NCT00279019

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Dec 2005

Shorter than P25 for phase_1

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 12, 2005

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

January 17, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 19, 2006

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 13, 2006

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 13, 2006

Completed
Last Updated

September 25, 2017

Status Verified

September 1, 2017

Enrollment Period

6 months

First QC Date

January 17, 2006

Last Update Submit

September 21, 2017

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

GSK233705Chronic Obstructive Pulmonary Disease (COPD)COPD

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • 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

Study Arms (16)

Subjects receiving treatment sequence 1

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 2

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 3

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 4

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 5

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 6

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 7

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 8

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 9

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 10

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 11

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 12

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 13

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 14

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 15

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Subjects receiving treatment sequence 16

EXPERIMENTAL

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

Drug: GSK233705Drug: TiotropiumDrug: Placebo

Interventions

GSK233705DRUG

GSK233705 will be given orally with dosing strengths of 10, 50, 100 and 250 micrograms/blister via the DISKUS inhaler.

Subjects receiving treatment sequence 1Subjects receiving treatment sequence 10Subjects receiving treatment sequence 11Subjects receiving treatment sequence 12Subjects receiving treatment sequence 13Subjects receiving treatment sequence 14Subjects receiving treatment sequence 15Subjects receiving treatment sequence 16Subjects receiving treatment sequence 2Subjects receiving treatment sequence 3Subjects receiving treatment sequence 4Subjects receiving treatment sequence 5Subjects receiving treatment sequence 6Subjects receiving treatment sequence 7Subjects receiving treatment sequence 8Subjects receiving treatment sequence 9
TiotropiumDRUG

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.

Subjects receiving treatment sequence 1Subjects receiving treatment sequence 10Subjects receiving treatment sequence 11Subjects receiving treatment sequence 12Subjects receiving treatment sequence 13Subjects receiving treatment sequence 14Subjects receiving treatment sequence 15Subjects receiving treatment sequence 16Subjects receiving treatment sequence 2Subjects receiving treatment sequence 3Subjects receiving treatment sequence 4Subjects receiving treatment sequence 5Subjects receiving treatment sequence 6Subjects receiving treatment sequence 7Subjects receiving treatment sequence 8Subjects receiving treatment sequence 9
PlaceboDRUG

Matching placebo will be given orally as overfoiled strips of 5 capsules, each containing lactose

Subjects receiving treatment sequence 1Subjects receiving treatment sequence 10Subjects receiving treatment sequence 11Subjects receiving treatment sequence 12Subjects receiving treatment sequence 13Subjects receiving treatment sequence 14Subjects receiving treatment sequence 15Subjects receiving treatment sequence 16Subjects receiving treatment sequence 2Subjects receiving treatment sequence 3Subjects receiving treatment sequence 4Subjects receiving treatment sequence 5Subjects receiving treatment sequence 6Subjects receiving treatment sequence 7Subjects receiving treatment sequence 8Subjects receiving treatment sequence 9

Eligibility Criteria

Age40 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

GSK Investigational Site

Berlin, 14050, Germany

Location

Related Links

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, ObstructiveLung DiseasesRespiratory Tract DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine DerivativesTropanesAzabicyclo CompoundsAza CompoundsOrganic ChemicalsAlkaloidsHeterocyclic CompoundsBridged Bicyclo Compounds, HeterocyclicHeterocyclic Compounds, Bridged-Ring

Study Officials

  • GSK Clinical Trials

    GlaxoSmithKline

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 17, 2006

First Posted

January 19, 2006

Study Start

December 12, 2005

Primary Completion

June 13, 2006

Study Completion

June 13, 2006

Last Updated

September 25, 2017

Record last verified: 2017-09

Data Sharing

IPD Sharing
Will share

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Available IPD Datasets

Informed Consent Form (AC2103473)Access
Individual Participant Data Set (AC2103473)Access
Annotated Case Report Form (AC2103473)Access
Dataset Specification (AC2103473)Access
Study Protocol (AC2103473)Access
Clinical Study Report (AC2103473)Access
Statistical Analysis Plan (AC2103473)Access

Locations

DE(3)