A 4-week Dose-Ranging, Dose-Interval, Efficacy, Safety and Tolerability Study of GSK961081 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A 4-week Dose-Ranging, Dose-Interval, Efficacy, Safety and Tolerability Study of GSK961081 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01319019
• Other study ID #: 115032
• Status: Completed
• Phase: Phase 2
• First received: March 3, 2011
• Last updated: November 30, 2016
• Start date: December 2010
• Est. completion date: September 2011

Study information

• Verified date: November 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 437
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• GSK961081
Comparison of different doses and dosing regimens of the drug
• Salmeterol
Positive control
• Placebo
Placebo arm

Locations

Country	Name	City	State
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Gelnhausen	Hessen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Netherlands	GSK Investigational Site	Almelo
Netherlands	GSK Investigational Site	Breda
Netherlands	GSK Investigational Site	Eindhoven
Netherlands	GSK Investigational Site	Hoorn
Netherlands	GSK Investigational Site	Veldhoven
Netherlands	GSK Investigational Site	Zutphen
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Tomsk
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Kosice
Slovakia	GSK Investigational Site	Nitra
Slovakia	GSK Investigational Site	Nove Zamky
Slovakia	GSK Investigational Site	Zvolen
South Africa	GSK Investigational Site	Bellville
South Africa	GSK Investigational Site	Durban
South Africa	GSK Investigational Site	Gatesville
South Africa	GSK Investigational Site	Mowbray
South Africa	GSK Investigational Site	Panorama
South Africa	GSK Investigational Site	Tygerberg
Sweden	GSK Investigational Site	Boden
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Lund
Sweden	GSK Investigational Site	Stockholm
Ukraine	GSK Investigational Site	Dnipropetrovsk
Ukraine	GSK Investigational Site	Ivano-Frankivsk
Ukraine	GSK Investigational Site	Kharkiv
Ukraine	GSK Investigational Site	Kiev
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Simferopol
Ukraine	GSK Investigational Site	Vinnytsia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Estonia,  Germany,  Netherlands,  Romania,  Russian Federation,  Slovakia,  South Africa,  Sweden,  Ukraine, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in FEV1 from baseline in pre-dose AM trough.	Pre-dose change in AM FEV1 on day 29 vs baseline . (defined as the mean values recorded 11 and 12 hours after the PM dose on day 28)	28 Day
Secondary	Weighted Mean and Serial FEV1 at multiple timepoints	In the subset of patients with overnight spirometry on day 28 (pre-dose and post dose after 15,30, and 60 min and 2, 4,6, 11 and 12 hours)	28 Days

External Links

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