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

Primary Purpose

Pulmonary Disease, Chronic Obstructive

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
GSK233705
Tiotropium
Placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive focused on measuring GSK233705, Chronic Obstructive Pulmonary Disease (COPD), COPD

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Subjects receiving treatment sequence 1

Subjects receiving treatment sequence 2

Subjects receiving treatment sequence 3

Subjects receiving treatment sequence 4

Subjects receiving treatment sequence 5

Subjects receiving treatment sequence 6

Subjects receiving treatment sequence 7

Subjects receiving treatment sequence 8

Subjects receiving treatment sequence 9

Subjects receiving treatment sequence 10

Subjects receiving treatment sequence 11

Subjects receiving treatment sequence 12

Subjects receiving treatment sequence 13

Subjects receiving treatment sequence 14

Subjects receiving treatment sequence 15

Subjects receiving treatment sequence 16

Arm Description

Eligible subjects will receive treatment sequence 1; GSK233705 20 micrograms, GSK233705 100 micrograms, tiotropium and placebo.

Eligible subjects will receive treatment sequence 2; GSK233705 20 micrograms, Placebo, GSK233705 50 micrograms and tiotropium.

Eligible subjects will receive treatment sequence 3; GSK233705 20 micrograms, tiotropium, Placebo and GSK233705 50 micrograms.

Eligible subjects will receive treatment sequence 4; GSK233705 20 micrograms, placebo, tiotropium and GSK233705 50 micrograms.

Eligible subjects will receive treatment sequence 5; Placebo, tiotropium, GSK233705 20 micrograms and GSK233705 50 micrograms.

Eligible subjects will receive treatment sequence 6; Placebo, GSK233705 20 micrograms, GSK233705 50 micrograms and tiotropium.

Eligible subjects will receive treatment sequence 7; tiotropium, GSK233705 20 micrograms, GSK233705 50 micrograms and Placebo.

Eligible subjects will receive treatment sequence 8; tiotropium, GSK233705 20 micrograms, Placebo and GSK233705 50 micrograms.

Eligible subjects will receive treatment sequence 9; GSK233705 20 micrograms, tiotropium, GSK233705 50 micrograms and Placebo.

Eligible subjects will receive treatment sequence 10; GSK233705 20 micrograms, GSK233705 100 micrograms, Placebo and tiotropium.

Eligible subjects will receive treatment sequence 11; Placebo, GSK233705 20 micrograms, tiotropium, and GSK233705 50 micrograms.

Eligible subjects will receive treatment sequence 12; Tiotropium, Placebo, GSK233705 20 micrograms and GSK233705 50 micrograms.

Eligible subjects will receive treatment sequence 13; Placebo, GSK233705 20 micrograms, GSK233705 50 micrograms and GSK233705 100 micrograms.

Eligible subjects will receive treatment sequence 14; GSK233705 20 micrograms, placebo, GSK233705 50 micrograms and GSK233705 100 micrograms.

Eligible subjects will receive treatment sequence 15; GSK233705 20 micrograms, GSK233705 100 micrograms, Placebo and GSK233705 50 micrograms.

Eligible subjects will receive treatment sequence 16; GSK233705 20 micrograms, GSK233705 100 micrograms, GSK233705 50 micrograms and Placebo.

Outcomes

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.

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.

Full Information

First Posted
January 17, 2006
Last Updated
September 21, 2017
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00279019
Brief Title
Safety Study Using GSK233705 And Tiotropium In Patients With Chronic Obstructive Pulmonary Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
December 12, 2005 (Actual)
Primary Completion Date
June 13, 2006 (Actual)
Study Completion Date
June 13, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
Keywords
GSK233705, Chronic Obstructive Pulmonary Disease (COPD), COPD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Subjects receiving treatment sequence 1
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 1; GSK233705 20 micrograms, GSK233705 100 micrograms, tiotropium and placebo.
Arm Title
Subjects receiving treatment sequence 2
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 2; GSK233705 20 micrograms, Placebo, GSK233705 50 micrograms and tiotropium.
Arm Title
Subjects receiving treatment sequence 3
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 3; GSK233705 20 micrograms, tiotropium, Placebo and GSK233705 50 micrograms.
Arm Title
Subjects receiving treatment sequence 4
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 4; GSK233705 20 micrograms, placebo, tiotropium and GSK233705 50 micrograms.
Arm Title
Subjects receiving treatment sequence 5
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 5; Placebo, tiotropium, GSK233705 20 micrograms and GSK233705 50 micrograms.
Arm Title
Subjects receiving treatment sequence 6
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 6; Placebo, GSK233705 20 micrograms, GSK233705 50 micrograms and tiotropium.
Arm Title
Subjects receiving treatment sequence 7
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 7; tiotropium, GSK233705 20 micrograms, GSK233705 50 micrograms and Placebo.
Arm Title
Subjects receiving treatment sequence 8
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 8; tiotropium, GSK233705 20 micrograms, Placebo and GSK233705 50 micrograms.
Arm Title
Subjects receiving treatment sequence 9
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 9; GSK233705 20 micrograms, tiotropium, GSK233705 50 micrograms and Placebo.
Arm Title
Subjects receiving treatment sequence 10
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 10; GSK233705 20 micrograms, GSK233705 100 micrograms, Placebo and tiotropium.
Arm Title
Subjects receiving treatment sequence 11
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 11; Placebo, GSK233705 20 micrograms, tiotropium, and GSK233705 50 micrograms.
Arm Title
Subjects receiving treatment sequence 12
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 12; Tiotropium, Placebo, GSK233705 20 micrograms and GSK233705 50 micrograms.
Arm Title
Subjects receiving treatment sequence 13
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 13; Placebo, GSK233705 20 micrograms, GSK233705 50 micrograms and GSK233705 100 micrograms.
Arm Title
Subjects receiving treatment sequence 14
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 14; GSK233705 20 micrograms, placebo, GSK233705 50 micrograms and GSK233705 100 micrograms.
Arm Title
Subjects receiving treatment sequence 15
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 15; GSK233705 20 micrograms, GSK233705 100 micrograms, Placebo and GSK233705 50 micrograms.
Arm Title
Subjects receiving treatment sequence 16
Arm Type
Experimental
Arm Description
Eligible subjects will receive treatment sequence 16; GSK233705 20 micrograms, GSK233705 100 micrograms, GSK233705 50 micrograms and Placebo.
Intervention Type
Drug
Intervention Name(s)
GSK233705
Intervention Description
GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.
Intervention Type
Drug
Intervention Name(s)
Tiotropium
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
GSK Investigational Site
City
Grosshansdorf
State/Province
Schleswig-Holstein
ZIP/Postal Code
22927
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
14050
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AC2103473
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AC2103473
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AC2103473
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AC2103473
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AC2103473
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AC2103473
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AC2103473
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register

Learn more about this trial

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

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