Study B2C111045, A Dose-Finding Study of GW642444 versus Placebo in Patients with COPD

• Conditions: Chronic Pulmonary obstructive Disease (COPD); MedDRA version: 9.1Level: LLTClassification code 10010952Term: COPD

• Registration Number: EUCTR2007-004807-37-EE
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02-25
• Last Update Posted: 14 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 576

Inclusion Criteria

Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Informed Consent: Subjects who give their signed written informed consent to
participate.
2. Gender: Male or females who are 40 - 80 years of age at Visit 1.
A female is eligible to enter and participate in the study if she is of:
Non-child bearing potential (i.e. physiologically incapable of becoming pregnant,
including any female who is post-menopausal); or
Child bearing potential, has a negative pregnancy test at screening, and agrees to
one of the following acceptable contraceptive methods used consistently and
correctly (i.e. in accordance with the approved product label and the instructions of
the physician for the duration of the study – screening to follow-up contact):
• Complete abstinence from intercourse from screening until 2 weeks after the
follow-up contact; or
• Male partner is sterile (vasectomy with documentation of azoospermia) prior to
female subject entry into the study, and this male partner is the sole partner for
that subject; or
• Implants of levonorgestral inserted for at least 1 month prior to the study
medication administration but not beyond the third successive year following
insertion; or
• Injectable progestogen administered for at least 1 month prior to study
medication administration and administered for 1 month following study
completion; or
• Oral contraceptive (combined or progestogen only) administered for at least one
monthly cycle prior to study medication administration; or
• Double barrier method: condom or occlusive cap (diaphragm or cervical/vault
caps) plus spermicidal agent (foam/gel/film/cream/suppository); or
• An intrauterine device (IUD), inserted by a qualified physician, with published
data showing that the highest expected failure rate is less than 1% per year; or
• Estrogenic vaginal ring; or
• Percutaneous contraceptive patches
3. COPD Diagnosis: Subjects with an established clinical history of COPD in
accordance with the following definition by the American Thoracic
Society/European Respiratory Society [Celli, 2004]:
COPD is a preventable and treatable disease characterised by airflow limitation that
is not fully reversible. The airflow limitation is usually progressive and is associated
with an abnormal inflammatory response of the lungs to noxious particles or gases,
primarily caused by cigarette smoking. Although COPD affects the lungs, it also
produces significant systemic consequences.
4. Tobacco Use: Must have current or prior history of at least 10 pack-years of
cigarette smoking. [number of pack years = (number of cigarettes per day / 20) x
number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.
5. Severity of Disease:
• Subjects with a measured post-salbutamol FEV1/FVC ratio of =0.70 at Visit 1
(Screening).
• Subjects with a measured post-salbutamol FEV1 =35 and =70% of predicted
normal values calculated using NHANES III reference equations at Visit 1
(Screening).
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

Subjects meeting any of the following criteria must not be enrolled in the study:
1. Pregnancy: Women who are pregnant or lactating.
2. Asthma: Subjects with a primary diagnosis of asthma. (Subjects with a prior
history of asthma are eligible if COPD is currently their primary diagnosis)
3. a1-antitrypsin deficiency: Subjects with a1-antitrypsin deficiency as the underlying cause of COPD.
4. Other Respiratory disorders: Subjects with active tuberculosis, lung cancer,
bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung
disease or other active pulmonary disease.
5. Lung Resection: Subjects with lung volume reduction surgery within the previous
12 months.
6. Chest X-ray: Chest X-ray (or CT scan) reveals evidence of clinically significant
abnormalities not believed to be due to the presence of COPD. Please view protocol for further information.
7. Hospitalization: Subjects who are hospitalized due to poorly controlled COPD
within 12 weeks of the screening visit.
8. Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the
occurrence of any of the following in the 6 weeks prior to Visit 1:
• acute worsening of COPD that is managed by subject with corticosteroids or
antibiotics, or
• acute worsening of COPD that requires treatment prescribed by a physician
9. Other Diseases/Abnormalities: Subjects with clinically significant cardiovascular
neurological, psychiatric, renal, immunological, endocrine (including uncontrolled
diabetes or thyroid disease) or hematological abnormalities that are uncontrolled.
10. Lower Respiratory Tract Infection: Subjects with lower respiratory tract
infections which required the use of antibiotics within 6 weeks prior to visit 1.
11. 12-Lead ECG: An abnormal and clinically significant 12-lead electrocardiogram
(ECG) that results in an active medical problem. For the purposes of this study, an
abnormal ECG is defined as a 12-lead tracing which is interpreted with (but not
limited to) any of the following: Please view protocol for further information.
• A mean QTc(B) value at screening >450msec, or uncorrected QT>600msec or an
ECG that is not suitable for QT measurements (e.g. poorly defined termination
of the T wave) Please view protocol for further information.
12. Hypertension: Subjects with clinically significant hypertension that is uncontrolled.
13. Hepatitis: Subjects with a positive Hepatitis B surface antigen or positive hepatitis C antibody pre-study or at Screening.
14. Cancer: Subjects with carcinoma that has not been in complete remission for at
least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal
cell carcinoma would not be excluded if the subject was considered cured in less than 5 years since diagnosis.
15. Drug allergy: Subjects with a history of hypersensitivity to any beta-agonist or any component of the MDI and/or nebule or sensitivity to any of the constituents of the dry powder product (magnesium stearate or lactose). In addition patients with a
history of severe milk protein allergy would also be excluded.
16. Drug abuse: Subjects with a known or suspected history of alcohol or drug abuse
within the last 2 years.
17. Medication prior to spirometry: Subjects who are medically unable to withhold
their salbutamol for the 6 hour period required prior to spirometry testing at each
study visit would be ineligible for the study.
18. Additional Medications: The following medications are not permitted during this
study a

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the dose response, efficacy and safety of five dosage regimens of LABA GW642444M with lactose and magnesium stearate (3.0mcg, 6.25mcg, 12.5mcg, 25mcg and 50mcg) in subjects with COPD to inform the selection of doses for use in further clinical studies in this population and other COPD populations.;Secondary Objective: Secondary objectives in this study are to evaluate the population pharmacokinetic profile of GW642444M with lactose and magnesium stearate in COPD patients and to collect blood samples for a pharmacogenetic study.;Primary end point(s): The primary endpoint for this study is the change from baseline in clinic visit trough (prebronchodilator and pre-dose) FEV1 at the end of the 28-day treatment period. The trough FEV1 will be defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28.