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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT01319019

Collaborator

(none)

437

Enrollment

Locations

Arms

Duration (Months)

8.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: GSK961081 Drug: Salmeterol Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

437 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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 Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK961081 100 mcg QD	Drug: GSK961081 Comparison of different doses and dosing regimens of the drug
Experimental: GSK961081 100mcg BD	Drug: GSK961081 Comparison of different doses and dosing regimens of the drug
Experimental: GSK961081 200mcg QD	Drug: GSK961081 Comparison of different doses and dosing regimens of the drug
Experimental: GSK961081 400mcg QD	Drug: GSK961081 Comparison of different doses and dosing regimens of the drug
Experimental: GSK961081 400mcg BD	Drug: GSK961081 Comparison of different doses and dosing regimens of the drug
Experimental: GSK961081 800mcg QD	Drug: GSK961081 Comparison of different doses and dosing regimens of the drug
Active Comparator: Salmeterol 50mcg BD	Drug: Salmeterol Positive control
Placebo Comparator: Placebo	Drug: Placebo Placebo arm

Outcome Measures

Primary Outcome Measures

Change in FEV1 from baseline in pre-dose AM trough. [28 Day]
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)

Secondary Outcome Measures

Weighted Mean and Serial FEV1 at multiple timepoints [28 Days]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Tallinn		Estonia	10138
2	GSK Investigational Site	Tallinn		Estonia	13419
3	GSK Investigational Site	Tallinn		Estonia	13619
4	GSK Investigational Site	Tartu		Estonia	51014
5	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
6	GSK Investigational Site	Gelnhausen	Hessen	Germany	63571
7	GSK Investigational Site	Dresden	Sachsen	Germany	01307
8	GSK Investigational Site	Luebeck	Schleswig-Holstein	Germany	23552
9	GSK Investigational Site	Berlin		Germany	10367
10	GSK Investigational Site	Berlin		Germany	10717
11	GSK Investigational Site	Berlin		Germany	10787
12	GSK Investigational Site	Almelo		Netherlands	7609 PP
13	GSK Investigational Site	Breda		Netherlands	4819 EV
14	GSK Investigational Site	Eindhoven		Netherlands	5623 EJ
15	GSK Investigational Site	Hoorn		Netherlands	1624 NP
16	GSK Investigational Site	Veldhoven		Netherlands	5504 DB
17	GSK Investigational Site	Zutphen		Netherlands	7207 AE
18	GSK Investigational Site	Bucharest		Romania	020125
19	GSK Investigational Site	Bucharest		Romania	050159
20	GSK Investigational Site	Iasi		Romania	700115
21	GSK Investigational Site	Timisoara		Romania	300310
22	GSK Investigational Site	Ekaterinburg		Russian Federation	620109
23	GSK Investigational Site	Moscow		Russian Federation	105 077
24	GSK Investigational Site	Moscow		Russian Federation	115446
25	GSK Investigational Site	St. Petersburg		Russian Federation	197022
26	GSK Investigational Site	Tomsk		Russian Federation	634001
27	GSK Investigational Site	Bratislava		Slovakia	826 06
28	GSK Investigational Site	Kosice		Slovakia	040 01
29	GSK Investigational Site	Nitra		Slovakia	949 01
30	GSK Investigational Site	Nove Zamky		Slovakia	940 01
31	GSK Investigational Site	Zvolen		Slovakia	960 01
32	GSK Investigational Site	Bellville		South Africa	7530
33	GSK Investigational Site	Durban		South Africa	4001
34	GSK Investigational Site	Gatesville		South Africa	7764
35	GSK Investigational Site	Mowbray		South Africa	7700
36	GSK Investigational Site	Panorama		South Africa	7500
37	GSK Investigational Site	Tygerberg		South Africa	7505
38	GSK Investigational Site	Boden		Sweden	SE-961 64
39	GSK Investigational Site	Göteborg		Sweden	SE-413 45
40	GSK Investigational Site	Lund		Sweden	SE-221 85
41	GSK Investigational Site	Stockholm		Sweden	SE-171 76
42	GSK Investigational Site	Dnipropetrovsk		Ukraine	49074
43	GSK Investigational Site	Ivano-Frankivsk		Ukraine	76018
44	GSK Investigational Site	Kharkiv		Ukraine	61124
45	GSK Investigational Site	Kiev		Ukraine	03680
46	GSK Investigational Site	Kyiv		Ukraine	03115
47	GSK Investigational Site	Kyiv		Ukraine	03680
48	GSK Investigational Site	Simferopol		Ukraine	95043
49	GSK Investigational Site	Vinnytsia		Ukraine	21029