Last updated: 11/04/2018 04:24:59
Safety Study Using GSK233705 And Tiotropium In Patients With Chronic Obstructive Pulmonary Disease
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Adverse events, blood pressure, heart rate, 12-lead electrocardiogram (ECG), Holter and Lead II ECG monitoring, ECG, lung function and clinical laboratory safety tests.
Timeframe: Up to Week 12
Secondary outcomes:
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.
Timeframe: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours Post-dose
Interventions:
Drug: GSK233705
Drug: Tiotropium
Drug: Placebo
Enrollment:
31
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
darotropium bromide
Collaborators
Not applicable
Study date(s)
December 2005 to June 2006
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
40 - 75 years
Accepts healthy volunteers
No
- Of non-childbearing potential.
- Diagnosed with COPD, as defined by the GOLD guidelines.
- 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.
Inclusion and exclusion criteria
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.
Trial location(s)
Location
GSK Investigational Site
Grosshansdorf, Schleswig-Holstein, Germany, 22927
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2006-13-06
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study AC2103473 can be found on the GSK Clinical Study Register.
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