A randomised, double-blind, placebo-controlled, dose ascending, 3 period crossover study to examine the safety, tolerability, pharmacodynamics and pharmacokinetics of repeat inhaled doses of GSK233705B in COPD subjects.

• Conditions: Study is in COPD patients

• Registration Number: EUCTR2006-001419-30-BE
• Lead Sponsor: GlaxoSmithKline Research and Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-06-26
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

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

Inclusion Criteria

1. Men or women who are between 40 and 75 years of age
2. Female subjects must be of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophrectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
3. Male subjects must agree to abstain from or use a condom during sexual intercourse with pregnant or lactating females; or unwillingness of male subjects to use a condom/spermicide, in addition to having their female partner use another form of contraception, such as an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation, if engaging in sexual intercourse with a female partner who could become pregnant. This criterion must be followed from the time of the first dose of study medication until 84 days after the last dose of study medication.
4. Subject diagnosed with COPD, as defined by the GOLD guidelines.
5. Body weight = 50kg
6. Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years
(1 pack year = 20 cigarettes smoked per day for 1 year or equivalent).
7. Subject has FEV1/FVC < 0.7 post-bronchodilator (salbutamol).
8. Subject has FEV1 = 80% of predicted normal for height, age and gender after inhalation of 200 µg salbutamol.
9. Response to ipratropium bromide defined as:
• Either: An increase in FEV1 of =12% and =150 mL at 2 h following inhalation of 80 µg of ipratropium bromide at the screening visit
• or: a documented increase in FEV1 of =12% and =150 mL at 2 h following inhalation of 80 µg of ipratropium bromide within 6 months of screening and an increase in FEV1 of >6% and >100ml 2h following inhalation of 80 µg of ipratropium bromide 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).
10. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
11. Subject is available to complete all study measurements and procedures.
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

1. Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, may affect the outcome of this study.
2. The subject has a positive pre-study urine drug/ urine alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
3. History of alcohol/drug abuse or dependence within 12 months of the study: Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
4. The subject has a positive pregnancy test.
5. Subject has FEV1 ¡Ü 40% of predicted after inhalation of salbutamol.
6. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
7. The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug(whichever is longer) prior to the first dose of current study medication.
8. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
9. Where participation in study would result in donation of blood in excess of 500 mL within a 56 day period
10. The subject has donated a unit of blood within 30 days of screening, or, intends to donate during the study.
11. Subject has claustrophobia that may be aggravated by entering the plethysmography cabinet.
12. The subject has a known allergy or hypersensitivity to ipratropium bromide, tiotropium bromide, atropine and any of its derivatives or milk protein/lactose.
13. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation
14. Subject is unable to use the DISKUS™ device correctly.
15. Subject has prostate hypertrophy or narrow angle glaucoma.
16. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John'sWort) 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 sponsor the medication will not interfere with the study procedures or compromise subject safety

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and tolerability of repeat inhaled doses of GSK233705B (inhaled twice daily for 7 days) in COPD patients.;Secondary Objective: To determine the duration and extent of bronchodilation of repeat doses following inhaled GSK233705B (inhaled twice daily for 7 days) in COPD patients.<br>To assess the pharmacokinetics of GSK233705 following repeat inhaled doses (inhaled twice daily for 7 days) in COPD patients.<br>;Primary end point(s): • General safety and tolerability endpoints: adverse events, blood pressure, heart rate, 12-lead ECG, Holter and Lead II ECG monitoring, lung function and clinical laboratory safety tests.<br>• The following endpoints will be derived for the supine Vital Signs (heart rate, systolic and diastolic blood pressure) and the supine ECG parameters QTc (F) and QTc (B) <br>- Maximum value (0-4 hour) for the morning dose<br>- Weighted Mean (0-4 hour) for the morning dose<br>