Asthma MedDRA version: 18.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: GSK2269557 DISKUS™ Inhalation Powder
Product Code: GSK2269557
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Not available
CAS Number: 1364799-98-3
Current S
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Between 18 and 70 years of age inclusive, at the time of signing the informed consent. 2. Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with an intermittent SABA or other non-corticosteroid controllers. Non corticosteroid controllers (e.g. leukotriene receptor antagonists; LTRAs) must be discontinued from Screening until the end of Treatment Period 2. 3. Able to replace current SABA treatment with salbutamol Metered Dose Inhaler (MDI) at Screening for use as needed for the duration of the study. Judged capable of withholding salbutamol for at least 4 hours prior to FEV1 assessments. 4. No use of an ICS or LABA for at least 12 weeks prior to first dose of study medication. 5. A best pre-bronchodilator FEV1 = 60% of the predicted normal value at Screening. Predicted values will be based upon [Quanjer, 2012]. 6. FEV1 increase by =12% and = 200 mL over baseline value within 10-40 minutes of inhalation of 400 mcg salbutamol MDI (a spacer device may be used if required). 7. Positive skin prick test to common aero-allergen(s) at screening (not historical). 8. Sputum sub-study only: Able to produce > 100 mg of sputum at Screening or during the Run-in Period. 9. Body weight =45 kg and body mass index (BMI) within the range 18–32 kg/m2 (inclusive) 10. Male subject. Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the first dose of study medication until completion of the follow-up visit. a. Vasectomy with documentation of azoospermia. b. Male condom plus partner use of one of the contraceptive options below. • Contraceptive subdermal implant with a <1% rate of failure per year, as stated in the product label • Intrauterine device or intrauterine system with a <1% rate of failure per year, as stated in the product label • Oral contraceptive, either combined or progestogen alone • Injectable progestogen • Contraceptive vaginal ring • Percutaneous contraceptive patches 11. 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: a. 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 [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. b. 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 medicat
Exclusion criteria
Exclusion criteria: 1. History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures. 2. Any severe asthma exacerbation, defined as deterioration of asthma requiring the use of systemic corticosteroids (oral, parenteral or depot) within 12 weeks of Screening, or an inpatient hospitalisation or emergency department visit due to asthma that required systemic corticosteroids within 6 months of Screening. 3. Respiratory Infection: culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that has not resolved within 4 weeks of Screening and led to a change in asthma management or, in the opinion of the investigator, is expected to affect the subject’s asthma status or the subject’s ability to participate in the study. 4. Concurrent Respiratory Disease: current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, lung cancer, or other respiratory abnormalities other than asthma. 5. ALT >2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 450 msec or QTc > 480 msec in subjects with Bundle Branch Block. NOTES: Based on the averaged QTc values of triplicate ECGs obtained over a brief recording period (e.g. 5–10 minutes) The QTc is the QT interval corrected for heart rate according to Bazett’s formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machine-read or manually over-read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. Several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial. For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used, as specified in the Reporting and Analysis Plan (RAP). 8. Other Laboratory Abnormalities or Concurrent Diseases/Clinical: clinically significant laboratory abnormality, uncontrolled condition or disease state that, in the opinion of the investigator (in consultation with the GSK Medical Monitor, if required), would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study. 9. Use of any of the prohibited medications listed in Table 4 (Section 6.12.2). 10. Current smokers or subjects with a history of smoking within 6 months of Screening, or with a total pack year history of >5 pack years or those subjects using a nicotine replacement or containing product within 5 half-lives of the first dose of study medication in the current study. 11. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 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 spi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy of inhaled GSK2269557 administered once daily for 28 days in subjects with persistent uncontrolled asthma, compared with placebo.;Secondary Objective: Efficacy To characterise the clinical response of inhaled GSK2269557 administered once daily for 28 days in subjects with persistent uncontrolled asthma, compared with placebo. Safety To assess the safety and tolerability of inhaled GSK2269557 administered once daily for 28 days in subjects with persistent uncontrolled asthma, compared with placebo. Pharmacokinetics To evaluate the plasma pharmacokinetics of inhaled GSK2269557 administered once daily for 28 days in subjects with persistent uncontrolled asthma. ;Primary end point(s): Change from baseline in trough FEV1 at Day 28;Timepoint(s) of evaluation of this end point: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Weighted mean (0-4 hours) FEV1 at Day 28 2.Change from baseline in trough FEV1 at Day 7 and Day 14 3. Change from baseline in FVC at Day 7, Day 14 and Day 28 4. Change from baseline in FEV1/FVC at Day 7, Day 14 and Day 28 5.Change from baseline in Asthma Control Test (ACT) score at Day 28 6.Change from baseline in daily FEV1 (AM) and PEF (AM and PM) averaged over the treatment period 7.Change from baseline in trough FeNO at Day 7, Day 14 and Day 28 8.Mean number of inhalations per day of rescue medication (salbutamol) and percentage of rescue free days over the treatment period 9.Adverse Events 10.Haematology and Clinical Chemistry 11.Vital signs 12.12-lead ECG 13.Trough plasma concentration after 7 days, 14 days and 28 days of treatment 14.Day 28 plasma exposure up to 3.5 hours post dose ;Timepoint(s) of evaluation of this end point: 1.0–4 h on Day 28 2.pre-dose Day 7 and pre-dose Day 14 3.Pre-dose Day 28 4.daily morning FEV1 (Day 1 to Day 28) and daily morning and evening PEF (Day 1 to Day 28) 5.pre-dose Day 7, Day 14 and Day 28 6.Day 1 to Day 28 7.Day 1, Treatment Period 1 to Follow-up 8.Screening to Day 28, Treatment Period 2 9.Screening to Follow-up 10.Screening to Day 28, Treatment Period 2 11.pre-dose Day 7, Day 14 and Day 28 12.Day 28 pre-dose, and Day 28 5 to 10 minutes post-dose and 2.5 to 3.5 hours post-dose | — |
Countries
Germany
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed