A randomised, double-blind, crossover study to investigate the bronchodilatation post-inhalation of GSK961081 alone and with the addition of cumulative doses of short acting bronchodilators (salbutamol and ipratropium bromide) in patients with COPD

• Conditions: Chronic Obstructive Pulmonary Disease

• Registration Number: EUCTR2008-000725-18-GB
• Lead Sponsor: GlaxoSmithKline Reaseach & Development

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02-22
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Subject is male or female (of non-child bearing potential) = 40 years of age and = 75 years of age.
Non- child bearing potential is defined as physiologically incapable of becoming pregnant, including females who are post-menopausal (more than 2 years without
menses with appropriate clinical history i.e. age, history of vasomotor symptomsestradiol and FSH levels may be checked if indicated) and females who are
surgically sterile (hysterectomy, tubal ligation or bilateral oophorectomy).
2. Subject diagnosed with COPD in accordance with ATS/ERS guidelines.
3. Subject is a smoker or an ex-smoker with a history of at least 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent)
4. Subject has FEV1/FVC < 0.7 post-bronchodilator (salbutamol)
5. Subject has FEV1 < 80 % of predicted normal for height, age, gender after inhalation of salbutamol
6. Response to ipatropium bromide defined as:
Either an increase in FEV1 of > 12 % and > 150 mL within 2 hours following
inhalation of 80 µg ipratopium bromide (Atrovent MDI via spacer) at the screening
visit
Or: a documented increase in FEV1 of >12 % and > 150 mL within 2 hours
following inhalation of 80 µg ipratopium bromide within 6 months of screening and
an increase in FEV1 of > 6 % and > 100 mL within 2h following inhalation of 80 µg
ipratopium bromide (Atrovent MDI via spacer) at the screening visit (in order to
allow for potential fluctuations in the response to ipratropium bromide in patients
known to be responders to ipratropium bromide)
7. Response to salbutamol defined as:
Either an increase in FEV1 of > 12 % and > 150 mL within 2 hours following
inhalation of 400 µg salbutamol MDI (via spacer) at the screening visit
Or: a documented increase in FEV1 of >12 % and > 150 mL within 2 hours
following inhalation of 400 µg salbutamol MDI within 6 months of screening and an
increase in FEV1 of > 6 % and >100 mL within 2h following inhalation of 400 µg
salbutamol MDI (via spacer) at the screening visit (in order to allow for potential
fluctuations in the response to salbutamol in patients known to be responders to
salbutamol)
8. Body mass index (BMI) within the range 18-35 kg/m2
9. Subject is able and willing to give written informed consent to take part in the study.
10. Subject is available to complete all study assessments
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria
apply:
1. Subjects who have a past or present disease, which as judged by the Investigator and medical monitor may affect the outcome of the study or the safety of the subject
2. Subjects with clinically relevant findings on laboratory safety tests.
3. Women who are pregnant or lactating
4. An unwillingness of subjects to abstain from sexual intercourse with pregnant or
lactating women; or an unwillingness of the subject to use a condom/spermicide in
addition to having their female partner use another form of contraception such as
IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone,
subdermal implants or tubal ligation if the woman could become pregnant from the
time of the first dose study medication until 90 days post-dose
5. The subject has a positive urine drugs of abuse screen.
6. A history, or suspected history, of alcohol abuse within the 6 months before the
screening visit.
7. A positive test for hepatitis C antibody, hepatitis B surface antigen, or HIV.
8. The subject has participated in a clinical study with another New Chemical Entity
within the past 2 months or participated in a clinical study with any other drug during
the previous month.
9. The subject has donated a unit of blood within the 56 days of dosing or intends to
donate within 56 days after completing the study.
10. Subject has an FEV1 < 40 % of predicted for age, height and gender after inhalation of salbutamol.
11. The subject has a diagnosis of active tuberculosis, lung cancer, sarcoidosis,
bronchiectasis, lung fibrosis, pulmonary hypertension or with a primary diagnosis of
asthma
12. The subject has a known allergy or hypersensitivity to ipratropium bromide,
salbutamol, or lactose
13. A subject in whom ipratropium bromide or salbutamol is contraindicated
14. Subjects with lung volume reduction surgery within 12 months of screening
15. Poorly controlled COPD as defined in the protocol
16. Subject has had a respiratory tract infection in the 4 weeks before screening
17. Subject requires treatment with inhaled cromolyn sodium, theophyline, oral ß2-
agonists, nebulised anticholinergics or leukotriene antagonists
18. Subject is unable to abstain from long acting ß2-agonist from 72 hours before
screening and throughout the dosing period
19. Subject is unable to abstain from tiotropium bromide from 28 days before screening and throughout the dosing period
20. Subject is predicted to be unable to abstain from short acting inhaled ß2-agonists or short acting antimuscarinics for 6 hours before screening and for 6 hours before dosing with GSK961081 until all post-dose lung function tests have been completed for a given study day.
21. Subject has received oral corticosteroids within the 6 weeks before screening
22. Subject is receiving > 1000 µg FP (or equivalent) a day of inhaled corticosteroid or has changed dose within the 6 weeks before screening or is predicted not to be able to maintain a constant dose during the study
23. Subject is receiving oxygen therapy or nocturnal positive pressure treatment
24. Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator would prevent use of an inhaled anticholinergic
25. The subject is unable to use the dosing devices (MDPI/ MDI/ spacer) correctly.
26. Subject with carcinoma that has not been in complete remission for at least 5

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 pulmonary pharmacodynamic profile of single doses of GSK961081 alone and in combination with cumulative doses of short acting bronchodilators (salbutamol and ipratropium bromide) in COPD patients.;Secondary Objective: To assess the systemic pharmacodynamics of single doses of GSK961081 in combination with cumulative doses of short acting bronchodilators (salbutamol and ipratropium bromide) as measured by heart rate, 12-lead ECG including QTc(B) and QTc (F), blood pressure, serum potassium and blood glucose in COPD patients.<br><br>To assess the systemic pharmacokinetics of single doses of GSK961081 in combination with cumulative doses of short acting bronchodilators (salbutamol and ipratropium bromide) in COPD patients.;Primary end point(s): Maximal increase from pre-dose short-acting bronchodilator (salbutamol or ipratropium bromide) in FEV1 after inhalation of short-acting bronchodilator at 1h, 12h and 24h.