Clinical trial NCT05165485: Phase 4 COPD and Suboptimal Inspiratory Flow Rate
Official title: A Phase 4, Randomized, Double-Blind, Double-Dummy, Parallel-Group, Study Comparing Improvements in Lung Function in Adults With Severe to Very Severe Chronic Obstructive Pulmonary Disease and Suboptimal Inspiratory Flow Rate Following Once-Daily Treatment Over 12 Weeks With Either Revefenacin Inhalation Solution Delivered Via Standard Jet Nebulizer or Tiotropium Delivered Via a Dry Powder Inhaler (Spiriva® HandiHaler®)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Peak Inspiratory Flow Rate
PIFR
Pulmonary Function
Lead sponsor: Theravance Biopharma
Sponsor class: INDUSTRY
Collaborators: name: Viatris Inc.
First posted: 2021-12-21
Enrollment: 404
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study is a randomized, double-blind, double-dummy, parallel-group study evaluating efficacy and safety of revefenacin vs. tiotropium in adults with severe to very severe COPD and suboptimal PIFR.


Eligibility criteria: Inclusion Criteria:

1. Participant is a male or female 40 years of age or older.
2. Participant is female and is nonpregnant and nonlactating. A woman of childbearing potential must have a documented negative urine pregnancy test at screening. Women are considered not to be of childbearing potential if they have had a total hysterectomy and/or bilateral tubal ligation (documentation for either must be provided before enrollment) or are at least 2 years postmenopausal.
3. During the study and for 30 days after receiving the last dose of study drug, women of childbearing potential and men capable of fathering children must agree to use highly effective birth control measures or agree to abstain from sexual intercourse.

   A highly effective method of birth control is defined as one that results in a low failure rate (i.e. \<1% per year) when used consistently and correctly, such as condom + diaphragm, condom + spermicide, diaphragm + spermicide, or intrauterine device \[IUD\] with documented failure rate of \<1% per year, or oral/injectable/implanted hormonal contraceptives used in combination with an additional barrier method.
4. Participant has a diagnosis of COPD, specifically, a post-ipratropium FEV1/FVC ratio \<0.7.
5. Participant has a post ipratropium 30% ≤ FEV1 \< 50% of predicted normal (using National Health and Nutrition Examination Survey-predicted equations) and absolute FEV1 \> 500 mL, or FEV1 \<30% predicted normal and absolute FEV1 \> 700 mL.
6. Participant has a PIFR \<60 L/min as measured by an In-Check™ device with resistance set to DISKUS at Visit 1A (if not combined with Visit 1B) and \< 55 L/min as measured by an In-Check™ device with resistance set to DISKUS at Visit 1B and Visit 2 prior to randomization.
7. Participant is capable of performing reproducible spirometry maneuvers (and plethysmography maneuvers for a subset of participants) as described by current American Thoracic Society (ATS) Guidelines.
8. Participant is an active or former smoker with a cigarette smoking history (or equivalent for cigar or pipe smoking history) of at least 10 pack-years.
9. Participant or legal guardian is willing and able to provide signed and dated informed consent to participate prior to initiation of any study related procedures.
10. Participant is willing and able to adhere to all study assessments/procedures. Care partner assistance is acceptable.
11. Participant is willing and able to adhere to all restrictions during their study participation as follows:

    * Use of recreational drugs
    * Medicinal marijuana
    * Excessive alcohol during the study period
    * Participation in another investigational drug study
    * Donation of ≥500 mL blood (or equivalent)
12. Participant (or care partner) based on the investigator's assessment is able to properly prepare and administer study medication administered from both nebulizer and HandiHaler® according to their respective Instructions for Use.

Exclusion Criteria:

1. 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 and tolerability of the study drug.
2. Participant has a history of reactions or hypersensitivity to inhaled or nebulized anticholinergics.
3. Participant 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.
4. Participant has Moderate to Severe Hepatic impairment (Child-Pugh B or C) or Severe Renal Insufficiency (i.e. a glomerular filtration rate \<30 mL/min/1.72m\^2).
5. Participant has been hospitalized for COPD or pneumonia within 8 weeks prior to Visit 1.
6. Participant is receiving a LABA or LABA/inhaled corticosteroid (ICS; either QD or BID) at a dose that has been stable for ≤ 30 days prior to screening.
7. Participant has used systemic corticosteroids within 8 weeks of Visit 1.
8. Participant has used antibiotics for respiratory tract infections within 8 weeks of Visit 1, or is using antibiotics prophylactically.
9. Participant received COVID-19 vaccine within 2 weeks prior to Visit 1.

