Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, Pulmonary Function, COPD, Performist
Brief summary
The primary objective of the study was to characterize the safety and tolerability of once-daily revefenacin inhalation solution when dosed sequentially with twice-daily formoterol inhalation solution (PERFOROMIST®) compared to PERFOROMIST®, in a population of participants with moderate-to-very severe Chronic Obstructive Pulmonary Disease (COPD) over 21 days.
Interventions
DRUGRevefenacin
Revefenacin is administered via a nebulizer.
DRUGPlacebo
Placebo version of Revefenacin is administered via a nebulizer.
DRUGFormoterol
Administered sequentially in both revefenacin and placebo arms using a nebulizer.
Sponsors
Theravance Biopharma
Mylan Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a randomized, double-blind, placebo-controlled, parallel-group study. Each participant will receive treatment daily for a total of 42 days. One group will receive placebo and formoterol and one group will receive revefenacin and formoterol.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is a male or female subject 40 years of age or older. * Participant is willing and able to provide signed and dated written informed consent. * Participant has a current or past cigarette smoking history (or equivalent for cigar or pipe smoking history) of at least 10 pack-years. * Participant must be willing and able to attend study visits according to the visit schedule and adhere to all study assessments/procedures.
Exclusion criteria
* Participant has a concurrent disease or condition that, in the opinion of the investigator, would interfere with study participation or confound the evaluation of safety, tolerability, or pharmacokinetics of the study drug. * Participant has a history of reactions or hypersensitivity to inhaled or nebulized anticholinergics, short-acting beta-agonists and long-acting beta-agonists. * Participant with clinically significant and uncontrolled hypertension, hypercholesterolemia or Type II diabetes mellitus, as assessed by the investigator. * Participant is unwilling or unable to stop the use of prohibited medications during the washout (if required) and treatment period and follow-up period of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event | Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days) | An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE is an AE that occurred after the participant has received the study drug. |
| Number of Participants Who Experienced at Least One Serious Treatment-Emergent Adverse Event | Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days) | A serious adverse event (SAE) was defined as any untoward medical occurrence occurring at any dose that resulted in any of the following outcomes: * Death * Life-threatening situation. Life-threatening refers to a situation in which the participant was at risk of death at the time of the event; it does not refer to an event which might have caused death if it were more severe * Inpatient hospitalization or prolongation of existing hospitalization * Congenital anomaly in the offspring of a participant who received study drug * Important medical events that may not result in death, be immediately life-threatening, or require hospitalization, could have been considered an SAE when, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed in this definition A treatment-emergent SAE is an SAE that occurred after the participant has received the study drug. |
| Number of Participants With Clinically Relevant Changes in Vital Sign Measurements | Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days) | Clinically significant changes identified based on change from baseline. Vital signs measured included heart rate, systolic blood pressure and diastolic blood pressure. |
| Number of Participants With Clinically Relevant Changes in Clinical Laboratory Measurements | Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days) | Clinically relevant changes identified based on change from baseline. Laboratory Measures assessed included hematology and serum. |
| Number of Participants With Clinically Relevant Changes in Electrocardiogram Results | Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days) | Clinically relevant changes identified based on change from baseline. |
Countries
United States
Participant flow
Pre-assignment details
Participants were randomized 1:1 to one of two treatment groups and received treatment twice-daily for the two 21-day treatment periods. The participants in Arms 1 and 2 are the same (minus attrition), and the participants in Arms 3 and 4 are the same (minus attrition).
Participants by arm
| Arm | Count |
|---|---|
| Revefenacin + Formoterol Includes participants from Arm 1 (Day 1-21) and Arm 2 (Day 22-42). | 63 |
| Placebo + Formoterol Includes participants from Arm 3 (Day 1-21) and Arm 4 (Day 22-42). | 59 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo + Formoterol | Total | Revefenacin + Formoterol |
|---|---|---|---|
| Age, Continuous | 64.4 years STANDARD_DEVIATION 8.43 | 63.7 years STANDARD_DEVIATION 8.56 | 63.1 years STANDARD_DEVIATION 8.71 |
| Body Mass Index | 29.11 kg/m^2 STANDARD_DEVIATION 6.349 | 29.17 kg/m^2 STANDARD_DEVIATION 6.475 | 29.22 kg/m^2 STANDARD_DEVIATION 6.642 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 10 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 112 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 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 | 3 Participants | 5 Participants | 2 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 56 Participants | 116 Participants | 60 Participants |
| Region of Enrollment United States | 59 participants | 122 participants | 63 participants |
| Sex: Female, Male Female | 25 Participants | 53 Participants | 28 Participants |
| Sex: Female, Male Male | 34 Participants | 69 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 55 | 0 / 63 | 0 / 62 |
| other Total, other adverse events | 3 / 63 | 5 / 62 | 7 / 59 | 6 / 55 |
| serious Total, serious adverse events | 0 / 59 | 0 / 55 | 0 / 63 | 0 / 62 |
Outcome results
Primary
Number of Participants Who Experienced at Least One Serious Treatment-Emergent Adverse Event
A serious adverse event (SAE) was defined as any untoward medical occurrence occurring at any dose that resulted in any of the following outcomes: * Death * Life-threatening situation. Life-threatening refers to a situation in which the participant was at risk of death at the time of the event; it does not refer to an event which might have caused death if it were more severe * Inpatient hospitalization or prolongation of existing hospitalization * Congenital anomaly in the offspring of a participant who received study drug * Important medical events that may not result in death, be immediately life-threatening, or require hospitalization, could have been considered an SAE when, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed in this definition A treatment-emergent SAE is an SAE that occurred after the participant has received the study drug.
Time frame: Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)
Population: The populations for Arms 1 and 2 are made up of the same participants, however 4 participants dropped out prior to beginning Period 2. Similarly, the populations for Arms 3 and 4 are made up of the same participants, but one participant dropped out prior to beginning Period 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Revefenacin + Formoterol (Sequential) | Number of Participants Who Experienced at Least One Serious Treatment-Emergent Adverse Event | 0 Participants |
| Period 2: Revefenacin + Formoterol (Combo Solution) | Number of Participants Who Experienced at Least One Serious Treatment-Emergent Adverse Event | 0 Participants |
| Period 1: Placebo + Formoterol (Sequential) | Number of Participants Who Experienced at Least One Serious Treatment-Emergent Adverse Event | 0 Participants |
| Period 2: Placebo + Formoterol (Combo Solution) | Number of Participants Who Experienced at Least One Serious Treatment-Emergent Adverse Event | 0 Participants |
Primary
Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event
An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE is an AE that occurred after the participant has received the study drug.
Time frame: Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)
Population: The populations for Arms 1 and 2 are made up of the same participants, however 4 participants dropped out prior to beginning Period 2. Similarly, the populations for Arms 3 and 4 are made up of the same participants, but one participant dropped out prior to beginning Period 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Revefenacin + Formoterol (Sequential) | Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event | 7 Participants |
| Period 2: Revefenacin + Formoterol (Combo Solution) | Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event | 6 Participants |
| Period 1: Placebo + Formoterol (Sequential) | Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event | 3 Participants |
| Period 2: Placebo + Formoterol (Combo Solution) | Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event | 5 Participants |
Primary
Number of Participants With Clinically Relevant Changes in Clinical Laboratory Measurements
Clinically relevant changes identified based on change from baseline. Laboratory Measures assessed included hematology and serum.
Time frame: Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)
Population: The populations for Arms 1 and 2 are made up of the same participants, however 4 participants dropped out prior to beginning Period 2. Similarly, the populations for Arms 3 and 4 are made up of the same participants, but one participant dropped out prior to beginning Period 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Revefenacin + Formoterol (Sequential) | Number of Participants With Clinically Relevant Changes in Clinical Laboratory Measurements | 0 Participants |
| Period 2: Revefenacin + Formoterol (Combo Solution) | Number of Participants With Clinically Relevant Changes in Clinical Laboratory Measurements | 0 Participants |
| Period 1: Placebo + Formoterol (Sequential) | Number of Participants With Clinically Relevant Changes in Clinical Laboratory Measurements | 0 Participants |
| Period 2: Placebo + Formoterol (Combo Solution) | Number of Participants With Clinically Relevant Changes in Clinical Laboratory Measurements | 0 Participants |
Primary
Number of Participants With Clinically Relevant Changes in Electrocardiogram Results
Clinically relevant changes identified based on change from baseline.
Time frame: Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)
Population: The populations for Arms 1 and 2 are made up of the same participants, however 4 participants dropped out prior to beginning Period 2. Similarly, the populations for Arms 3 and 4 are made up of the same participants, but one participant dropped out prior to beginning Period 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Revefenacin + Formoterol (Sequential) | Number of Participants With Clinically Relevant Changes in Electrocardiogram Results | 0 Participants |
| Period 2: Revefenacin + Formoterol (Combo Solution) | Number of Participants With Clinically Relevant Changes in Electrocardiogram Results | 0 Participants |
| Period 1: Placebo + Formoterol (Sequential) | Number of Participants With Clinically Relevant Changes in Electrocardiogram Results | 0 Participants |
| Period 2: Placebo + Formoterol (Combo Solution) | Number of Participants With Clinically Relevant Changes in Electrocardiogram Results | 0 Participants |
Primary
Number of Participants With Clinically Relevant Changes in Vital Sign Measurements
Clinically significant changes identified based on change from baseline. Vital signs measured included heart rate, systolic blood pressure and diastolic blood pressure.
Time frame: Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)
Population: The populations for Arms 1 and 2 are made up of the same participants, however 4 participants dropped out prior to beginning Period 2. Similarly, the populations for Arms 3 and 4 are made up of the same participants, but one participant dropped out prior to beginning Period 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Revefenacin + Formoterol (Sequential) | Number of Participants With Clinically Relevant Changes in Vital Sign Measurements | 0 Participants |
| Period 2: Revefenacin + Formoterol (Combo Solution) | Number of Participants With Clinically Relevant Changes in Vital Sign Measurements | 0 Participants |
| Period 1: Placebo + Formoterol (Sequential) | Number of Participants With Clinically Relevant Changes in Vital Sign Measurements | 0 Participants |
| Period 2: Placebo + Formoterol (Combo Solution) | Number of Participants With Clinically Relevant Changes in Vital Sign Measurements | 0 Participants |