Dose-Ranging Study Of GSK233705B In Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Multicentre Dose Ranging Study for Once Daily GSK233705 in COPD

The purpose of this study is to evaluate the efficacy and safety of GSK233705B compared with placebo in subjects with COPD.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: GSK233705 12.5mcg; Drug: GSK233705 25mcg; Drug: GSK233705 50mcg; Drug: GSK233705 100mcg; Drug: GSK233705 200mcg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 576
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Tucuman, Argentina, 4000
    • GSK Investigational Site
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, CP1900
      • GSK Investigational Site
    • Mar del Plata, Buenos Aires, Argentina, B7600FZN
      • GSK Investigational Site
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • GSK Investigational Site
    • Pergamino, Buenos Aires, Argentina, 2700
      • GSK Investigational Site
• Bulgaria
  • Dimitrovgrad, Bulgaria, 6400
    • GSK Investigational Site
  • Ruse, Bulgaria, 7000
    • GSK Investigational Site
  • Sofia, Bulgaria, 1431
    • GSK Investigational Site
  • Sofia, Bulgaria
    • GSK Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • GSK Investigational Site
  • Newfoundland and Labrador
    • Bay Roberts, Newfoundland and Labrador, Canada, A0A 1G0
      • GSK Investigational Site
  • Ontario
    • Mississauga, Ontario, Canada, L5A 3V4
      • GSK Investigational Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 1N8
      • GSK Investigational Site
  • Quebec
    • Saint Romuald, Quebec, Canada, G6W 5M6
      • GSK Investigational Site
    • Sainte Jerome, Quebec, Canada, J7Z 5T3
      • GSK Investigational Site
    • Sainte-Foy, Quebec, Canada, G1V 4G5
      • GSK Investigational Site
• Chile
  • Santiago, Chile, 8380453
    • GSK Investigational Site
  • Región Metro De Santiago
    • Santiago, Región Metro De Santiago, Chile, 7500551
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7500691
      • GSK Investigational Site
  • Valparaíso
    • Valparaiso, Valparaíso, Chile, 2341131
      • GSK Investigational Site
• Germany
  • Berlin, Germany, 14057
    • GSK Investigational Site
  • Berlin, Germany, 10117
    • GSK Investigational Site
  • Berlin, Germany, 10717
    • GSK Investigational Site
  • Berlin, Germany, 10787
    • GSK Investigational Site
  • Berlin, Germany, 10559
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Wiesloch, Baden-Wuerttemberg, Germany, 69168
      • GSK Investigational Site
  • Hessen
    • Gelnhausen, Hessen, Germany, 63571
      • GSK Investigational Site
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • GSK Investigational Site
    • Hannover, Niedersachsen, Germany, 30167
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • GSK Investigational Site
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39112
      • GSK Investigational Site
  • Schleswig-Holstein
    • Luebeck, Schleswig-Holstein, Germany, 23552
      • GSK Investigational Site
  • Thueringen
    • Schmoelln, Thueringen, Germany, 04626
      • GSK Investigational Site
• Hungary
  • Balassagyarmat, Hungary, 2660
    • GSK Investigational Site
  • Budapest, Hungary, 1095
    • GSK Investigational Site
  • Budapest, Hungary, H-1529
    • GSK Investigational Site
  • Mátraháza, Hungary, 3233
    • GSK Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 152-703
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 133--792
    • GSK Investigational Site
• Netherlands
  • Almelo, Netherlands, 7609 PP
    • GSK Investigational Site
  • Eindhoven, Netherlands, 5623 EJ
    • GSK Investigational Site
  • Hoofddorp, Netherlands, 2134 TM
    • GSK Investigational Site
  • Hoorn, Netherlands, 1624 NP
    • GSK Investigational Site
• Philippines
  • Cavite, Philippines, 4114
    • GSK Investigational Site
  • Quezon City, Philippines, 1100
    • GSK Investigational Site
  • Quezon City, Philippines, 1109
    • GSK Investigational Site
• Romania
  • Brasov, Romania, 500112
    • GSK Investigational Site
  • Bucharest, Romania, 020125
    • GSK Investigational Site
  • Iasi, Romania, 700115
    • GSK Investigational Site
• South Africa
  • Bellville, South Africa, 7531
    • GSK Investigational Site
  • Mowbray, South Africa, 7700
    • GSK Investigational Site
  • Gauteng
    • Cape Town, Gauteng, South Africa, 7505
      • GSK Investigational Site
    • Mueckelneck, Gauteng, South Africa, 0001
      • GSK Investigational Site
    • Parktown, Gauteng, South Africa, 2193
      • GSK Investigational Site
• Thailand
  • Bangkok, Thailand, 10700
    • GSK Investigational Site
  • Chiangmai, Thailand, 50200
    • GSK Investigational Site
  • Khon Kaen, Thailand, 40002
    • GSK Investigational Site
  • Songkla, Thailand, 90110
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, SE5 9PJ
    • GSK Investigational Site
  • Norwich, United Kingdom, NR4 7UY
    • GSK Investigational Site
  • Sussex East
    • Brighton, Sussex East, United Kingdom, BN2 5BE
      • GSK Investigational Site
• United States
  • Alabama
    • Jasper, Alabama, United States, 35501
      • GSK Investigational Site
  • Arizona
    • Glendale, Arizona, United States, 85306
      • GSK Investigational Site
  • California
    • Fountain Valley, California, United States, 92708
      • GSK Investigational Site
    • Fullerton, California, United States, 92835
      • GSK Investigational Site
    • Los Angeles, California, United States, 90095
      • GSK Investigational Site
    • Los Angeles, California, United States, 90048
      • GSK Investigational Site
    • Riverside, California, United States, 92506
      • GSK Investigational Site
    • Roseville, California, United States, 95661
      • GSK Investigational Site
    • San Diego, California, United States, 92103-8415
      • GSK Investigational Site
  • Florida
    • Brandon, Florida, United States, 33511
      • GSK Investigational Site
    • Panama City, Florida, United States, 32405
      • GSK Investigational Site
    • South Miami, Florida, United States, 33143
      • GSK Investigational Site
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • GSK Investigational Site
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • GSK Investigational Site
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • GSK Investigational Site
    • Sunset, Louisiana, United States, 70584
      • GSK Investigational Site
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • GSK Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406-7108
      • GSK Investigational Site
    • Greenville, South Carolina, United States, 29615
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
    • Union, South Carolina, United States, 29379
      • GSK Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • GSK Investigational Site
  • Virginia
    • Abingdon, Virginia, United States, 24210
      • GSK Investigational Site
    • Richmond, Virginia, United States, 23229
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A signed and dated written informed consent prior to study participation.
• Male or female adults.

