A randomised, double blind, placebo-controlled, double dummy, 4-way cross-over, dose ascending study to assess the safety, tolerability, pharmacodynamics and pharmacokinetics of single inhaled doses of GSK573719 (250, 500 and 1000µg) and tiotropium bromide (18µg) via DPI in COPD patients.

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

• Registration Number: EUCTR2007-000187-25-DE
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-08
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Caucasian male or female subjects aged 40-75 years inclusive. The need to recruit only Caucasian subjects is related to the need to rigorously exclude 2D6 poor metabolisers based on genotype.
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.An established clinical history of COPD (ATS/ERS definition). Established clinical history of COPD in accordance with the following definition by the American Thoracic Society/European Respiratory Society (ATS/ERS) [Celli, 2004].
‘Chronic obstructive pulmonary disease (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.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).
5.Subject has FEV1/FVC < 0.7 post-bronchodilator (salbutamol) dose.
6.Subject has 40 ? FEV1 ? 80% of predicted normal for height, age and gender after inhalation of salbutamol dose.
7.Response to ipratropium bromide defined as:
•an increase in sGaw of ?25% over pre-dose baseline at 2 h following 80?g ipratropium bromide; or
•a documented increase in sGaw of =25% over pre-dose baseline at 2 h following inhalation of 80 µg of ipratropium bromide within 3 months of screening.
8.Subject is able and has given written informed consent to take part in the study.
9.Subject is available to complete all study measurements and procedures.
10.Subject’s BMI is 18.0 – 32.0 kg/m2.
11.Subjects have a 24hr Holter recording that is within normal limits and does not demonstrate any clinically important abnormality that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years)
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Subjects who have a past or present disease of any organ system, which as judged by the Investigator, may affect the outcome of this study.
2.The subject has a positive pre-study drug screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cannabis, Cocaine and Opiates. The detection of drugs with a legitimate medical use would not be an exclusion to study participation.
3.The subject has a positive pre-study alcohol screen. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
4.A suspected history of alcohol abuse within the six months previous to the screening visit.
5.The subject has tested positive for hepatitis C antibody, hepatitis B surface antigen or HIV (if determined by local SOP’s).
6.Subject has received an investigational drug within 30 days of screening.
7.The subject is currently taking medication which is known to be a CYP 2D6 inhibitor/substrate.
8.The subject has donated a unit (400ml) of blood within 60 days of screening, or, intends to donate during the study.
9.The subject has a known allergy or hypersensitivity to ipratropium bromide, tiotropium bromide, atropine and any of its derivatives or lactose/milk protein.
10.Subject is unable to use the DISKUS™/HandiHaler devices correctly.
11.Subject has prostatic hypertrophy, bladder outlet obstruction, or narrow angle glaucoma.
12.Subjects with a 2D6 poor metaboliser genotype (Caucasian).
13.The subject has claustrophobia that may be aggravated by entering the plethysmography cabinet (American Association of Respiratory Care 2001 guidelines for body plethysmography)
14.Received antibiotic therapy for either a lower respiratory tract infection or for COPD exacerbation within the 4 weeks prior to Screening.

Study & Design

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