Trial Outcomes & Findings for The Purpose of the This Study is to Evaluate the Spirometric Effect (Trough FEV1) of Umeclidinium/Vilanterol 62.5/25 mcg Once Daily Compared With Tiotropium 18mcg Once Daily Over a a 12-week Treatment Period in Subjects With COPD Who Continue to Have Symptoms on Tiotropium (NCT NCT01899742)

Last Updated: 2018-01-24

Results Overview

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in 1 second. BL was the mean of the values measured 23 hour and 24 hour after dosing prior to Day 1 (ie. after the last open label \[OL\] tiotropium dosing and prior to the randomized dose). Change from BL is defined as the post-BL value minus the BL value. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after dosing on Day 84 (at Week 12 + 1 day). Analysis performed using a mixed repeated measures model (MMRM) with covariates of treatment, BL, center group, 24 hour subset flag, Day, Day by BL and Day by treatment interactions. ITT Population is defined as participants who received at least one dose of randomized study medication in the treatment period. Only those participants with data available at the specified time point were included in the analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

497 participants

Primary outcome timeframe

Baseline (BL) and Day 85

Results posted on

2018-01-24

Participant Flow

Eligible participants (par) completed a 4-week open label tiotropium run-in phase, and were randomized to blinded study medication for 12 weeks. Supplemental albuterol/salbutamol was provided to all par, to be used on an as-needed basis during the run-in phase and up to Day 85.

A total of 739 par were enrolled; 496 par randomized and 494 par were included in the Intent-to-Treat (ITT) Population (Pop), comprised of all par randomized to treatment (trt) who received at least 1 dose of randomized study medication in the trt period.

Participant milestones

Participant milestones
Measure	Umeclidinium/Vilanterol 62.5/25 µg Participants self-administered one dose of umeclidinium/vilanterol inhalation powder 62.5/25 micrograms (µg) once daily via an ELLIPTA dry powder inhaler and placebo once daily via a HANDIHALER each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.	Tiotropium Bromide 18 µg Participants self-administered one dose of tiotropium bromide 18 µg once daily via a HANDIHALER and placebo once daily via an ELLIPTA dry powder inhaler each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.
Overall Study STARTED	247	247
Overall Study COMPLETED	230	231
Overall Study NOT COMPLETED	17	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Umeclidinium/Vilanterol 62.5/25 µg Participants self-administered one dose of umeclidinium/vilanterol inhalation powder 62.5/25 micrograms (µg) once daily via an ELLIPTA dry powder inhaler and placebo once daily via a HANDIHALER each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.	Tiotropium Bromide 18 µg Participants self-administered one dose of tiotropium bromide 18 µg once daily via a HANDIHALER and placebo once daily via an ELLIPTA dry powder inhaler each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.
Overall Study Adverse Event	5	4
Overall Study Lack of Efficacy	1	5
Overall Study Protocol Violation	2	2
Overall Study Withdrawal by Subject	9	5

Baseline Characteristics

The Purpose of the This Study is to Evaluate the Spirometric Effect (Trough FEV1) of Umeclidinium/Vilanterol 62.5/25 mcg Once Daily Compared With Tiotropium 18mcg Once Daily Over a a 12-week Treatment Period in Subjects With COPD Who Continue to Have Symptoms on Tiotropium

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Umeclidinium/Vilanterol 62.5/25 µg n=247 Participants Participants self-administered one dose of umeclidinium/vilanterol inhalation powder 62.5/25 µg once daily via an ELLIPTA dry powder inhaler and placebo once daily via a HANDIHALER each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.	Tiotropium Bromide 18 µg n=247 Participants Participants self-administered one dose of tiotropium bromide 18 µg once daily via a HANDIHALER and placebo once daily via an ELLIPTA dry powder inhaler each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.	Total n=494 Participants Total of all reporting groups
Age, Continuous	64.5 Years STANDARD_DEVIATION 8.71 • n=5 Participants	64.3 Years STANDARD_DEVIATION 8.74 • n=7 Participants	64.4 Years STANDARD_DEVIATION 8.71 • n=5 Participants
Sex: Female, Male Female	84 Participants n=5 Participants	87 Participants n=7 Participants	171 Participants n=5 Participants
Sex: Female, Male Male	163 Participants n=5 Participants	160 Participants n=7 Participants	323 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	239 Participants n=5 Participants	237 Participants n=7 Participants	476 Participants n=5 Participants
Race/Ethnicity, Customized White - Mixed Race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (BL) and Day 85