A female is eligible to enter and participate in this study if she is of:

non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post-menopausal; or child-bearing potential, has a negative pregnancy test at Visit 1/Visit 1A, and agrees to one of the protocol-specified acceptable contraceptive methods used consistently and correctly (i.e. according to the approved product label and the instructions of the physician for the duration of the study - Screening through follow-up contact)

• 40 to 80 years of age at Visit 1
• An established clinical history of COPD
• Current or previous cigarette smokers with a history of cigarette smoking of ≥ 10 pack-years 1.
• A post-albuterol/salbutamol FEV1/FVC ratio of ≤0.70 and a post-albuterol/salbutamol FEV1 of ≥35 and ≤70% of predicted normal values

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

• Women who are pregnant or lactating.
• A current diagnosis of asthma.
• Known respiratory disorders other than COPD including but not limited to α-1 antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease.
• Any previous lung resection surgery (e.g., lung volume reduction surgery or lobectomy)
• Clinically significant Chest X-ray or computed tomography (CT) scan abnormalities within 6 months prior to Visit 1 that are not believed to be due to COPD.
• Use of oral corticosteroids or antibiotics for COPD within 6 weeks prior to Visit 1.
• Hospitalization for COPD or pneumonia within 3 months prior to Visit 1.
• Use of antibiotics for a lower respiratory tract infection within 30 days prior to Visit 1.
• Clinically significant and uncontrolled cardiovascular, neurological, psychiatric, renal, gastro-intestinal, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities.
• An abnormal and clinically significant 12-lead electrocardiogram (ECG) that results in active medical problem.
• Positive for Hepatitis B or Hepatitis C at Visit 1.
• A current malignancy or previous history of cancer in remission for <5 years prior to Visit 1
• A history of allergy or hypersensitivity to ipratropium, tiotropium, or atropine and any of their derivatives, lactose/milk protein or magnesium stearate.
• Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator would prevent use of an inhaled anticholingeric.
• Medically unable to withhold albuterol/salbutamol for 6 hours prior to spirometry testing at each study visit or to withhold ipratropium (if applicable) for the 6-hour period prior to the first 3 study visits (ipratropium cannot be used after Visit 3).
• Additional Medications: Unable to stop using certain medications such as bronchodilators and corticosteroids for the protocol-specified times prior to Visit 1 (the Investigator will discuss the specific medications)
• Use of inhaled corticosteroids at a dose greater than 1000 mcg/day of fluticasone propionate or equivalent within 30 days prior to Visit 1.
• Use of long-term oxygen therapy (LTOT) or supplemental oxygen required for greater than 12 hours a day. Oxygen use as needed is not exclusionary.
• Clinically significant sleep apnea that requires continuous positive airway pressure (CPAP)
• Use of regular nebulized therapy
• Use of nocturnal positive pressure or non-invasive positive pressure ventilation (NIPPV)
• Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1.
• An investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the above who is involved in this study
• History of psychiatric disease, intellectual deficiency, poor motivation, substance abuse in the two years prior to Visit 1 (including drug and alcohol), or other conditions, which will limit the validity of informed consent to participate in the study.
• Use of GSK233705B in previous studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; GSK233705 12.5mcg	Drug: GSK233705 12.5mcg; Once daily via dry powder inhaler
Experimental: Arm 2; GSK233705 25mcg	Drug: GSK233705 25mcg; once daily via dry powder inhaler
Experimental: Arm 3; GSK233705 50mcg	Drug: GSK233705 50mcg; Once daily via dry powder inhaler
Experimental: Arm 4; GSK233705 100mcg	Drug: GSK233705 100mcg; Once daily via dry powder inhaler
Experimental: Arm 5; GSK233705 200mcg	Drug: GSK233705 200mcg; Once daily via dry powder inhaler
Placebo Comparator: Arm 6; Placebo	Drug: Placebo; Once daily via dry powder imhaler

