Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Efficacy Study of Umeclidinium/Vilanterol With Tiotropium/Olodaterol in COPD Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02799784
Recruitment Status : Completed
First Posted : June 15, 2016
Results First Posted : July 2, 2018
Last Update Posted : July 2, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: UMEC/VI
Drug: TIO/OLO
Drug: Albuterol/salbutamol
Enrollment 236
Recruitment Details This is a multicenter, randomized, open label, 2 period crossover complete block design study. Participants (par.) with Chronic Obstructive Pulmonary Disease (COPD) were enrolled across 4 countries: Germany, Spain, the United Kingdom and the United States.
Pre-assignment Details Study consisted of a run-in period of approximately 2 weeks followed by two 8-week treatment periods with a washout of approximately 3 weeks. The total duration of the study was approximately 22 weeks including follow-up. A total of 443 par. were screened, of which 236 par. were randomized (207 par. were pre-screen, screen and run-in failures).
Arm/Group Title UMEC/VI Followed by TIO/OLO TIO/OLO Followed by UMEC/VI
Hide Arm/Group Description In this 2-way crossover study, eligible participants were administered Umeclidinium/Vilanterol (UMEC/VI) 62.5/25 microgram (mcg) (as one inhalation) once-daily (QD) via ELLIPTA Inhaler for 8 weeks in TP1. It was followed by a washout period of 3 weeks. Par. received Tiotropium/Olodaterol (TIO/OLO) 5/5 mcg inhalation spray as 2 inhalations of 2.5/2.5 mcg each via the RESPIMAT® inhaler for 8 weeks in TP2. Albuterol/salbutamol was supplied as an inhalation spray via metered dose inhaler throughout the study for use as-needed In this 2-way crossover study, eligible participants were administered TIO/OLO 5/5 mcg inhalation spray as 2 inhalations of 2.5/2.5 mcg each via the RESPIMAT® inhaler for 8 weeks in TP1. It was followed by a washout period of 3 weeks. Par. received UMEC/VI 62.5/25 mcg (as one inhalation) QD via ELLIPTA Inhaler for 8 weeks in TP2. Albuterol/salbutamol was supplied as an inhalation spray via metered dose inhaler throughout the study for use as-needed
Period Title: Treatment Period 1 (TP1- 8 Weeks)
Started 117 119
Completed 111 118
Not Completed 6 1
Reason Not Completed
Lost to Follow-up             1             1
Withdrawal by Subject             5             0
Period Title: Washout Period (3 Weeks)
Started 111 118
Completed 111 118
Not Completed 0 0
Period Title: Treatment Period 2 (TP2 - 8 Weeks)
Started 111 118
Completed 110 115
Not Completed 1 3
Reason Not Completed
Adverse Event             0             1
Par. reached protocol stopping criteria             1             0
Lost to Follow-up             0             1
Withdrawal by Subject             0             1
Arm/Group Title All Treatment Combined
Hide Arm/Group Description In this 2-way crossover study, eligible participants were randomized to receive UMEC/VI inhalation powder 62.5/25 mcg QD administered as 1 inhalation via the ELLIPTA® Inhaler and TIO/OLO 5/5 mcg inhalation spray administered as 2 inhalations via the RESPIMAT® inhaler in 8-week TP1 and TP2 per randomization. This was separated by a 3-week washout period. Albuterol/salbutamol was supplied as an inhalation spray via metered dose inhaler throughout the study for use as-needed
Overall Number of Baseline Participants 236
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 236 participants
64.4  (8.47)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 236 participants
Female
94
  39.8%
Male
142
  60.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 236 participants
African American/African Heritage
13
   5.5%
White - White/Caucasian/European Heritage
223
  94.5%
1.Primary Outcome
Title Trough Forced Expiratory Volume in One Second (FEV1) at Week 8
Hide Description FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 was defined as 23 and 24 hour post-dose FEV1 measurements. All par. in the Intent To Treat (ITT) Population who were not identified as full protocol deviators were included in Per-Protocol (PP) Population. ITT Population, comprised of all randomized subjects, who received at least one dose of study medication.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Population
