Safety Study Using GSK233705 And Tiotropium In Patients With Chronic Obstructive Pulmonary Disease

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Randomised, Double Blind, Placebo-controlled, Double Dummy, 4-way Cross-over, Dose Ascending Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Inhaled Doses of GSK233705 and Tiotropium Bromide (18µg) Via DPI in COPD Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00279019
• Other study ID #: AC2103473
• Status: Completed
• Phase: Phase 1
• First received: January 17, 2006
• Last updated: September 21, 2017
• Start date: December 12, 2005
• Est. completion date: June 13, 2006

Study information

• Verified date: September 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

GSK233705 is a high-affinity specific muscarinic receptor (mAChR) antagonist which is being developed for once daily treatment of chronic obstructive pulmonary disease (COPD). The long duration of action of GSK233705 when administered via inhalation in animal models supports the potential for use as a once-daily bronchodilator for chronic obstructive pulmonary disease.

GSK233705 is a high-affinity specific muscarinic receptor (mAChR) antagonist which is being developed for once daily treatment of chronic obstructive pulmonary disease (COPD). The long duration of action of GSK233705 when administered via inhalation in animal models supports the potential for use as a once-daily bronchodilator for chronic obstructive pulmonary disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: June 13, 2006
• Est. primary completion date: June 13, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion criteria:

• Of non-childbearing potential.

• Diagnosed with COPD, as defined by the GOLD guidelines.

• Smoker or an ex-smoker with a smoking history of at least 10 pack years.

• FEV1/FVC < 0.7 post-bronchodilator (salbutamol).

• FEV1 <= 80% of predicted normal for height, age and gender after inhalation of salbutamol.

• Response to ipratropium bromide 9.

• Subject's weight is 60kg.

Exclusion criteria:

• Past or present disease, which as judged by the Investigator and the Medical Monitor, may affect the outcome of this study.

• FEV1 <=50% of predicted after inhalation of salbutamol.

• Tested positive for hepatitis C antibody, hepatitis B surface antigen or HIV.

• Has claustrophobia that may be aggravated by entering the plethysmography cabinet.

• Has prostate hypertrophy or narrow angle glaucoma.

• Diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, allergic rhinitis, or asthma.

• Poorly controlled COPD.

• Participated in a Pulmonary Rehabilitation Program within 4 weeks prior to screening visit or will enter a program during the study.

• Had a respiratory tract infection in the 4 weeks prior to the screening visit and throughout the duration of the study.

• History of congestive heart failure, coronary insufficiency or cardiac arrhythmia.

• A mean QTc(B) value at screening >440msec, the QTc(B) of all 3 screening ECGs are not within 10% of the mean, a PR interval outside the range 120-210msec or an ECG that is not suitable for QT measurements.

• A history of elevated supine blood pressure or a mean blood pressure equal to or higher than 160/95 mmHg.

• A mean heart rate outside the range 40-90 bpm.

• QTc prolongation >470msec or risk factors for torsades de pointes (heart failure NYHA II-IV, hypokalaemia, familial long QT syndrome).

• Receiving co-medication with drugs which prolong the QTc interval.

• Requires treatment with inhaled cromolyn sodium or nedocromil, oral beta-2-agonists, nebulised beta-2-agonists, nebulised anticholinergics or leukotriene modifiers.

• Unable to abstain from xanthines (other than caffeine.

• Unable to abstain from short-acting inhaled bronchodilators.

• Unable to abstain from long-acting inhaled bronchodilators.

• Changed dose of inhaled or oral corticosteroids within the last 6 weeks.

• Taking more than 10mg/day of prednisolone (or equivalent).

• Receiving treatment with long term or short-term oxygen therapy or requires nocturnal positive pressure for sleep apnea.

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
• Tiotropium
Tiotropium will be given orally as overfoiled strips of 5 capsules, each containing 18 micrograms of tiotropium (as bromide monohydrate) administered via a HandiHaler device.
• Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Grosshansdorf	Schleswig-Holstein
Germany	GSK Investigational Site	Hannover	Niedersachsen

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events, blood pressure, heart rate, 12-lead electrocardiogram (ECG), Holter and Lead II ECG monitoring, ECG, lung function and clinical laboratory safety tests.		Up to Week 12
Secondary	Plasma and urine concentrations of GSK233705 and derived pharmacokinetic parameters. Serial IOS and FEV1 measurements over 27 hours post-dose Serial sGaw, Raw measurements over 24 hours post-dose.		Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours Post-dose

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
•   Results for study AC2103473 can be found on the GSK Clinical Study Register.