Clinical trial NCT01319019: A 4-week Dose-Ranging, Dose-Interval, Efficacy, Safety and Tolerability Study of GSK961081 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Official title: A 4-week Dose-Ranging, Dose-Interval, Efficacy, Safety and Tolerability Study of GSK961081 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: lung function
bronchodilator
COPD, dose response, dosing interval, efficacy, safety, PD, PK
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-03-21
Enrollment: 437
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is primarily designed to assess the dose response, dose interval, efficacy and safety of three once daily (QD) doses (100mcg, 400mcg and 800mcg) and three twice daily (BID) doses (100mcg, 200mcg and 400mcg,) of GSK961081 administered via DISKUS™ for 28 days in subjects with moderate/severe COPD versus placebo. Salmeterol 50mcg BID is included in the study as an active comparator.

Detailed description: This is a phase IIb multicentre, randomised, double-blind, double-dummy, placebo- and active-controlled, parallel-group, dose-ranging and dose-interval study. Eligible subjects will enter a seven-day run-in period followed by 28 days of double-blind, double-dummy treatment via the DISKUS inhaler. The study will consist of 8 visits, mainly conducted on an outpatient basis, 6 of which will be clinic visits and 2 of which will be phone contacts, including a post-treatment visit to follow up any adverse events. There will be approximately 425 subjects randomised to the study.

Eligibility criteria: Inclusion Criteria:

* Outpatient Subjects
* Subjects who give their signed and dated informed consent to participate
* 40 or more years of age, inclusive, at Visit 1
* Male or females
* Subjects with an established clinical history of COPD
* Current or previous cigarette smokers with a history of ≥ 10 pack-years of cigarette smoking
* Subjects with the following liver function test values:
* Subjects with a measured post-salbutamol FEV1/FVC ratio of \< 0.70 at Visit 1 (Screening).
* Subjects with a measured post-salbutamol FEV1 30-70% of predicted normal values

Exclusion Criteria:

* Women who are pregnant or lactating or are planning to become pregnant during the study.
* Current diagnosis of asthma
* Other significant respiratory disorders besides COPD, including alpha-1 deficiency
* Previous lung resection surgery
* Significant abnormalities in chest x-ray presentation
* Hospitalization for a COPD exacerbation within 12 weeks prior screening
* Use of oral corticosteroids or antibiotics for COPD or antibiotics for a lower respiratory tract infection within 6 weeks
* Any significant disease that would put subject at risk through study participation
* BMI greater than 35
* Pacemaker
* Significantly abnormal ECG, clinical lab finding (including Hepatitis B or C)
* Cancer
* Allergy or hypersensitivity to beta adrenergic receptor-agonist, sympathomimetic, anticholinergic/anti-muscarinic receptor antagonist, or inhaler excipients
* Diseases that would contra-indicate the use of anticholinergics
* Use of sysemic corticosteroids within 6 weeks of screening
* Use of long-acting beta-agonists within 48 hours of screening
* Use of tiotropium within 7 days of screening
* Use of theophyllines or anti-leukotrienes within 48 hours of screening
* Use of short-acting bronchodilators within 4 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
* Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1
* Regular (q.i.d or greater) use of short acting bronchodilators, including nebulized therapy
* Affiliation with Investigator Site
* Questionable Validity of Consent
* Previous use of GSK961081

Primary outcomes:
measure: Change in FEV1 from baseline in pre-dose AM trough.
timeFrame: 28 Day
Secondary outcomes:
measure: Weighted Mean and Serial FEV1 at multiple timepoints
timeFrame: 28 Days
Other outcomes:
Locations:
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Gelnhausen
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Luebeck
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: Berlin
country: Germany
facility: GSK Investigational Site
city: Almelo
country: Netherlands
facility: GSK Investigational Site
city: Breda
country: Netherlands
facility: GSK Investigational Site
city: Eindhoven
country: Netherlands
facility: GSK Investigational Site
city: Hoorn
country: Netherlands
facility: GSK Investigational Site
city: Veldhoven
country: Netherlands
facility: GSK Investigational Site
city: Zutphen
country: Netherlands
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Kosice
country: Slovakia
facility: GSK Investigational Site
city: Nitra
country: Slovakia
facility: GSK Investigational Site
city: Nove Zamky
country: Slovakia
facility: GSK Investigational Site
city: Zvolen
country: Slovakia
facility: GSK Investigational Site
city: Bellville
country: South Africa
facility: GSK Investigational Site
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Gatesville
country: South Africa
facility: GSK Investigational Site
city: Mowbray
country: South Africa
facility: GSK Investigational Site
city: Panorama
country: South Africa
facility: GSK Investigational Site
city: Tygerberg
country: South Africa
facility: GSK Investigational Site
city: Boden
country: Sweden
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Lund
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Ivano-Frankivsk
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kiev
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Simferopol
country: Ukraine
facility: GSK Investigational Site
city: Vinnytsia
country: Ukraine
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wielders PL, Ludwig-Sengpiel A, Locantore N, Baggen S, Chan R, Riley JH. A new class of bronchodilator improves lung function in COPD: a trial with GSK961081. Eur Respir J. 2013 Oct;42(4):972-81. doi: 10.1183/09031936.00165712. Epub 2013 Feb 21.