Dose ranging study for GSK233705B delivered once daily insubjects with COPD.

• Conditions: Chronic Obstructive Pulmonary (COPD) disease

• Registration Number: EUCTR2007-006287-29-NL
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05-29
• Last Update Posted: 9 October 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1. Informed Consent: A signed and dated written informed consent prior to study
participation.

2. Gender: Male or female adults.
A female is eligible to enter and participate in this study if she is of:
a. non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post-menopausal; or,
b. child-bearing potential, has a negative pregnancy test at Visit 1/Visit 1A, 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 through follow-up contact):
• Complete abstinence from intercourse from Screening until 2 weeks after the
follow-up contact
• Oral contraceptive (either combined or progestogen alone) administered for at
least 1 monthly cycle prior to study medication administration
• Injectable progestogen administered for at least 1 month prior to study
medication administration and administered for 1 month following study
completion
• Implants of levonorgestrel inserted for at least 1 month prior to the study
medication administration but not beyond the third successive year following
insertion
• Estrogenic vaginal ring
• Percutaneous contraceptive patches
• Intrauterine device (IUD) or intrauterine system (IUS) with published data
showing that the highest expected failure rate is less than 1% per year
• Male partner sterilization (vasectomy with documentation of azoospermia) prior
to the female subject’s entry into the study, and this male is the sole partner for
that subject
• Double barrier method: condom or occlusive cap (diaphragm or cervical/vault
caps) plus spermicidal agent (foam/gel/film/cream/suppository)

3. Age: 40 to 80 years of age at Visit 1

4. Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004] as follows: Chronic obstructive pulmonary disease is a preventable and treatable disease state characterized 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.

5. Current or previous cigarette smokers with a history of cigarette smoking of = 10 pack-years [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.

6. Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of =0.70 and a
post-albuterol/salbutamol FEV1 of = 35 and =70% of predicted normal values
calculated using NHANES III reference equations at Visit 1/Visit 1A (Screening) [Hankinson, 1999].
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Women who are pregnant or lactating.

2. A current diagnosis of asthma.

3. Known respiratory disorders other than COPD including but not limited to a-1 antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease.

4. Any previous lung resection surgery (e.g., lung volume reduction surgery or lobectomy).

5. Chest X-ray or computed tomography (CT) scan which reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken if a chest X-ray or CT scan is not available within 6 months prior to Visit 1. For subjects in Germany, if a chest X-ray (or CT scan) is not available in the 6 months prior to Visit 1, the subject will not be eligible for the study.

6. Use of oral corticosteroids or antibiotics for COPD within 6 weeks prior to Visit 1.

7. Hospitalization: Hospitalization for COPD or pneumonia within 3 months prior to
Visit 1.

8. Use of antibiotics for a lower respiratory tract infection within 30 days prior to Visit 1.

9. Other Diseases/Abnormalities: Clinically significant and uncontrolled
cardiovascular, neurological, psychiatric, renal, gastro-intestinal, immunological,
endocrine (including uncontrolled diabetes or thyroid disease) or hematological
abnormalities.

10. 12-Lead ECG: An abnormal and clinically significant 12-lead electrocardiogram
(ECG) that results in 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:
i. Clinically significant conduction abnormalities (e.g., left bundle branch block,
Wolff-Parkinson-White syndrome)
ii. Myocardial ischemia
iii. Clinically significant arrhythmias (e.g., atrial fibrillation, ventricular tachycardia)
iv. A mean QTc(B) value at screening >450msec, the QTc(B) of all 3 screening
ECGs are not within 10% of the mean, or an ECG that is not suitable for QT
measurements (e.g. poorly defined termination of the T wave)
The independent cardiologist, contracted by GSK, will determine the clinical
significance of any ECG abnormality and determine if a subject is precluded from
entering the study.

11. Hepatitis: A positive Hepatitis B surface antigen or positive hepatitis C antibody at Visit 1.

12. Cancer: A current malignancy or previous history of cancer in remission for < 5
years prior to Visit 1 (localized basal cell or squamous cell carcinoma of the skin that
has been resected is not exclusionary).

13. A history of allergy or hypersensitivity to ipratropium, tiotropium, or atropine and any of their derivatives, lactose/milk protein or magnesium stearate.

14. Diseases Preventing Use of Anticholinergic: 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 anticholingeric.

15. Medication Prior to Spirometry: Medically unable to withhold their albuterol/salbutamol for the 6 hour period required prior to spirometry testing at each study visit or to withhold ipratropium (if applicable) for the 6-hour period prior to
Visit 1/Visit 1A, Visit 2, and Visit 3.

16. Additional Medications: Unable to stop medications at the defined times prior to Visit 1 (please refer to page 24 of the protocol).

17. Use of inhaled corticosteroids at a dose greater than 1000 mcg/day o

Study & Design

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