Trial Outcomes & Findings for Phase 4 COPD and Suboptimal Inspiratory Flow Rate (NCT NCT05165485)
NCT ID: NCT05165485
Last Updated: 2024-12-20
Results Overview
Change from baseline in forced expiratory volume in one second (FEV1) at trough on Day 85
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
404 participants
Primary outcome timeframe
Baseline, Day 85 following 84 days of dosing
Results posted on
2024-12-20
Participant Flow
Participant milestones
| Measure |
Tiotropium
Active Tiotropium and Placebo for Revefenacin.
Tiotropium: Tiotropium administered via Spiriva HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
|
Revefenacin
Active Revefenacin and Placebo for Tiotropium.
Revefenacin: Revefenacin administered via nebulization. Placebo for Tiotropium: Placebo administered as double blind, double dummy via HandiHaler® device.
|
|---|---|---|
|
Overall Study
STARTED
|
191
|
190
|
|
Overall Study
COMPLETED
|
156
|
147
|
|
Overall Study
NOT COMPLETED
|
35
|
43
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase 4 COPD and Suboptimal Inspiratory Flow Rate
Baseline characteristics by cohort
| Measure |
Tiotropium
n=191 Participants
Active Tiotropium and Placebo for Revefenacin. Tiotropium: Tiotropium administered via Spiriva HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
|
Revefenacin
n=189 Participants
Active Revefenacin and Placebo for Tiotropium. Revefenacin: Revefenacin administered via nebulization. Placebo for Tiotropium: Placebo administered as double blind, double dummy via HandiHaler® device.
|
Total
n=380 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66 years
n=5 Participants
|
67 years
n=7 Participants
|
66 years
n=5 Participants
|
|
Age, Customized
40 to 64 years old
|
81 Participants
n=5 Participants
|
79 Participants
n=7 Participants
|
160 Participants
n=5 Participants
|
|
Age, Customized
65 years old and over
|
110 Participants
n=5 Participants
|
110 Participants
n=7 Participants
|
220 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
86 Participants
n=5 Participants
|
90 Participants
n=7 Participants
|
176 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
105 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
204 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
176 Participants
n=5 Participants
|
172 Participants
n=7 Participants
|
348 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
175 Participants
n=5 Participants
|
171 Participants
n=7 Participants
|
346 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
191 Participants
n=5 Participants
|
189 Participants
n=7 Participants
|
380 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 85 following 84 days of dosingPopulation: All participants who received study treatment
Change from baseline in forced expiratory volume in one second (FEV1) at trough on Day 85
Outcome measures
| Measure |
Tiotropium
n=191 Participants
Active Tiotropium and Placebo for Revefenacin. Tiotropium: Tiotropium administered via Spiriva HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
|
Revefenacin
n=189 Participants
Active Revefenacin and Placebo for Tiotropium. Revefenacin: Revefenacin administered via nebulization. Placebo for Tiotropium: Placebo administered as double blind, double dummy via HandiHaler® device.
|
|---|---|---|
|
FEV1
|
101 mL
Standard Error 17
|
78 mL
Standard Error 17
|
SECONDARY outcome
Timeframe: Baseline, Day 30, Day 60, Day 85Population: All participants who received study treatment
Trough Overall Treatment Effect (OTE) on FEV1. Overall is defined as the average change from baseline at trough across Day 30, Day 60, and Day 85.
Outcome measures
| Measure |
Tiotropium
n=191 Participants
Active Tiotropium and Placebo for Revefenacin. Tiotropium: Tiotropium administered via Spiriva HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
|
Revefenacin
n=189 Participants
Active Revefenacin and Placebo for Tiotropium. Revefenacin: Revefenacin administered via nebulization. Placebo for Tiotropium: Placebo administered as double blind, double dummy via HandiHaler® device.
|
|---|---|---|
|
OTE on FEV1
|
87 mL
Standard Error 15
|
78 mL
Standard Error 15
|
SECONDARY outcome
Timeframe: Baseline, Day 30Population: All participants who received study treatment
Change from baseline in FEV1 at trough on Day 30
Outcome measures
| Measure |
Tiotropium
n=191 Participants
Active Tiotropium and Placebo for Revefenacin. Tiotropium: Tiotropium administered via Spiriva HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
|
Revefenacin
n=189 Participants
Active Revefenacin and Placebo for Tiotropium. Revefenacin: Revefenacin administered via nebulization. Placebo for Tiotropium: Placebo administered as double blind, double dummy via HandiHaler® device.
|
|---|---|---|
|
FEV1
|
81 mL
Standard Error 16
|
83 mL
Standard Error 16
|
SECONDARY outcome
Timeframe: Baseline, Day 60Population: All participants who received study treatment
Change from baseline in FEV1 at trough on Day 60
Outcome measures
| Measure |
Tiotropium
n=191 Participants
Active Tiotropium and Placebo for Revefenacin. Tiotropium: Tiotropium administered via Spiriva HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
|
Revefenacin
n=189 Participants
Active Revefenacin and Placebo for Tiotropium. Revefenacin: Revefenacin administered via nebulization. Placebo for Tiotropium: Placebo administered as double blind, double dummy via HandiHaler® device.
|
|---|---|---|
|
FEV1
|
79 mL
Standard Error 17
|
73 mL
Standard Error 17
|
SECONDARY outcome
Timeframe: Baseline, Day 85Population: All participants who received study treatment
Change from baseline in forced vital capacity (FVC) at trough on Day 85
Outcome measures
| Measure |
Tiotropium
n=191 Participants
Active Tiotropium and Placebo for Revefenacin. Tiotropium: Tiotropium administered via Spiriva HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
|
Revefenacin
n=189 Participants
Active Revefenacin and Placebo for Tiotropium. Revefenacin: Revefenacin administered via nebulization. Placebo for Tiotropium: Placebo administered as double blind, double dummy via HandiHaler® device.
|
|---|---|---|
|
FVC
|
198 mL
Standard Error 35
|
156 mL
Standard Error 35
|
SECONDARY outcome
Timeframe: Baseline, Day 85Population: All participants who received study treatment
Participants with an 80-mL or greater change from baseline FEV1 at trough were counted as responders. Participants with change from baseline FEV1 \< 80 mL and participants with change from baseline FEV1 not obtained were counted as nonresponders.
Outcome measures
| Measure |
Tiotropium
n=191 Participants
Active Tiotropium and Placebo for Revefenacin. Tiotropium: Tiotropium administered via Spiriva HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
|
Revefenacin
n=189 Participants
Active Revefenacin and Placebo for Tiotropium. Revefenacin: Revefenacin administered via nebulization. Placebo for Tiotropium: Placebo administered as double blind, double dummy via HandiHaler® device.
|
|---|---|---|
|
80-mL Increase in FEV1 at Trough on Day 85
|
83 Participants
|
63 Participants
|
SECONDARY outcome
Timeframe: Date of first dose through date of last dose + 7 daysPopulation: All participants who received study treatment and were evaluable for rescue medication use (i.e., were not using nebulized albuterol for rescue or albuterol 4 times daily for maintenance)
Count of participants experiencing events and time from first dose to first occurrence of a composite endpoint for exacerbations of COPD (CompEx) event were evaluated. The statistical analysis is a Cox proportional hazards model analysis of time to first event and the Revefenacin / Tiotropium hazard ratio is calculated and reported. Data are reported as the numbers of subjects with events and the hazard ratio is included in the Statistical Analysis section attached to the Outcome Measure data table. CompEx events are a composite of moderate or severe COPD exacerbation, premature termination from the study for any reason other than Sponsor decision, and clinically relevant deterioration in COPD. Clinically relevant deterioration events are defined as increases in COPD symptoms meeting specified criteria based on participant diary data.
