Chronic Obstructive Pulmonary Disease, COPD, Low Peak Inspiratory Flow Rate (PIFR)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD, Low Peak Inspiratory Flow Rate (PIFR)
Brief summary
This study is a randomized, double-blind, double-dummy, parallel group study to compare once daily nebulized Revefenacin with Spiriva once daily delivered via the HandiHaler® on lung function in subjects with COPD and a Low Peak Inspiratory Flow Rate.
Interventions
DRUGRevefenacin
Revefenacin administered via nebulization.
COMBINATION_PRODUCTSpiriva Handihaler®
Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device.
DRUGPlacebo for Revefenacin
Placebo administered as double blind, double dummy via nebulization.
DRUGPlacebo for Spiriva Handihaler®
Placebo administered as double blind, double dummy via Spiriva HandiHaler®.
Sponsors
Theravance Biopharma
Mylan Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is a male or female subject 40 years of age or older with a diagnosis of COPD. * Subject has a current or past cigarette smoking history (or equivalent for cigar or pipe smoking history) of at least 10 pack-years. * Subject is willing and able to provide signed and dated written informed consent to participate prior to initiation of any study related procedures.
Exclusion criteria
* Subject has a concurrent disease or condition that, in the opinion of the investigator, would interfere with continued study participation or confound the evaluation of safety and tolerability of the study drug. * Subject has a history of reactions or hypersensitivity to inhaled or nebulized anticholinergics. * Subject suffers from any medical condition that would preclude the use of inhaled anticholinergics, including narrow-angle glaucoma, symptomatic benign prostatic hyperplasia, bladder neck obstruction, or urinary retention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough FEV1 on Day 29 | Baseline and Day 29 | FEV1 = forced expiratory volume at one second |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline Trough FVC (Forced Vital Capacity) on Day 29 | Baseline and Day 29 |
| Change From Baseline Trough Inspiratory Capacity (IC) on Day 29 | Baseline and Day 29 |
| Change From Baseline Peak FEV1 on Day 29 | Baseline and Day 29 (0-4 hours) |
| Change From Baseline Peak FVC on Day 29 | Baseline and Day 29 (0-4 hours) |
| Summary of Rescue Medication Use: Puffs Per Day | 1 Month |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Revefenacin Active Revefenacin and placebo (in place of Spiriva Handihaler®)
Revefenacin: Revefenacin administered via nebulization.
Placebo for Spiriva Handihaler®: Placebo administered as double blind, double dummy via Spiriva HandiHaler®. | 102 |
| Spiriva Handihaler® Active Spiriva Handihaler® and placebo (in place of Revefenacin)
Spiriva Handihaler®: Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device.
Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization. | 104 |
| Total | 206 |
Baseline characteristics
| Characteristic | Revefenacin | Spiriva Handihaler® | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 51 Participants | 102 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants | 53 Participants | 104 Participants |
| Age, Continuous | 65.1 years STANDARD_DEVIATION 7.94 | 65.1 years STANDARD_DEVIATION 8.36 | 65.1 years STANDARD_DEVIATION 8.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 101 Participants | 197 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 9 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 90 Participants | 95 Participants | 185 Participants |
| Region of Enrollment United States | 102 Participants | 104 Participants | 206 Participants |
| Sex: Female, Male Female | 42 Participants | 40 Participants | 82 Participants |
| Sex: Female, Male Male | 60 Participants | 64 Participants | 124 Participants |
| Smoking history Current Smoker | 46 Participants | 50 Participants | 96 Participants |
| Smoking history Former Smoker | 56 Participants | 54 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 103 | 0 / 104 |
| other Total, other adverse events | 5 / 103 | 21 / 104 |
| serious Total, serious adverse events | 0 / 103 | 1 / 104 |
Outcome results
Primary
Change From Baseline in Trough FEV1 on Day 29
FEV1 = forced expiratory volume at one second
Time frame: Baseline and Day 29
Population: Intent-to-treat (ITT) analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Revefenacin | Change From Baseline in Trough FEV1 on Day 29 | 63.0 mL | Standard Error 20.17 |
| Spiriva Handihaler® | Change From Baseline in Trough FEV1 on Day 29 | 47.3 mL | Standard Error 19.06 |
Secondary
Change From Baseline Peak FEV1 on Day 29
Time frame: Baseline and Day 29 (0-4 hours)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Revefenacin | Change From Baseline Peak FEV1 on Day 29 | 174.2 mL | Standard Error 18.7 |
| Spiriva Handihaler® | Change From Baseline Peak FEV1 on Day 29 | 197.7 mL | Standard Error 17.73 |
Secondary
Change From Baseline Peak FVC on Day 29
Time frame: Baseline and Day 29 (0-4 hours)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Revefenacin | Change From Baseline Peak FVC on Day 29 | 354.2 mL | Standard Error 37.35 |
| Spiriva Handihaler® | Change From Baseline Peak FVC on Day 29 | 340.1 mL | Standard Error 35.49 |
Secondary
Change From Baseline Trough FVC (Forced Vital Capacity) on Day 29
Time frame: Baseline and Day 29
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Revefenacin | Change From Baseline Trough FVC (Forced Vital Capacity) on Day 29 | 125.4 mL | Standard Error 38.75 |
| Spiriva Handihaler® | Change From Baseline Trough FVC (Forced Vital Capacity) on Day 29 | 55.8 mL | Standard Error 36.62 |
Secondary
Change From Baseline Trough Inspiratory Capacity (IC) on Day 29
Time frame: Baseline and Day 29
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Revefenacin | Change From Baseline Trough Inspiratory Capacity (IC) on Day 29 | 71.4 mL | Standard Error 42.33 |
| Spiriva Handihaler® | Change From Baseline Trough Inspiratory Capacity (IC) on Day 29 | 84.1 mL | Standard Error 40.02 |
Secondary
Summary of Rescue Medication Use: Puffs Per Day
Time frame: 1 Month
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Revefenacin | Summary of Rescue Medication Use: Puffs Per Day | 3.4 puffs per day | Standard Error 0.42 |
| Spiriva Handihaler® | Summary of Rescue Medication Use: Puffs Per Day | 2.9 puffs per day | Standard Error 0.41 |