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A 12-week Study to Evaluate the Efficacy and Safety of Umeclidinium 62.5 Microgram (mcg) Compared With Glycopyrronium 44 mcg in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

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ClinicalTrials.gov Identifier: NCT02236611
Recruitment Status : Completed
First Posted : September 10, 2014
Results First Posted : February 15, 2016
Last Update Posted : May 2, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: Umeclidinium
Drug: Glycopyrronium
Enrollment 1036
Recruitment Details A total of 1290 par. were screened; 1037 par. were randomized and 1034 were in the ITT population which comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. Two par. were randomized in error and one par. was randomized, but did not take any study medication.
Pre-assignment Details Participants, with clinical history of chronic obstructive pulmonary disease, who meet the eligibility criteria at screening were enrolled in a 7 to 14 day run-in period. Participant meeting continuation criteria, during run-in period, were randomized (1:1) to receive umeclidinium or glycopyrronium.
Arm/Group Title UMEC 62.5 mcg QD GLYCO 44 mcg QD
Hide Arm/Group Description Participants received Umeclidinium (UMEC) inhalation powder 62.5 microgram (mcg) once-daily (QD) in morning via a novel dry powder inhaler (nDPI) for 12 weeks. Participants also received albuterol/salbutamol via metered-dose-inhaler (MDI) or nebules as needed throughout the study. Participants received glycopyrronium bromide (GLYCO) inhalation capsules 44 mcg QD in morning via an alternative dry powder inhaler (DPI) for 12 weeks. Participants also received albuterol/salbutamol via MDI or nebules as needed throughout the study.
Period Title: Overall Study
Started 516 518
Completed 490 484
Not Completed 26 34
Reason Not Completed
Adverse Event             10             16
Lack of Efficacy             4             7
Lost to Follow-up             0             2
Protocol deviation             3             5
Withdrew consent             9             4
Arm/Group Title UMEC 62.5 mcg QD GLYCO 44 mcg QD Total
Hide Arm/Group Description Participants received Umeclidinium (UMEC) inhalation powder 62.5 microgram (mcg) once-daily (QD) in morning via a novel dry powder inhaler (nDPI) for 12 weeks. Participants also received albuterol/salbutamol via metered-dose-inhaler (MDI) or nebules as needed throughout the study. Participants received glycopyrronium bromide (GLYCO) inhalation capsules 44 mcg QD in morning via an alternative dry powder inhaler (DPI) for 12 weeks. Participants also received albuterol/salbutamol via MDI or nebules as needed throughout the study. Total of all reporting groups
Overall Number of Baseline Participants 516 518 1034
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 516 participants 518 participants 1034 participants
64.1  (8.35) 64.0  (8.26) 64.1  (8.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 516 participants 518 participants 1034 participants
Female
161
  31.2%
168
  32.4%
329
  31.8%
Male
355
  68.8%
350
  67.6%
705
  68.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 516 participants 518 participants 1034 participants
Central/South Asian Heritage (HRTG) 3 0 3
Japanese/East Asian Heritage/South East Asian HRTG 0 1 1
White 513 517 1030
1.Primary Outcome
Title Change From Baseline in Trough FEV1 on Day 85
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 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Baseline trough FEV1 is the mean of the two assessments made -30 and -5 minutes (min) pre-dose on Day 1. Change from baseline was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis performed using a repeated measures model with covariates of treatment, baseline FEV1, centre group, 24 hour subset flag, Day, Day by baseline and Day by treatment interactions. The least squares mean changes are presented here.
Time Frame Baseline (BL) and Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol(PP) Population(pop): Participants(par) in the Intent-To-Treat pop who did not have a full protocol deviation considered to impact efficacy. Par represent those with data available at time point presented; however, all par. in the PP pop. without missing covariate information and >=1 post BL measurement are included in analysis
Arm/Group Title UMEC 62.5 mcg QD GLYCO 44 mcg QD
Hide Arm/Group Description:
Participants received Umeclidinium (UMEC) inhalation powder 62.5 microgram (mcg) once-daily (QD) in morning via a novel dry powder inhaler (nDPI) for 12 weeks. Participants also received albuterol/salbutamol via metered-dose-inhaler (MDI) or nebules as needed throughout the study.
Participants received glycopyrronium bromide (GLYCO) inhalation capsules 44 mcg QD in morning via an alternative dry powder inhaler (DPI) for 12 weeks. Participants also received albuterol/salbutamol via MDI or nebules as needed throughout the study.
