Trial Outcomes & Findings for An Efficacy Study of Umeclidinium/Vilanterol With Tiotropium/Olodaterol in COPD Patients (NCT NCT02799784)
NCT ID: NCT02799784
Last Updated: 2018-07-02
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
236 participants
Primary outcome timeframe
Week 8
Results posted on
2018-07-02
Participant Flow
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.
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).
Participant milestones
| Measure |
UMEC/VI Followed by TIO/OLO
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
|
TIO/OLO Followed by UMEC/VI
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
|
|---|---|---|
|
Treatment Period 1 (TP1- 8 Weeks)
STARTED
|
117
|
119
|
|
Treatment Period 1 (TP1- 8 Weeks)
COMPLETED
|
111
|
118
|
|
Treatment Period 1 (TP1- 8 Weeks)
NOT COMPLETED
|
6
|
1
|
|
Washout Period (3 Weeks)
STARTED
|
111
|
118
|
|
Washout Period (3 Weeks)
COMPLETED
|
111
|
118
|
|
Washout Period (3 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2 (TP2 - 8 Weeks)
STARTED
|
111
|
118
|
|
Treatment Period 2 (TP2 - 8 Weeks)
COMPLETED
|
110
|
115
|
|
Treatment Period 2 (TP2 - 8 Weeks)
NOT COMPLETED
|
1
|
3
|
Reasons for withdrawal
| Measure |
UMEC/VI Followed by TIO/OLO
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
|
TIO/OLO Followed by UMEC/VI
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
|
|---|---|---|
|
Treatment Period 1 (TP1- 8 Weeks)
Lost to Follow-up
|
1
|
1
|
|
Treatment Period 1 (TP1- 8 Weeks)
Withdrawal by Subject
|
5
|
0
|
|
Treatment Period 2 (TP2 - 8 Weeks)
Adverse Event
|
0
|
1
|
|
Treatment Period 2 (TP2 - 8 Weeks)
Par. reached protocol stopping criteria
|
1
|
0
|
|
Treatment Period 2 (TP2 - 8 Weeks)
Lost to Follow-up
|
0
|
1
|
|
Treatment Period 2 (TP2 - 8 Weeks)
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
An Efficacy Study of Umeclidinium/Vilanterol With Tiotropium/Olodaterol in COPD Patients
Baseline characteristics by cohort
| Measure |
All Treatment Combined
n=236 Participants
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
|
|---|---|
|
Age, Continuous
|
64.4 Years
STANDARD_DEVIATION 8.47 • n=5 Participants
|
|
Sex: Female, Male
Female
|
94 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
142 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
223 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 8Population: Per Protocol Population
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.
Outcome measures
| Measure |
Umeclidinium/Vilanterol 62.5/25 mcg
n=202 Participants
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
|
Tiotropium/Olodaterol 5/5 mcg
n=192 Participants
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
|
|---|---|---|
|
Trough Forced Expiratory Volume in One Second (FEV1) at Week 8
|
1.745 Liters
Standard Error 0.0131
|
1.692 Liters
Standard Error 0.0135
|
Adverse Events
Umeclidinium/Vilanterol 62.5/25 mcg
Serious events: 3 serious events
Other events: 19 other events
Deaths: 0 deaths
Tiotropium/Olodaterol 5/5 mcg
Serious events: 2 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Umeclidinium/Vilanterol 62.5/25 mcg
n=235 participants at risk
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
|
Tiotropium/Olodaterol 5/5 mcg
n=230 participants at risk
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
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/235 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
0.43%
1/230 • Number of events 1 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
|
Gastrointestinal disorders
Catheter site haemorrhage
|
0.00%
0/235 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
0.43%
1/230 • Number of events 1 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.43%
1/235 • Number of events 1 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
0.00%
0/230 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/235 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
0.43%
1/230 • Number of events 1 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
|
0.43%
1/235 • Number of events 1 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
0.00%
0/230 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
|
Nervous system disorders
Neuropathy peripheral
|
0.43%
1/235 • Number of events 1 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
0.00%
0/230 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
Other adverse events
| Measure |
Umeclidinium/Vilanterol 62.5/25 mcg
n=235 participants at risk
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
|
Tiotropium/Olodaterol 5/5 mcg
n=230 participants at risk
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
|
|---|---|---|
|
Infections and infestations
Viral upper respiratory tract infection
|
4.7%
11/235 • Number of events 11 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
6.1%
14/230 • Number of events 15 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
|
Infections and infestations
Upper respiratory tract infection
|
3.4%
8/235 • Number of events 8 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
3.0%
7/230 • Number of events 7 • On-therapy Serious Adverse Events (SAEs) and non-SAEs were collected from the start of study treatment and until follow up visit (Week 22).
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
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER