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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00279019
First Posted: January 19, 2006
Last Update Posted: September 22, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose

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.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive Drug: GSK233705 Drug: Tiotropium Drug: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Adverse events, blood pressure, heart rate, 12-lead electrocardiogram (ECG), Holter and Lead II ECG monitoring, ECG, lung function and clinical laboratory safety tests. [ Time Frame: Up to Week 12 ]

Secondary Outcome Measures:
  • 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. [ Time Frame: Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours Post-dose ]

Enrollment: 31
Actual Study Start Date: December 12, 2005
Study Completion Date: June 13, 2006
Primary Completion Date: June 13, 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Subjects receiving treatment sequence 1
Eligible subjects will receive treatment sequence 1; GSK233705 20 micrograms, GSK233705 100 micrograms, tiotropium and placebo.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 2
Eligible subjects will receive treatment sequence 2; GSK233705 20 micrograms, Placebo, GSK233705 50 micrograms and tiotropium.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 3
Eligible subjects will receive treatment sequence 3; GSK233705 20 micrograms, tiotropium, Placebo and GSK233705 50 micrograms.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 4
Eligible subjects will receive treatment sequence 4; GSK233705 20 micrograms, placebo, tiotropium and GSK233705 50 micrograms.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 5
Eligible subjects will receive treatment sequence 5; Placebo, tiotropium, GSK233705 20 micrograms and GSK233705 50 micrograms.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 6
Eligible subjects will receive treatment sequence 6; Placebo, GSK233705 20 micrograms, GSK233705 50 micrograms and tiotropium.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 7
Eligible subjects will receive treatment sequence 7; tiotropium, GSK233705 20 micrograms, GSK233705 50 micrograms and Placebo.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 8
Eligible subjects will receive treatment sequence 8; tiotropium, GSK233705 20 micrograms, Placebo and GSK233705 50 micrograms.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 9
Eligible subjects will receive treatment sequence 9; GSK233705 20 micrograms, tiotropium, GSK233705 50 micrograms and Placebo.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 10
Eligible subjects will receive treatment sequence 10; GSK233705 20 micrograms, GSK233705 100 micrograms, Placebo and tiotropium.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 11
Eligible subjects will receive treatment sequence 11; Placebo, GSK233705 20 micrograms, tiotropium, and GSK233705 50 micrograms.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 12
Eligible subjects will receive treatment sequence 12; Tiotropium, Placebo, GSK233705 20 micrograms and GSK233705 50 micrograms.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 13
Eligible subjects will receive treatment sequence 13; Placebo, GSK233705 20 micrograms, GSK233705 50 micrograms and GSK233705 100 micrograms.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 14
Eligible subjects will receive treatment sequence 14; GSK233705 20 micrograms, placebo, GSK233705 50 micrograms and GSK233705 100 micrograms.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 15
Eligible subjects will receive treatment sequence 15; GSK233705 20 micrograms, GSK233705 100 micrograms, Placebo and GSK233705 50 micrograms.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Experimental: Subjects receiving treatment sequence 16
Eligible subjects will receive treatment sequence 16; GSK233705 20 micrograms, GSK233705 100 micrograms, GSK233705 50 micrograms and Placebo.
Drug: GSK233705
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Drug: 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.
Drug: Placebo
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00279019


Locations
Germany
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
GSK Investigational Site
Grosshansdorf, Schleswig-Holstein, Germany, 22927
GSK Investigational Site
Berlin, Germany, 14050
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: AC2103473
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: AC2103473
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: AC2103473
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: AC2103473
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: AC2103473
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: AC2103473
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: AC2103473
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00279019     History of Changes
Other Study ID Numbers: AC2103473
First Submitted: January 17, 2006
First Posted: January 19, 2006
Last Update Posted: September 22, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
URL: http://

Keywords provided by GlaxoSmithKline:
GSK233705
Chronic Obstructive Pulmonary Disease (COPD)
COPD

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Chronic Disease
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Tiotropium Bromide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action