Clinical trial NCT00950807: GSK573719 Dose Ranging Study in Chronic Obstructive Pulmonary Disease
Official title: A Randomized, Double-Blind, Placebo-Controlled, 3-Way Cross-Over Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of GSK573719 Administered Once- and Twice-Daily in Subjects With COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Dose ranging
Chronic Bronchitis
Long-acting muscarinic antagonist
cross-over
COPD
Emphysema
Chronic Obstructive Pulmonary Disease (COPD)
anticholinergic
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-08-03
Enrollment: 176
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The study will evaluate the dose response, safety, and pharmacokinetics of GSK573719 compared with placebo in subjects with COPD.

Detailed description: This is multicenter, randomized, double-blind, double-dummy, placebo-controlled, three-way cross-over, incomplete block design study to evaluation of 5 doses of GSK573719 administered once-daily and 3 doses of GSK573719 administered twice-daily over 14 days in subjects with COPD and will include tiotropium as an open-label active control. The pharmacokinetic profile of GSK573719 will also be evaluated.

Eligibility criteria: Inclusion Criteria:

* A signed and dated written informed consent prior to study participation
* Males or females of non-childbearing potential
* 40 to 80 years of age
* COPD diagnosis
* 10 pack-years history or greater of cigarette smoking
* Post-bronchodilator FEV1/FVC ratio of 0.70 or less
* Post-bronchodilator FEV1 of 35 to 70% of predicted normal

Exclusion Criteria:

* Asthma
* Other significant respiratory disorders besides COPD, including alpha-1 deficiency
* Previous lung resection surgery
* Use of oral steroids or antibiotics for a COPD exacerbation within 6 weeks of screening
* Hospitalization for COPD or pneumonia within 3 months of screening
* Any significant disease that would put subject at risk through study participation
* BMI greater than 35
* Pacemaker
* Significantly abnormal ECG, Holter, or clinical lab finding (including Hepatitis B or C)
* Cancer
* Allergy or hypersensitivity to anticholinergics or inhaler excipients
* Diseases that would contra-indicate the use of anticholinergics
* Use of oral corticosteroids within 6 weeks of screening
* Use of long-acting beta-agonists within 48 hours of screening
* Use of tiotropium within 14 days of screening
* Use of theophyllines or anti-leukotrienes within 48 hours of screening
* Use of short-acting bronchodilators within 4 to 6 hours of screening
* Use of investigational medicines within 30 days of screening
* Use of high dose inhaled corticosteroids
* Use of long-term oxygen therapy, CPAP or NIPPV
* Previous use of GSK573719

Primary outcomes:
measure: Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period
timeFrame: Baseline and Day 15 of each treatment period (up to Study Day 71)
Secondary outcomes:
measure: Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period
timeFrame: Baseline and Day 14 of each treatment period (TP; up to Study Day 70)
measure: Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period
timeFrame: Baseline and Day (D) 14 of each treatment period (TP; up to Study Day 70)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Upland
country: United States
facility: GSK Investigational Site
state: California
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Easley
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Gaffney
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Seneca
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: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Wiesbaden
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Grosshansdorf
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Donohue JF, Anzueto A, Brooks J, Mehta R, Kalberg C, Crater G. A randomized, double-blind dose-ranging study of the novel LAMA GSK573719 in patients with COPD. Respir Med. 2012 Jul;106(7):970-9. doi: 10.1016/j.rmed.2012.03.012. Epub 2012 Apr 10.