A 42-day Parallel Group Safety Study of Revefenacin and Formoterol, Administered in Sequence and as a Combination, in Participants With COPD

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3b, 42-day, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Safety and Tolerability of Nebulized Revefenacin and Nebulized Formoterol Fumarate (PERFOROMIST®) Administered in Sequence and as a Combined Solution in Subjects With Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Revefenacin
* Drug: Placebo
* Drug: Formoterol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1: Revefenacin + Formoterol (Sequential)<br>Days 1 to 21: Revefenacin and formoterol will be sequentially administered in the morning. Formoterol will be administered again in the evening. | Drug: Revefenacin<br>* Revefenacin is administered via a nebulizer.<br>* Other names: TD-4208;Drug: Formoterol<br>* Administered sequentially in both revefenacin and placebo arms using a nebulizer.<br>|
| Experimental: Period 2: Revefenacin + Formoterol (Combo Solution)<br>Days 22 to 42: After a 21 day period, the participants from the Revefenacin + Formoterol (Sequential) Arm will be dosed for 21 days with a combination of revefenacin and formoterol administered as a combined solution. Formoterol will be administered again in the evening. | Drug: Revefenacin<br>* Revefenacin is administered via a nebulizer.<br>* Other names: TD-4208;Drug: Formoterol<br>* Administered sequentially in both revefenacin and placebo arms using a nebulizer.<br>|
| Placebo Comparator: Period 1: Placebo + Formoterol (Sequential)<br>Days 1 to 21: Placebo versions of revefenacin and formoterol will be sequentially administered in the morning. Formoterol will be administered again in the evening. | Drug: Placebo<br>* Placebo version of Revefenacin is administered via a nebulizer.<br>Drug: Formoterol<br>* Administered sequentially in both revefenacin and placebo arms using a nebulizer.<br>|
| Placebo Comparator: Period 2: Placebo + Formoterol (Combo Solution)<br>Days 22 to 42: After a 21 day period, the participants from Placebo + Formoterol (Sequential) Arm the will be dosed for 21 days with a combination of placebo revefenacin and formoterol administered as a combined solution. Formoterol will be administered again in the evening. | Drug: Placebo<br>* Placebo version of Revefenacin is administered via a nebulizer.<br>Drug: Formoterol<br>* Administered sequentially in both revefenacin and placebo arms using a nebulizer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days) | 
| 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. | Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days) | 
| 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. | Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days) | 
| 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. | Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days) | 
| Number of Participants With Clinically Relevant Changes in Electrocardiogram Results | Clinically relevant changes identified based on change from baseline. | Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Chronic Obstructive Pulmonary Disease, Pulmonary Function, Performist