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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: GSK961081; Drug: Salmeterol

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 Type: Interventional
• Enrollment (Actual): 437
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia, 13419
    • GSK Investigational Site
  • Tallinn, Estonia, 13619
    • GSK Investigational Site
  • Tallinn, Estonia, 10138
    • GSK Investigational Site
  • Tartu, Estonia, 51014
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10367
    • GSK Investigational Site
  • Berlin, Germany, 10717
    • GSK Investigational Site
  • Berlin, Germany, 10787
    • GSK Investigational Site
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
      • GSK Investigational Site
    • Gelnhausen, Hessen, Germany, 63571
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • GSK Investigational Site
  • Schleswig-Holstein
    • Luebeck, Schleswig-Holstein, Germany, 23552
      • GSK Investigational Site
• Netherlands
  • Almelo, Netherlands, 7609 PP
    • GSK Investigational Site
  • Breda, Netherlands, 4819 EV
    • GSK Investigational Site
  • Eindhoven, Netherlands, 5623 EJ
    • GSK Investigational Site
  • Hoorn, Netherlands, 1624 NP
    • GSK Investigational Site
  • Veldhoven, Netherlands, 5504 DB
    • GSK Investigational Site
  • Zutphen, Netherlands, 7207 AE
    • GSK Investigational Site
• Romania
  • Bucharest, Romania, 050159
    • GSK Investigational Site
  • Bucharest, Romania, 020125
    • GSK Investigational Site
  • Iasi, Romania, 700115
    • GSK Investigational Site
  • Timisoara, Romania, 300310
    • GSK Investigational Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620109
    • GSK Investigational Site
  • Moscow, Russian Federation, 115446
    • GSK Investigational Site
  • Moscow, Russian Federation, 105 077
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 197022
    • GSK Investigational Site
  • Tomsk, Russian Federation, 634001
    • GSK Investigational Site
• Slovakia
  • Bratislava, Slovakia, 826 06
    • GSK Investigational Site
  • Kosice, Slovakia, 040 01
    • GSK Investigational Site
  • Nitra, Slovakia, 949 01
    • GSK Investigational Site
  • Nove Zamky, Slovakia, 940 01
    • GSK Investigational Site
  • Zvolen, Slovakia, 960 01
    • GSK Investigational Site
• South Africa
  • Bellville, South Africa, 7530
    • GSK Investigational Site
  • Durban, South Africa, 4001
    • GSK Investigational Site
  • Gatesville, South Africa, 7764
    • GSK Investigational Site
  • Mowbray, South Africa, 7700
    • GSK Investigational Site
  • Panorama, South Africa, 7500
    • GSK Investigational Site
  • Tygerberg, South Africa, 7505
    • GSK Investigational Site
• Sweden
  • Boden, Sweden, SE-961 64
    • GSK Investigational Site
  • Göteborg, Sweden, SE-413 45
    • GSK Investigational Site
  • Lund, Sweden, SE-221 85
    • GSK Investigational Site
  • Stockholm, Sweden, SE-171 76
    • GSK Investigational Site
• Ukraine
  • Dnipropetrovsk, Ukraine, 49074
    • GSK Investigational Site
  • Ivano-Frankivsk, Ukraine, 76018
    • GSK Investigational Site
  • Kharkiv, Ukraine, 61124
    • GSK Investigational Site
  • Kiev, Ukraine, 03680
    • GSK Investigational Site
  • Kyiv, Ukraine, 03680
    • GSK Investigational Site
  • Kyiv, Ukraine, 03115
    • GSK Investigational Site
  • Simferopol, Ukraine, 95043
    • GSK Investigational Site
  • Vinnytsia, Ukraine, 21029
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo arm
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: March 3, 2011
• First Submitted That Met QC Criteria: March 17, 2011
• First Posted (ESTIMATE): March 21, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): December 1, 2016
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: lung function; bronchodilator; COPD, dose response, dosing interval, efficacy, safety, PD, PK
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Salmeterol Xinafoate
• Other Study ID Numbers: 115032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 115032
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: 115032
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 115032
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 115032
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 115032
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 115032
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 115032
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register