Arm/Group Title Umeclidinium/Vilanterol 62.5/25 mcg Tiotropium/Olodaterol 5/5 mcg
Hide Arm/Group Description:
Eligible par. were administered Umeclidinium/Vilanterol (UMEC/VI) 62.5/25 mcg (as one inhalation) once-daily (QD) via the ELLIPTA Inhaler for 8 weeks followed by a washout period of 3 weeks in period-1 or 2 as per randomization. Albuterol/salbutamol was supplied as an inhalation spray via metered dose inhaler throughout the study for use as-needed
Eligible par. were administered Tiotropium/Olodaterol (TIO/OLO) 5/5 mcg inhalation spray as 2 inhalations of 2.5/2.5 mcg each via the RESPIMAT® inhaler for 8 weeks followed by a washout period of 3 weeks in period-1 or 2 as per randomization. Albuterol/salbutamol was supplied as an inhalation spray via metered dose inhaler throughout the study for use as-needed
Overall Number of Participants Analyzed 202 192
Least Squares Mean (Standard Error)
Unit of Measure: Liters
1.745  (0.0131) 1.692  (0.0135)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Umeclidinium/Vilanterol 62.5/25 mcg, Tiotropium/Olodaterol 5/5 mcg
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments If the lower bound of the two-sided 95% confidence interval around the (UMEC/VI 62.5/25 mcg versus TIO/OLO 5/5 mcg) treatment difference is above -50 milliliter then UMEC/VI 62.5/25 mcg was to be considered non-inferior to TIO/OLO 5/5 mcg.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.053
Confidence Interval (2-Sided) 95%
0.026 to 0.080
Estimation Comments [Not Specified]
Time Frame On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
Adverse Event Reporting Description On-therapy SAEs and non-SAEs are reported for ITT Population, comprised of all randomized participants, who received at least one dose of study medication
 
Arm/Group Title Umeclidinium/Vilanterol 62.5/25 mcg Tiotropium/Olodaterol 5/5 mcg
Hide Arm/Group Description Eligible par. were administered Umeclidinium/Vilanterol (UMEC/VI) 62.5/25 mcg (as one inhalation) once-daily (QD) via the ELLIPTA Inhaler for 8 weeks followed by a washout period of 3 weeks in period-1 or 2 as per randomization. Albuterol/salbutamol was supplied as an inhalation spray via metered dose inhaler throughout the study for use as-needed Eligible par. were administered Tiotropium/Olodaterol (TIO/OLO) 5/5 mcg inhalation spray as 2 inhalations of 2.5/2.5 mcg each via the RESPIMAT® inhaler for 8 weeks followed by a washout period of 3 weeks in period-1 or 2 as per randomization. Albuterol/salbutamol was supplied as an inhalation spray via metered dose inhaler throughout the study for use as-needed
All-Cause Mortality
Umeclidinium/Vilanterol 62.5/25 mcg Tiotropium/Olodaterol 5/5 mcg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/235 (0.00%)      0/230 (0.00%)    
Hide Serious Adverse Events
Umeclidinium/Vilanterol 62.5/25 mcg Tiotropium/Olodaterol 5/5 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/235 (1.28%)      2/230 (0.87%)    
Cardiac disorders     
Acute myocardial infarction  1  0/235 (0.00%)  0 1/230 (0.43%)  1
Gastrointestinal disorders     
Catheter site haemorrhage  1  0/235 (0.00%)  0 1/230 (0.43%)  1
Injury, poisoning and procedural complications     
Rib fracture  1  1/235 (0.43%)  1 0/230 (0.00%)  0
Metabolism and nutrition disorders     
Hyperglycaemia  1  0/235 (0.00%)  0 1/230 (0.43%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hepatocellular carcinoma  1  1/235 (0.43%)  1 0/230 (0.00%)  0
Nervous system disorders     
Neuropathy peripheral  1  1/235 (0.43%)  1 0/230 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Umeclidinium/Vilanterol 62.5/25 mcg Tiotropium/Olodaterol 5/5 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/235 (8.09%)      21/230 (9.13%)    
Infections and infestations     
Viral upper respiratory tract infection  1  11/235 (4.68%)  11 14/230 (6.09%)  15
Upper respiratory tract infection  1  8/235 (3.40%)  8 7/230 (3.04%)  7
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02799784    
Other Study ID Numbers: 204990
First Submitted: June 2, 2016
First Posted: June 15, 2016
Results First Submitted: April 3, 2018
Results First Posted: July 2, 2018
Last Update Posted: July 2, 2018