Clinical trial NCT00676052: Dose-Ranging Study Of GSK233705B In Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Official title: Multicentre Dose Ranging Study for Once Daily GSK233705 in COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: COPD
Multicenter
GSK233705B
double-blind
Chronic Obstructive Pulmonary Disease (COPD)
randomized
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-05-12
Enrollment: 576
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29
timeFrame: Baseline (pre-dose Day 1) and Day 29
Secondary outcomes:
measure: Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29
timeFrame: Baseline (pre-dose Day 1) and Days 1 to 2, Days 28 to 29
measure: Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29
timeFrame: Baseline (pre-dose Day 1) and Days 1 to 2, Days 28 to 29
measure: Change From Baseline in Clinic Visit Trough FVC on Day 29
timeFrame: Baseline (pre-dose Day 1) and Day 29
Other outcomes:
Locations:
city: Jasper
country: United States
facility: GSK Investigational Site
state: Alabama
city: Glendale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Fountain Valley
country: United States
facility: GSK Investigational Site
state: California
city: Fullerton
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Riverside
country: United States
facility: GSK Investigational Site
state: California
city: Roseville
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Brandon
country: United States
facility: GSK Investigational Site
state: Florida
city: Panama City
country: United States
facility: GSK Investigational Site
state: Florida
city: South Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Coeur d'Alene
country: United States
facility: GSK Investigational Site
state: Idaho
city: Madisonville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Lafayette
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Sunset
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Saint Charles
country: United States
facility: GSK Investigational Site
state: Missouri
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Union
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Abingdon
country: United States
facility: GSK Investigational Site
state: Virginia
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: La Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Pergamino
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Tucuman
country: Argentina
facility: GSK Investigational Site
city: Dimitrovgrad
country: Bulgaria
facility: GSK Investigational Site
city: Ruse
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Bay Roberts
country: Canada
facility: GSK Investigational Site
state: Newfoundland and Labrador
city: Mississauga
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Saint Romuald
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sainte Jerome
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sainte-Foy
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Valparaiso
country: Chile
facility: GSK Investigational Site
state: Valparaíso
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Wiesloch
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Gelnhausen
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Luebeck
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Schmoelln
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Balassagyarmat
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Mátraháza
country: Hungary
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Almelo
country: Netherlands
facility: GSK Investigational Site
city: Eindhoven
country: Netherlands
facility: GSK Investigational Site
city: Hoofddorp
country: Netherlands
facility: GSK Investigational Site
city: Hoorn
country: Netherlands
facility: GSK Investigational Site
city: Cavite
country: Philippines
facility: GSK Investigational Site
city: Quezon City
country: Philippines
facility: GSK Investigational Site
city: Quezon City
country: Philippines
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Mueckelneck
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Parktown
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Bellville
country: South Africa
facility: GSK Investigational Site
city: Mowbray
country: South Africa
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Chiangmai
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
city: Songkla
country: Thailand
facility: GSK Investigational Site
city: Brighton
country: United Kingdom
facility: GSK Investigational Site
state: Sussex East
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Norwich
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.