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29	The trough FEV1 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28. The Baseline FEV1 is the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose [time 0] on Day 1. Change from Baseline was calculated by subtracting the post-baseline assessment value from the Baseline value.	Baseline (pre-dose Day 1) and Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29	Weighted means serial FEV1 was derived by calculating the area under curve (AUC), and then dividing by the time interval over which the AUC was calculated. Baseline was defined at pre-dose Day 1. The weighted mean change from Baseline is the weighted mean minus Baseline. The AUC was calculated using the trapezoidal rule. For all post-dose observations, actual times that the spirometry measurements were conducted was used for the calculation. Pre-dose observations were counted as 0 hr observations - that is they had their time set to the time of dosing. The pre-dose value used for the calculation of the AUC was the mean of the two pre-dose observations (-30 and 0 min for Day 1 or 28). If one of these observations was missing, the remaining single pre-dose observation was used.	Baseline (pre-dose Day 1) and Days 1 to 2, Days 28 to 29
Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29	Weighted means serial FVC was derived by calculating the AUC, and then dividing by the time interval over which the AUC was calculated. Baseline was defined at pre-dose Day 1. The weighted mean change from Baseline is the weighted mean minus Baseline. The AUC was calculated using the trapezoidal rule. For all post-dose observations, actual times that the spirometry measurements were conducted was used for the calculation. Pre-dose observations were counted as 0 hr observations - that is they had their time set to the time of dosing. The pre-dose value used for the calculation of the AUC was the mean of the two pre-dose observations (-30 and 0 min for Day 1 or 28). If one of these observations was missing, the remaining single pre-dose observation was used.	Baseline (pre-dose Day 1) and Days 1 to 2, Days 28 to 29
Change From Baseline in Clinic Visit Trough FVC on Day 29	The trough FVC is defined as the mean of the FVC values obtained 23 and 24 hours after dosing on Day 28. The Baseline FVC is the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose [time 0] on Day 1. Change from Baseline was calculated by subtracting the post-baseline assessment value from the Baseline value.	Baseline (pre-dose Day 1) and Day 29

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Bateman E, Feldman G, Kilbride S, Brooks J, Mehta R, Harris S, Maden C, Crater G. Efficacy and safety of the long-acting muscarinic antagonist GSK233705 delivered once daily in patients with COPD. Clin Respir J. 2012 Oct;6(4):248-57. doi: 10.1111/j.1752-699X.2011.00278.x. Epub 2012 Feb 13.

Helpful 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2008
• Primary Completion (Actual): December 22, 2008
• Study Completion (Actual): December 22, 2008

Study Registration Dates

• First Submitted: May 8, 2008
• First Submitted That Met QC Criteria: May 8, 2008
• First Posted (Estimate): May 12, 2008

Study Record Updates

• Last Update Posted (Actual): October 9, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: COPD; randomized; double-blind; Multicenter; Chronic Obstructive Pulmonary Disease (COPD); GSK233705B
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: AC2110664

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.

Study Data/Documents

1. Annotated Case Report Form
   Information identifier: AC2110664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: AC2110664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: AC2110664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: AC2110664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: AC2110664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: AC2110664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: AC2110664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register