Overall Number of Participants Analyzed 431 425
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.123  (0.0105) 0.099  (0.0105)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UMEC 62.5 mcg QD, GLYCO 44 mcg QD
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Alternate hypothesis: the difference between the trt means (umeclidinium minus glycopyrronium) would be > -50 milliliters (mL). If the lower CI (2.5% 1-sided significance level) of the statistical test should fall above -50 mL, then umeclidinium may be deemed statistically non-inferior to glycopyrronium. If the lower CI (2.5% 1-sided significance) of the statistical testing exceeded 0 then, umeclidinium may be deemed statistically superior to glycopyrronium.
Statistical Test of Hypothesis P-Value 0.100
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.024
Confidence Interval (2-Sided) 95%
-0.005 to 0.054
Estimation Comments [Not Specified]
Time Frame On-treatment(trt) non-serious adverse events(AEs) and serious AEs are events occurring while par were on trt or events with an onset during follow-up period(up to 13 weeks).
Adverse Event Reporting Description On-treatment SAEs and non-serious AEs were reported for the Intent-To Treat Population comprised all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
 
Arm/Group Title UMEC 62.5 mcg QD GLYCO 44 mcg QD
Hide Arm/Group Description Participants received Umeclidinium (UMEC) inhalation powder 62.5 microgram (mcg) once-daily (QD) in morning via a novel dry powder inhaler (nDPI) for 12 weeks. Participants also received albuterol/salbutamol via metered-dose-inhaler (MDI) or nebules as needed throughout the study. Participants received glycopyrronium bromide (GLYCO) inhalation capsules 44 mcg QD in morning via an alternative dry powder inhaler (DPI) for 12 weeks. Participants also received albuterol/salbutamol via MDI or nebules as needed throughout the study.
All-Cause Mortality
UMEC 62.5 mcg QD GLYCO 44 mcg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
UMEC 62.5 mcg QD GLYCO 44 mcg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   17/516 (3.29%)   15/518 (2.90%) 
Cardiac disorders     
Atrial fibrillation  1  1/516 (0.19%)  1/518 (0.19%) 
Acute coronary syndrome  1  0/516 (0.00%)  1/518 (0.19%) 
Cardiac failure  1  0/516 (0.00%)  1/518 (0.19%) 
Myocardial infarction  1  1/516 (0.19%)  0/518 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  0/516 (0.00%)  1/518 (0.19%) 
Mouth ulceration  1  1/516 (0.19%)  0/518 (0.00%) 
Rectal haemorrhage  1  0/516 (0.00%)  1/518 (0.19%) 
General disorders     
Sudden cardiac death  1  1/516 (0.19%)  0/518 (0.00%) 
Sudden death  1  1/516 (0.19%)  0/518 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  0/516 (0.00%)  1/518 (0.19%) 
Infections and infestations     
Pneumonia  1  2/516 (0.39%)  0/518 (0.00%) 
Urinary tract infection  1  0/516 (0.00%)  1/518 (0.19%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  1/516 (0.19%)  0/518 (0.00%) 
Femoral neck fracture  1  0/516 (0.00%)  1/518 (0.19%) 
Hip fracture  1  0/516 (0.00%)  1/518 (0.19%) 
Metabolism and nutrition disorders     
Hyponatraemia  1  0/516 (0.00%)  1/518 (0.19%) 
Musculoskeletal and connective tissue disorders     
Foot deformity  1  0/516 (0.00%)  1/518 (0.19%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Laryngeal cancer  1  0/516 (0.00%)  1/518 (0.19%) 
Neoplasm malignant  1  1/516 (0.19%)  0/518 (0.00%) 
Nervous system disorders     
Cerebrovascular accident  1  1/516 (0.19%)  0/518 (0.00%) 
Ischaemic stroke  1  1/516 (0.19%)  0/518 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  7/516 (1.36%)  5/518 (0.97%) 
Dyspnoea  1  0/516 (0.00%)  1/518 (0.19%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
UMEC 62.5 mcg QD GLYCO 44 mcg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   77/516 (14.92%)   80/518 (15.44%) 
Infections and infestations     
Nasopharyngitis  1  42/516 (8.14%)  39/518 (7.53%) 
Nervous system disorders     
Headache  1  42/516 (8.14%)  51/518 (9.85%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02236611     History of Changes
Other Study ID Numbers: 201315
First Submitted: September 8, 2014
First Posted: September 10, 2014
Results First Submitted: January 18, 2016
Results First Posted: February 15, 2016
Last Update Posted: May 2, 2018