Chronic Obstructive Pulmonary Disease MedDRA version: 17.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Conditions
Interventions
Product Name: GSK2269557 DISKUS™ Inhalation Powder
Product Code: GSK2269557
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: GSK2269
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject has a confirmed and established diagnosis of COPD, as defined by the GOLD guidelines (see Appendix 4). 2. Male or female of non-child bearing potential between 40 and 75 years of age inclusive, at the time of signing the informed consent. 3.The subject has a post-bronchodilator (400 µg salbutamol) FEV1/FVC 100 mg of sputum at screening. 6.Body weight = 45 kg and BMI within the range 17 – 32 kg/m2 (inclusive). 7.A female subject is eligible to participate if she is of: - Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy, salpingo-oophrectomy or oophrectomy [for this definition, “documented” refers to the outcome of the investigator's/designee’s review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones and cholecystectomy). 2. Subjects who have a past or current medical conditions or diseases that are not well controlled and, which as judged by the Investigator, may affect subject safety or influence the outcome of the study. (Note: Patients with adequately treated and well controlled concurrent medical conditions (e.g. hypertension) ARE permitted to be entered into the study). 3. Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the Investigator, compromise the safety of the subject or affect the interpretation of the results. 4. 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. 5. History of sensitivity to any of the study medications, or components (such as lactose) thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. 6. A positive test for HIV antibody - tested according to local policies. 7. The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include cannabinoids, amphetamines, barbiturates, cocaine and opiates. The detection of drugs (e.g. benzodiazepines, opiates) taken for a legitimate medical purpose would not necessarily be an exclusion to study participation. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study. 8. A positive pre-study Hepatitis B surface antigen (HBs-Ag) or positive total hepatitis B core antibody (anti-HBc) or positive Hepatitis C antibody result within 3 months. 9. Pregnant females as determined by positive urine hCG test at screening or prior to dosing. 10. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. 11. Lactating females. 12. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 13. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 14. Subject has poorly controlled or unstable COPD, defined as the occurrence of any of the following: - Either: acute worsening of COPD (an exacerbation) that is managed by the subject at home requiring treatment with corticosteroids and/or antibiotics in the 4 weeks prior to the screening visit. - Or: more than two exacerbations in the previous 2 months prior to the screening visit that required a course of oral corticosteroids and/or antibiotics, or for which the subject was hospitalised. 15. Subject has had a respiratory tract infection treated with antibiotics in the 4 weeks prior to first dose. 16. Subject requires regular treatment with oral corticosteroids or has received oral or parenteral corticosteroids within 4 weeks of screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A To assess the safety and tolerability of repeat doses of GSK2269557 administered as a dry powder to COPD patients. Part B To characterise the dose-response relationship of repeat doses of GSK2269557 administered as a dry powder to COPD patients using inflammatory cytokine biomarker.;Secondary Objective: To determine the pharmacokinetic profile of repeat doses of GSK2269557 administered as a dry powder to COPD patients. To determine the effect on recue medication usage of repeat doses of GSK2269557 administered as a dry powder to COPD patients. Part B only: To assess the safety and tolerability of repeat doses of GSK2269557 administered as a dry powder to COPD patients;Primary end point(s): Part A • Adverse events (AEs) • Hematology and Clinical Chemistry • Vital signs • 12-lead ECG • Pulmonary Function Tests (FEV1) Part B •Induced Sputum cytokine concentrations on Day 7 and Day 15;Timepoint(s) of evaluation of this end point: Part A: Adverse events (AEs): from start of study treatment until follow-up contact; Hematology and Clinical Chemistry: screening, Day 1 predose, Day 7 predose, Day 15 and follow-up visit; Vital signs: Screening, Day 1 (predose, 30 min postdose, 6h postdose), Day 7 predose, Day 15 and follow-up visit; 12-lead ECG: Screening, Day 1 (predose, 30 min postdose, 6h postdose), Day 7 predose, Day 15 and follow-up visit; Pulmonary Function Tests (FEV1): Screening, Day 1 (predose, 1h postdose), Day 7 (predose, 1h postdose), Day 15 and follow-up visit Part B: Cytokine concentration: Day -7, Day 1, Day 7 and Day 15 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A • Day 1 plasma exposure up to 6 hours post dose • Maximum observed plasma drug concentration: Cmax on Day 7. • Trough concentration (Ct) on Day 6/7 and on Day 15 • Rescue medication usage Part B only •Adverse events (AEs) •Hematology and Clinical Chemistry •Vital signs •12-lead ECG •Pulmonary Function Tests (FEV1) ;Timepoint(s) of evaluation of this end point: Part A&B: PK samples collected at Day 1 (predose, 5m, 30m, 1h, 2h, 4h, 6h), Day 7 (predose, 5m postdose), Day 15 (24h post last dose) Part B only: Adverse events (AEs): from start of study treatment until follow-up contact; Hematology and Clinical Chemistry: screening, Day 1 predose, Day 7 predose, Day 15 and follow-up visit; Vital signs: Screening, Day 1 (predose, 30 min postdose, 6h postdose), Day 7 predose, Day 15 and follow-up visit; 12-lead ECG: Screening, Day 1 (predose, 30 min postdose, 6h postdose), Day 7 predose, Day 15 and follow-up visit; Pulmonary Function Tests (FEV1): Screening and follow-up visit | — |
Countries
Germany
Contacts
Public ContactGSK Clinical Support Helpdesk
GlaxoSmithKline
Outcome results
None listed