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

• ClinicalTrials.gov Identifier: NCT03573817
• Recruitment Status: Completed
• First Posted: June 29, 2018
• Results First Posted: December 18, 2019
• Last Update Posted: February 24, 2022
• Sponsor: Mylan Inc.
• Collaborator: Theravance Biopharma
• Information provided by (Responsible Party): Viatris Inc. ( Mylan Inc. )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: Revefenacin; Drug: Placebo; Drug: Formoterol	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 31, 2018
• Actual Primary Completion Date: September 25, 2018
• Actual Study Completion Date: September 25, 2018

Arms and Interventions

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 Name: 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 Name: 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: Placebo; Placebo version of Revefenacin is administered via a nebulizer.; Drug: Formoterol; Administered sequentially in both revefenacin and placebo arms using 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: Placebo; Placebo version of Revefenacin is administered via a nebulizer.; Drug: Formoterol; Administered sequentially in both revefenacin and placebo arms using a nebulizer.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event [ Time Frame: 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.
2. Number of Participants Who Experienced at Least One Serious Treatment-Emergent Adverse Event [ Time Frame: 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.

3. Number of Participants With Clinically Relevant Changes in Vital Sign Measurements [ Time Frame: 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.
4. Number of Participants With Clinically Relevant Changes in Clinical Laboratory Measurements [ Time Frame: 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.
5. Number of Participants With Clinically Relevant Changes in Electrocardiogram Results [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Theravance Biopharma Investigational Site

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

United States, Missouri

Theravance Biopharma Investigational Site

Saint Charles, Missouri, United States, 63301

United States, North Carolina

Theravance Biopharma Investigational Site

Monroe, North Carolina, United States, 28112

United States, Ohio

Theravance Biopharma Investigational Site

Columbus, Ohio, United States, 43213

United States, Oregon

Theravance Biopharma Investigational Site

Medford, Oregon, United States, 97504

United States, Pennsylvania

Theravance Biopharma Investigational Site

Erie, Pennsylvania, United States, 16508

United States, South Carolina

Theravance Biopharma Investigational Site

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

Sponsors and Collaborators

Mylan Inc.

Theravance Biopharma

Investigators

• Study Director: Medical Monitor; Theravance Biopharma

  Study Documents (Full-Text)

Documents provided by Viatris Inc. ( Mylan Inc. ):

Study Protocol  [PDF] April 16, 2018

Statistical Analysis Plan  [PDF] October 1, 2018

More Information

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT03573817
• Other Study ID Numbers: 0167
• First Posted: June 29, 2018
• Results First Posted: December 18, 2019
• Last Update Posted: February 24, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Viatris Inc. ( Mylan Inc. ):

Chronic Obstructive Pulmonary Disease; Pulmonary Function; COPD; Performist

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Formoterol Fumarate; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action