number of treatment failures as defined by at least one of: 1.Recurrent exacerbations 2.Prolonged treatment of current exacerbation (beyond 14 days) 3.Requirement for invasive mechanical ventilation •Time to next exacerbation;Timepoint(s) of evaluation of this end point: •Change from baseline in imaging Screening, Day 12 and Day 28 •Adverse events (AEs) •Number of treatment failures •Time to next exacerbation From start of study treatment until follow-up contact •Hematology, clinical chemistry, Vital signs, 12-lead ECG Screening, Day 1, Day 12, Day 28, Day 56, Day 84 •Day 1 plasma exposure up to 24 hours post dose predose, 5 min, 3 and 24h postdose •PK Trough concentration Day 12, Day 28, Day 56 and Day 84 •Changes from baseline in FEV1 and PEF measured daily •Reliever use post-discharge in addition to regular therapy. From Day 1 to Day 84 •Changes from baseline in Diffusion | — |
Countries
Belgium, Denmark, Netherlands, Romania
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed