A Phase II Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Multicentre Study to Determine the Efficacy and Dose Response of Repeat Inhaled Doses of GW870086X on FEV1 in Adults With Persistent Asthma
Overview
- Phase
- Phase 2
- Intervention
- GW870086 4mg
- Conditions
- Asthma
- Sponsor
- GlaxoSmithKline
- Enrollment
- 136
- Locations
- 1
- Primary Endpoint
- Change from baseline associated with GW870086X versus placebo at Day 28 on FEV1
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This is a randomised, double-blind, placebo-controlled, parallel group study to determine the efficacy of twenty-seven day- repeat inhaled daily doses of GW870086X on forced expiratory volume in 1 second (FEV1). Initially there will be 3 treatment arms; placebo, 2mg GW870086X and 4mg GW870086X. After an interim analysis the trial may; continue to completion using the original doses, be terminated early, or have a fourth arm added of either 1mg GW870086X once daily or 3mg GW870086X once daily.
Detailed Description
This is a randomised, double-blind, placebo-controlled, parallel group study to determine the efficacy of twenty-seven day- repeat inhaled doses of GW870086X on FEV1. GW870086X is a novel inhaled corticosteroid with potent glucocorticoid activity currently in development by GlaxoSmithKline (GSK) as an inhaled treatment of persistent asthma. Initially, subjects will be randomised to receive placebo, 2mg or 4mg GW870086X once daily. An interim analysis will be performed on the primary endpoint to potentially adapt the study design after approximately 45 subjects have completed dosing. Based on the results of the interim analysis, the trial may continue to completion using the original doses or an adaptation to the doses could be made. Either the 1mg GW870086X once daily arm or 3mg GW870086X once daily arm may be added, or the trial could be terminated early. After screening there will be a 4 week run in period prior to start of treatment and after will be a follow up period 1-2 weeks after last dose. Approximately 120 subjects will complete the study. Key safety assessments include; clinical laboratory tests, vital signs and collection of adverse events (AE's).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female between 18 and 65 years
- •A female subject is eligible to participate if she is of: Non-childbearing potential. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
- •Male subjects must agree to use one of the protocol contraception methods.
- •Body weight, men ≥ 50 kg, women ≥ 45 kg and BMI within the range 18.5 - 29.0 kg/m2 (inclusive).
- •Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with intermittent short-acting beta-2 agonist therapy
- •Severity of Disease: A best FEV1 of 60%-85% of the predicted normal value during the Visit 1 screening period.
- •No history of smoking within 6 months of the start of the study and with a total pack year history of ≤10 pack years
- •Capable of giving written informed consent
- •Single QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.
- •AST and ALT \< 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
Exclusion Criteria
- •A positive test for Hepatitis B or Hepatitis C antibody.
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities
- •The subject has a positive pre-study drug/alcohol screen unless a positive can be explained by the patients' medication.
- •Past or present disease, which as judged by the investigator, may affect the outcome of this study.
- •Clinically significant abnormalities in safety laboratory analysis at screening, as determined by the investigator.
- •Subject is hypertensive at screening.
- •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.
- •Administration of oral, injectable or dermal steroids within 8 weeks of screening.
- •Exacerbation of asthma within 4 weeks prior to the first dose of study medication.
- •Respiratory Infection that is not resolved within the 4 weeks before screening and led to a change in asthma management, or in the opinion of the Investigator is expected to affect the subjects asthma status or the subjects ability to participate in the study.
Arms & Interventions
GW870086 4mg
GW870086 4mg once daily in the morning for 27 ± 2 days
Intervention: GW870086 4mg
GW870086 2mg
GW870086 2mg once daily in the morning for 27 ± 2 days
Intervention: GW870086 2mg
Placebo
Placebo once daily in the morning for 27 ± 2 days
Intervention: GW870086 Placebo
GW870086 1mg
GW870086 1mg once daily in the morning for 27 ± 2 days
Intervention: GW870086 1mg
GW870086 3mg
GW870086 3mg once daily in the morning for 27 ± 2 days
Intervention: GW870086 3mg
Outcomes
Primary Outcomes
Change from baseline associated with GW870086X versus placebo at Day 28 on FEV1
Time Frame: Day 28
Secondary Outcomes
- Rescue medication usage(Days 1-28)
- Change from baseline in FEV1 on Day 7, Day 14 and Day 21(Days; 7, 14, 21)
- Change from baseline in peak expiratory flow rate (PEFR) measured twice daily over 28 days(Days 1-28)
- Assessment of vital signs, safety laboratory parameters and incidences of adverse events throughout treatment period(9-10 weeks)