A Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Repeat-Dose study to evaluate the Efficacy and Safety of Intravenous GSK679586 in Patients with Severe Asthma

• Conditions: Severe asthma; MedDRA version: 9.1Level: LLTClassification code 10003553Term: Asthma

• Registration Number: EUCTR2008-004149-27-GB
• Lead Sponsor: GlaxoSmithKline Research and Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10-18
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

1. Male or female between 18 and 75 years of age (inclusive). 2. A female subject is eligible to participate if she is of: • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea, view protocol for further information. • Child-bearing potential (only applicable for sites where regulation allows for their inclusion) and agrees to use one of the contraception methods listed in Section 7.1. Acceptable contraception is required by WCBP for one month prior to screening, during the course of the study and for 18 weeks after the last dose of study drug. 3. Male subjects must agree to use one of the contraception methods listed in Section 7.1 from administration of the first dose, during the course of the study and 18 weeks after the last dose of study drug. Since stage-dependent evaluation of spermatogenesis has not yet been completed, 18 weeks of male contraception after the last dose of study drug will be enforced for the time being. This requirement may be changed in light of the emerging spermatogenesis data. 4. BMI within the range 19 – 35 kg/m2 (inclusive). 5. Subjects who have been diagnosed with asthma for = 6 months (according to GINA 2007 Guidelines) requiring regular treatment with inhaled corticosteroid (ICS) = 500 µg/day fluticasone or equivalent. Patients also taking long-acting ß-agonists are eligible provided they meet the other inclusion criteria. 6. Subjects must have been on a stable dose of = 500 µg/day fluticasone or equivalent for = 4 weeks before screening. This requires that there have been no changes to the asthma medication in the 4 weeks prior to Visit 1 and in the period between Visit 1 & Visit 1a (if performed) and Visit 1a and Visit 1b (if performed). Subjects will be permitted to remain on all other concomitant asthma medication (with the exception of omalizumab) throughout the study. 7. Subjects on regular OCS as maintenance treatment for their asthma, whose usual long term daily maintenance dose is a maximum of 25 mg prednisolone can be included in the study. Subjects may have their maintenance dose varied up to a maximum daily dose of 30 mg prednisolone or equivalent, and down to a minimum daily dose of 5 mg prednisolone or equivalent during the 4 weeks prior to screening and throughout the study, providing these variations do not result in their usual long term daily maintenance dose being higher that 25mg prednisolone per day. 8. Baseline (pre-bronchodilator) FEV1 35-80% predicted at screening. 9. Subjects must demonstrate reversible airways disease as indicated by an increase of FEV1 =12% from baseline within 30 minutes (±5 minutes) of inhaled salbutamol or albuterol via a metered dose inhaler with or without spacer or 30 minutes after nebulised salbutamol or albuterol. Subjects must have abstained from using all bronchodilator therapy prior to assessment of their pulmonary function (i.e. withdrawal from long-acting betaagonist treatment for = 12 hours, short-acting ß-agonist treatment for = 6 hours and long-acting anti-cholinergic treatment for = 72 hours prior to Visit 1, 1a or 1b). A second test of ß-agonist reversibility will be permitted at Visit 1a if the subject does not meet this entry criterion at Visit 1. A third test of ß-agonist reversibility will be permitted at Visit 1b if the subject does not meet this entry criterion at Visit 1a. 10. Subjects must be symptomatic at scree

Exclusion Criteria

1. History of regular alcohol consumption within 6 months of the study defined as: • For European sites: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine. • For US sites: an average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits. 2. Acute asthma exacerbation requiring hospitalization for >48 hours within 3 months prior to screening. 3. Discharge from hospital following endotracheal intubation for asthma-related exacerbation within the past 6 months. 4. Respiratory illness within 4 weeks of screening. 5. Current or recent lower respiratory tract infection (resolved less than 6 weeks from screening). 6. History of recurrent lower respiratory tract infection (more than 3 in the three months prior to screening) requiring antibiotics 7. Presence of other respiratory disease or chronic pulmonary condition other than asthma that is uncontrolled with standard treatment and in the opinion of the Investigator and/or the Medical Monitor participation could present a risk to the patient. 8. A mean QTc(B) or QTc(F) value at screening >450msec taken from assessments in triplicate, or an ECG that is not suitable for QT measurements (e.g. Left bundle branch block or poorly defined termination of the T wave). 9. The subject has taken methotrexate, troleandomycin, oral gold, cyclosporin, or any other experimental anti-inflammatory therapies within 3 months of screening 10. The subject has used omalizumab within 4 months of treatment (Visit 4) 11. Treatment with an investigational drug within 30 days or five half-lives or twice the duration of the biological effect of the investigational product (whichever is longer), prior to the screening visit (Visit 1) (this includes investigational formulations of marketed products). 12. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 13. A usual daily maintenance dose of prednisolone (or equivalent) of >25 mg/day within 4 weeks before the screening visit (Visit 1). 14. Live/attenuated vaccinations within 4 weeks of screening (Visit 1) or during the study 15. The subject has clinically significant cardiovascular, neurological, renal, endocrine, gastrointestinal, hepatic, or haematologic abnormalities that are uncontrolled with standard treatment and in the opinion of the Investigator and/or the Medical Monitor their participation could present a risk to the patient. 16. The subject has abnormal laboratory values considered by the Investigator to be clinically significant that could present a risk to the patient, specifically patients with alanine aminotransferase or aspartate transaminase values greater than 1.5 x the upper limit of normal. 17. The subject has a history (or suspected history) of alcohol misuse or substance abuse. 18. The subject has a known immunodeficiency disorder. 19. The subject is unable to follow study instructions such as dosing directions, study diary completion, use of the peak flow meter or use of a metered dose inhaler. 20. The subject has a gastrointestinal or respiratory pa

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified