A Study in Asthmatics to Determine the Efficacy and Dose Response of Repeat Doses of GW870086X on Forced Expiratory Volume in 1 Second (FEV1)

• Status: Completed
• Trial end date: 2011-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline

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.

• Any asthma exacerbation requiring oral corticosteroids within 8 weeks of screening. A subject must not have had any hospitalisation for asthma within 6 months prior to screening

• A positive test for HIV antibody.

• History of regular alcohol consumption within 6 months of the study.

• 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).

• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• Use of prescription or non-prescription drugs within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Paracetamol is an exception and will be permitted at daily doses of up to 4 g from screening to follow-up.

• Has taken Xanthines (including theophylline, but not including caffeine), anticholinergics, cromoglycates and/or long-acting beta-2 agonists within 1 week prior to screening and is unable to abstain from them throughout the study.

• Unable to abstain from other medications other than short acting inhaled beta-2 agonists and paracetamol (up to 4 g per day) 7 days before screening until the follow-up visit.

• Unable to abstain from medication or supplements that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, from screening and throughout the study.

• Unable to use the DISKHALER® device correctly.

• History of sensitivity to any of the study medications.

• Where participation in the study would result in donation of blood or blood products in excess of 500 ml within a 56 day period.

• Unwillingness or inability to follow the procedures outlined in the protocol.

• The subject is not able to understand or comply with protocol requirements, instructions and protocol stated restrictions.

• Vulnerable subjects.

• Subject is mentally or legally incapacitated.

• Urinary cotinine levels indicative of smoking or history within 6 months prior to screening.

• Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.