Population: ITT Population

Outcome measures

Outcome measures
Measure	Umeclidinium/Vilanterol 62.5/25 µg n=224 Participants Participants self-administered one dose of umeclidinium/vilanterol inhalation powder 62.5/25 µg once daily via an ELLIPTA dry powder inhaler and placebo once daily via a HANDIHALER each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.	Tiotropium Bromide 18 µg n=225 Participants Participants self-administered one dose of tiotropium bromide 18 µg once daily via a HANDIHALER and placebo once daily via an ELLIPTA dry powder inhaler each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85 (Visit 8)	0.074 Liters Standard Error 0.0155	-0.014 Liters Standard Error 0.0155

SECONDARY outcome

Timeframe: Baseline and Day 84

Population: ITT Population

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in 1 second. FEV1 assessments taken on 0 to 3 hour on Day 84 (pre-dose, 5 minutes (min), 15 min, 30 min, 1 hour, and 3 hour post-dose). Pre-dose was the reading obtained at 24 hours after the previous day's dose (Day 83 dose). BL is defined as mean of the values measured 23 hour and 24 hour after dosing prior to Day 1 (ie. after the last OL tiotropium dosing and prior to the randomized dose). Change from BL is defined as the post-BL value minus the BL value. Analysis performed using mixed model repeated measures with covariates of treatment, BL FEV1, center group, 24 hour subset flag, time, time by treatment interaction and time by BL interaction. Only those participants with data available at the specified time point were included in the analysis.

Outcome measures

Outcome measures
Measure	Umeclidinium/Vilanterol 62.5/25 µg n=225 Participants Participants self-administered one dose of umeclidinium/vilanterol inhalation powder 62.5/25 µg once daily via an ELLIPTA dry powder inhaler and placebo once daily via a HANDIHALER each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.	Tiotropium Bromide 18 µg n=228 Participants Participants self-administered one dose of tiotropium bromide 18 µg once daily via a HANDIHALER and placebo once daily via an ELLIPTA dry powder inhaler each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.
Change From BL in FEV1 at 3 Hours Postdose on Day 84	0.164 Liters Standard Error 0.0178	0.091 Liters Standard Error 0.0177

Adverse Events

Umeclidinium/Vilanterol 62.5/25 µg

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Tiotropium Bromide 18 µg

Serious events: 6 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Umeclidinium/Vilanterol 62.5/25 µg n=247 participants at risk Participants self-administered one dose of umeclidinium/vilanterol inhalation powder 62.5/25 µg once daily via an ELLIPTA dry powder inhaler and placebo once daily via a HANDIHALER each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.	Tiotropium Bromide 18 µg n=247 participants at risk Participants self-administered one dose of tiotropium bromide 18 µg once daily via a HANDIHALER and placebo once daily via an ELLIPTA dry powder inhaler each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.81% 2/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Cardiac disorders Myocardial infarction	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Cardiac disorders Atrial flutter	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Infections and infestations Pneumonia	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Infections and infestations Appendicitis	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Metabolism and nutrition disorders Dehydration	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Nervous system disorders Cerebrovascular accident	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Vascular disorders Hypotension	0.00% 0/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.

Other adverse events

Other adverse events
Measure	Umeclidinium/Vilanterol 62.5/25 µg n=247 participants at risk Participants self-administered one dose of umeclidinium/vilanterol inhalation powder 62.5/25 µg once daily via an ELLIPTA dry powder inhaler and placebo once daily via a HANDIHALER each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.	Tiotropium Bromide 18 µg n=247 participants at risk Participants self-administered one dose of tiotropium bromide 18 µg once daily via a HANDIHALER and placebo once daily via an ELLIPTA dry powder inhaler each morning for 12 weeks. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.
Infections and infestations Nasopharyngitis	7.3% 18/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	6.9% 17/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Nervous system disorders Headache	6.5% 16/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	7.3% 18/247 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 94 days starting from Day 1 of treatment until the follow-up contact. On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

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