Outcome measures
| Measure |
Tiotropium
n=174 Participants
Active Tiotropium and Placebo for Revefenacin. Tiotropium: Tiotropium administered via Spiriva HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
|
Revefenacin
n=176 Participants
Active Revefenacin and Placebo for Tiotropium. Revefenacin: Revefenacin administered via nebulization. Placebo for Tiotropium: Placebo administered as double blind, double dummy via HandiHaler® device.
|
|---|---|---|
|
First Occurrence of CompEx Event
|
56 Participants
|
58 Participants
|
Adverse Events
Tiotropium
Serious events: 15 serious events
Other events: 33 other events
Deaths: 0 deaths
Revefenacin
Serious events: 16 serious events
Other events: 38 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tiotropium
n=191 participants at risk
Tiotropium administered with Revefenacin Placebo
Tiotropium: Tiotropium 18 mcg administered once daily for 84 days via Spiriva HandiHaler®
Revefenacin Placebo: Placebo for Revefenacin administered once daily for 84 days via nebulization
|
Revefenacin
n=189 participants at risk
Revefenacin administered with Tiotropium Placebo
Revefenacin: Revefenacin 175 mcg administered once daily for 84 days via nebulization
Tiotropium Placebo: Placebo for Tiotropium administered once daily for 84 days via Spiriva HandiHaler®
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
1.6%
3/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Cardiac disorders
Chronic left ventricular failure
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Gastrointestinal disorders
Incarcerated inguinal hernia
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Infections and infestations
COVID-19
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
1.1%
2/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Infections and infestations
COVID-19 pneumonia
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Infections and infestations
Pneumonia
|
1.0%
2/191 • Day 1 through 7 days after the date of the last study drug dose.
|
1.1%
2/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Infections and infestations
Pneumonia legionella
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Infections and infestations
Urosepsis
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Renal and urinary disorders
Acute kidney injury
|
1.0%
2/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.1%
4/191 • Day 1 through 7 days after the date of the last study drug dose.
|
2.1%
4/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.00%
0/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/191 • Day 1 through 7 days after the date of the last study drug dose.
|
0.53%
1/189 • Day 1 through 7 days after the date of the last study drug dose.
|
Other adverse events
| Measure |
Tiotropium
n=191 participants at risk
Tiotropium administered with Revefenacin Placebo
Tiotropium: Tiotropium 18 mcg administered once daily for 84 days via Spiriva HandiHaler®
Revefenacin Placebo: Placebo for Revefenacin administered once daily for 84 days via nebulization
|
Revefenacin
n=189 participants at risk
Revefenacin administered with Tiotropium Placebo
Revefenacin: Revefenacin 175 mcg administered once daily for 84 days via nebulization
Tiotropium Placebo: Placebo for Tiotropium administered once daily for 84 days via Spiriva HandiHaler®
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
2.1%
4/191 • Day 1 through 7 days after the date of the last study drug dose.
|
1.1%
2/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Infections and infestations
COVID-19
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
1.6%
3/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Infections and infestations
Cellulitis
|
0.52%
1/191 • Day 1 through 7 days after the date of the last study drug dose.
|
1.6%
3/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Infections and infestations
Nasopharyngitis
|
1.0%
2/191 • Day 1 through 7 days after the date of the last study drug dose.
|
1.6%
3/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Infections and infestations
Upper respiratory tract infection
|
1.0%
2/191 • Day 1 through 7 days after the date of the last study drug dose.
|
1.6%
3/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.0%
2/191 • Day 1 through 7 days after the date of the last study drug dose.
|
2.1%
4/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Nervous system disorders
Headache
|
2.6%
5/191 • Day 1 through 7 days after the date of the last study drug dose.
|
1.1%
2/189 • Day 1 through 7 days after the date of the last study drug dose.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
11.5%
22/191 • Day 1 through 7 days after the date of the last study drug dose.
|
11.6%
22/189 • Day 1 through 7 days after the date of the last study drug dose.
|
Additional Information
Head of Clinical Development & Medical Affairs
Theravance Biopharma
Phone: 1-855-633-8479
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER