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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Revefenacin; Drug: Formoterol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33155
      • Theravance Biopharma Investigational Site
    • Orlando, Florida, United States, 32825
      • Theravance Biopharma Investigational Site
    • Sarasota, Florida, United States, 34239
      • Theravance Biopharma Investigational Site
    • Tampa, Florida, United States, 33603
      • Theravance Biopharma Investigational Site
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • Theravance Biopharma Investigational Site
  • North Carolina
    • Monroe, North Carolina, United States, 28112
      • Theravance Biopharma Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Theravance Biopharma Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Theravance Biopharma Investigational Site
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16508
      • Theravance Biopharma Investigational Site
  • South Carolina
    • Gaffney, South Carolina, United States, 29341
      • Theravance Biopharma Investigational Site
    • Greenville, South Carolina, United States, 29615
      • Theravance Biopharma Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • Theravance Biopharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1: Revefenacin + Formoterol (Sequential); Days 1 to 21: Revefenacin and formoterol will be sequentially administered in the morning. Formoterol will be administered again in the evening.	Drug: Revefenacin; Revefenacin is administered via a nebulizer.; Other Names: TD-4208; Drug: Formoterol; Administered sequentially in both revefenacin and placebo arms using a nebulizer.
Experimental: Period 2: Revefenacin + Formoterol (Combo Solution); 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; Revefenacin is administered via a nebulizer.; Other Names: TD-4208; Drug: Formoterol; Administered sequentially in both revefenacin and placebo arms using a nebulizer.
Placebo Comparator: Period 1: Placebo + Formoterol (Sequential); 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: Formoterol; Administered sequentially in both revefenacin and placebo arms using a nebulizer.; Drug: Placebo; Placebo version of Revefenacin is administered via a nebulizer.
Placebo Comparator: Period 2: Placebo + Formoterol (Combo Solution); 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: Formoterol; Administered sequentially in both revefenacin and placebo arms using a nebulizer.; Drug: Placebo; Placebo version of Revefenacin is administered via a nebulizer.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Mylan Inc.
• Collaborators: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2018
• Primary Completion (Actual): September 25, 2018
• Study Completion (Actual): September 25, 2018

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: June 19, 2018
• First Posted (Actual): June 29, 2018

Study Record Updates

• Last Update Posted (Actual): February 24, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: COPD; Pulmonary Function; Chronic Obstructive Pulmonary Disease; Performist
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Formoterol Fumarate
• Other Study ID Numbers: 0167

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No