A study to test the effectiveness and safety of inhaled GSK2269557 – a potential new medicine for asthma.
- Conditions
- AsthmaMedDRA version: 18.1Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2014-003808-77-DE
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 50
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
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 <35%).
6. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
7. QTc > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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<br>To characterise the clinical response of inhaled GSK2269557 administered once daily for 28 days in subjects with persistent uncontrolled asthma, compared with placebo.<br><br>Safety<br>To assess the safety and tolerability of inhaled GSK2269557 administered once daily for 28 days in subjects with persistent uncontrolled asthma, compared with placebo.<br><br>Pharmacokinetics<br>To evaluate the plasma pharmacokinetics of inhaled GSK2269557 administered once daily for 28 days in subjects with persistent uncontrolled asthma.<br>;Primary end point(s): Change from baseline in trough FEV1 at Day 28;Timepoint(s) of evaluation of this end point: Day 28
- Secondary Outcome Measures
Name Time Method