Primary outcomes:
measure: FEV1
timeFrame: Baseline, Day 85 following 84 days of dosing
Secondary outcomes:
measure: OTE on FEV1
timeFrame: Baseline, Day 30, Day 60, Day 85
measure: FEV1
timeFrame: Baseline, Day 30
measure: FEV1
timeFrame: Baseline, Day 60
measure: FVC
timeFrame: Baseline, Day 85
measure: 80-mL Increase in FEV1 at Trough on Day 85
timeFrame: Baseline, Day 85
measure: First Occurrence of CompEx Event
timeFrame: Date of first dose through date of last dose + 7 days
Other outcomes:
Locations:
city: Jasper
country: United States
facility: Theravance Biopharma Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: Theravance Biopharma Investigational Site
state: Arizona
city: Tucson
country: United States
facility: Theravance Biopharma Investigational Site
state: Arizona
city: Newport Beach
country: United States
facility: Theravance Biopharma Investigational Site
state: California
city: San Diego
country: United States
facility: Theravance Biopharma Investigational Site
state: California
city: Stockton
country: United States
facility: Theravance Biopharma Investigational Site
state: California
city: Upland
country: United States
facility: Theravance Biopharma Investigational Site
state: California
city: Lakewood
country: United States
facility: Theravance Biopharma Investigational Site
state: Colorado
city: Brandon
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Clearwater
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Clearwater
country: United States
facility: Theravance Biopharma Investigational Site site 2
state: Florida
city: Clearwater
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Daytona Beach
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Leesburg
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Miami
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Miami
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Orlando
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Ormond Beach
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Sarasota
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Tampa
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Winter Park
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Chicago Ridge
country: United States
facility: Theravance Biopharma Investigational Site
state: Illinois
city: River Forest
country: United States
facility: Theravance Biopharma Investigational Site
state: Illinois
city: Hammond
country: United States
facility: Theravance Biopharma Investigational Site
state: Indiana
city: Valparaiso
country: United States
facility: Theravance Biopharma Investigational Site
state: Indiana
city: Annapolis
country: United States
facility: Theravance Biopharma Investigational Site
state: Maryland
city: Columbia
country: United States
facility: Theravance Biopharma Investigational Site
state: Maryland
city: Oxon Hill
country: United States
facility: Theravance Biopharma Investigational Site
state: Maryland
city: Towson
country: United States
facility: Theravance Biopharma Investigational Site
state: Maryland
city: North Dartmouth
country: United States
facility: Theravance Biopharma Investigational Site
state: Massachusetts
city: Farmington Hills
country: United States
facility: Theravance Biopharma Investigational Site
state: Michigan
city: Saint Charles
country: United States
facility: Theravance Biopharma Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: Theravance Biopharma Investigational Site
state: Missouri
city: Missoula
country: United States
facility: Theravance Biopharma Investigational Site
state: Montana
city: Las Vegas
country: United States
facility: Theravance Biopharma Investigational Site
state: Nevada
city: Albuquerque
country: United States
facility: Theravance Biopharma Investigational Site
state: New Mexico
city: Bronxville
country: United States
facility: Theravance Biopharma Investigational Site
state: New York
city: Schenectady
country: United States
facility: Theravance Biopharma Investigational Site
state: New York
city: Charlotte
country: United States
facility: Theravance Biopharma Investigational Site
state: North Carolina
city: Hickory
country: United States
facility: Theravance Biopharma Investigational Site
state: North Carolina
city: Huntersville
country: United States
facility: Theravance Biopharma Investigational Site
state: North Carolina
city: Kernersville
country: United States
facility: Theravance Biopharma Investigational Site
state: North Carolina
city: Monroe
country: United States
facility: Theravance Biopharma Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: Theravance Biopharma Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Theravance Biopharma Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Theravance Biopharma Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Theravance Biopharma Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Theravance Biopharma Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Theravance Biopharma Investigational Site
state: Ohio
city: Marion
country: United States
facility: Theravance Biopharma Investigational Site
state: Ohio
city: Grants Pass
country: United States
facility: Theravance Biopharma Investigational Site
state: Oregon
city: Medford
country: United States
facility: Theravance Biopharma Investigational Site
state: Oregon
city: Portland
country: United States
facility: Theravance Biopharma Investigational Site
state: Oregon
city: Anderson
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: Columbia
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: Gaffney
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: Lexington
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: North Charleston
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: Rock Hill
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: Theravance Biopharma Investigational Site #2
state: South Carolina
city: Spartanburg
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: Union
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: Franklin
country: United States
facility: Theravance Biopharma Investigational Site
state: Tennessee
city: Johnson City
country: United States
facility: Theravance Biopharma Investigational Site
state: Tennessee
city: Knoxville
country: United States
facility: Theravance Biopharma Investigational Site
state: Tennessee
city: Kerrville
country: United States
facility: Theravance Biopharma Investigational Site
state: Texas
city: McAllen
country: United States
facility: Theravance Biopharma Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Theravance Biopharma Investigational Site
state: Texas
city: Sherman
country: United States
facility: Theravance Biopharma Investigational Site
state: Texas
city: Webster
country: United States
facility: Theravance Biopharma Investigational Site
state: Texas
city: Roy
country: United States
facility: Theravance Biopharma Investigational Site
state: Utah
city: West Valley City
country: United States
facility: Theravance Biopharma Investigational Site
state: Utah
city: Abingdon
country: United States
facility: Theravance Biopharma Investigational Site
state: Virginia
city: Spokane
country: United States
facility: Theravance Biopharma Investigational Site
state: Washington
city: Cudahy
country: United States
facility: Theravance Biopharma Investigational Site
state: Wisconsin
Study officials:
affiliation: Theravance Biopharma
name: Medical Monitor
role: STUDY_DIRECTOR
References: