CClinicalTrials.gg
CompletedNCT05165485PIFR-2Updated Dec 20, 2024Results posted

Phase 4 COPD and Suboptimal Inspiratory Flow Rate

A Phase 4 interventional study of Revefenacin and Tiotropium in Chronic Obstructive Pulmonary Disease, sponsored by Theravance Biopharma. Completed at 76 sites in United States. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2024-12-20.

Sponsored by Theravance Biopharma · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
404
Allocation
Randomized
Ages
40 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Chronic Obstructive Pulmonary Disease

Keywords

  • COPD
  • Peak Inspiratory Flow Rate
  • PIFR
  • Pulmonary Function
03

In context

Lung Diseases

3,303 studies on the registry are indexed under Lung Diseases; 355 are open to participants now.

This study's enrollment of 404 is above the median of 72 across 2,118 interventional studies indexed under Lung Diseases.

Browse Lung Diseases studies →

Lead sponsor

Theravance Biopharma is the lead sponsor of 47 studies on the registry; none are open to participants now.

Of its 24 completed or terminated interventional studies of FDA-regulated products, 11 (46%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
404 participants (actual)

Study arms

  • Experimental
    Revefenacin

    Revefenacin administered with Tiotropium Placebo

    Drug: Revefenacin · Drug: Tiotropium Placebo

  • Active comparator
    Tiotropium

    Tiotropium administered with Revefenacin Placebo

    Drug: Tiotropium · Drug: Revefenacin Placebo

Interventions

  • DrugRevefenacin

    Revefenacin 175 mcg administered once daily for 84 days via nebulization

    Also known as: Yupelri®, TD-4208

  • DrugTiotropium

    Tiotropium 18 mcg administered once daily for 84 days via Spiriva HandiHaler®

    Also known as: Spiriva®

  • DrugRevefenacin Placebo

    Placebo for Revefenacin administered once daily for 84 days via nebulization

  • DrugTiotropium Placebo

    Placebo for Tiotropium administered once daily for 84 days via Spiriva HandiHaler®

06

What researchers measure

Primary outcomes

  1. FEV1

    Change from baseline in forced expiratory volume in one second (FEV1) at trough on Day 85

    Time frame: Baseline, Day 85 following 84 days of dosing

Secondary outcomes

  1. OTE on FEV1

    Trough Overall Treatment Effect (OTE) on FEV1. Overall is defined as the average change from baseline at trough across Day 30, Day 60, and Day 85.

    Time frame: Baseline, Day 30, Day 60, Day 85

  2. FEV1

    Change from baseline in FEV1 at trough on Day 30

    Time frame: Baseline, Day 30

  3. FEV1

    Change from baseline in FEV1 at trough on Day 60

    Time frame: Baseline, Day 60

  4. FVC

    Change from baseline in forced vital capacity (FVC) at trough on Day 85

    Time frame: Baseline, Day 85

  5. 80-mL Increase in FEV1 at Trough on Day 85

    Participants with an 80-mL or greater change from baseline FEV1 at trough were counted as responders. Participants with change from baseline FEV1 \< 80 mL and participants with change from baseline FEV1 not obtained were counted as nonresponders.

    Time frame: Baseline, Day 85

  6. First Occurrence of CompEx Event

    Count of participants experiencing events and time from first dose to first occurrence of a composite endpoint for exacerbations of COPD (CompEx) event were evaluated. The statistical analysis is a Cox proportional hazards model analysis of time to first event and the Revefenacin / Tiotropium hazard ratio is calculated and reported. Data are reported as the numbers of subjects with events and the hazard ratio is included in the Statistical Analysis section attached to the Outcome Measure data table. CompEx events are a composite of moderate or severe COPD exacerbation, premature termination from the study for any reason other than Sponsor decision, and clinically relevant deterioration in COPD. Clinically relevant deterioration events are defined as increases in COPD symptoms meeting specified criteria based on participant diary data.

    Time frame: Date of first dose through date of last dose + 7 days

07

Results

Posted Dec 20, 2024

Participant flow

Participant flow — Overall Study
MilestoneTiotropiumRevefenacin
Started191190
Completed156147
Not completed3543

Outcome measures

PrimaryFEV1

Change from baseline in forced expiratory volume in one second (FEV1) at trough on Day 85

Time frame:
Baseline, Day 85 following 84 days of dosing
Reported as:
Least squares mean · mL
FEV1
mLTiotropiumRevefenacin
FEV1101 ± 1778 ± 17
Statistical analysis
  • Tiotropium vs Revefenacin · Mixed Models Analysis · p = 0.22 (The familywise type 1 error rate is controlled at 0.05 by testing the primary and secondary endpoint hypotheses in sequence, stopping after the first failure to reject the null hypothesis.) · Mean difference (net): -23 · 95% CI -61 to 14Revefenacin - Tiotropium Least Squares Mean Difference
SecondaryOTE on FEV1

Trough Overall Treatment Effect (OTE) on FEV1. Overall is defined as the average change from baseline at trough across Day 30, Day 60, and Day 85.

Time frame:
Baseline, Day 30, Day 60, Day 85
Reported as:
Least squares mean · mL
OTE on FEV1
mLTiotropiumRevefenacin
OTE on FEV187 ± 1578 ± 15
Statistical analysis
  • Tiotropium vs Revefenacin · Mixed Models Analysis · Mean difference (net): -9 · 95% CI -38 to 20Revefenacin - Tiotropium Least Squares Mean Difference
SecondaryFEV1

Change from baseline in FEV1 at trough on Day 30

Time frame:
Baseline, Day 30
Reported as:
Least squares mean · mL
FEV1
mLTiotropiumRevefenacin
FEV181 ± 1683 ± 16
Statistical analysis
  • Tiotropium vs Revefenacin · Mixed Models Analysis · Mean difference (net): 2 · 95% CI -29 to 32Revefenacin - Tiotropium Least Squares Mean Difference
SecondaryFEV1

Change from baseline in FEV1 at trough on Day 60

Time frame:
Baseline, Day 60
Reported as:
Least squares mean · mL
FEV1
mLTiotropiumRevefenacin
FEV179 ± 1773 ± 17
Statistical analysis
  • Tiotropium vs Revefenacin · Mixed Models Analysis · Mean difference (net): -6 · 95% CI -40 to 29Revefenacin - Tiotropium Least Squares Mean Difference
SecondaryFVC

Change from baseline in forced vital capacity (FVC) at trough on Day 85

Time frame:
Baseline, Day 85
Reported as:
Least squares mean · mL
FVC
mLTiotropiumRevefenacin
FVC198 ± 35156 ± 35
Statistical analysis
  • Tiotropium vs Revefenacin · Mixed Models Analysis · Mean difference (net): -41 · 95% CI -118 to 35Revefenacin - Tiotropium Least Squares Mean Difference.
Secondary80-mL Increase in FEV1 at Trough on Day 85

Participants with an 80-mL or greater change from baseline FEV1 at trough were counted as responders. Participants with change from baseline FEV1 \< 80 mL and participants with change from baseline FEV1 not obtained were counted as nonresponders.

Time frame:
Baseline, Day 85
Reported as:
Count of participants · Participants
80-mL Increase in FEV1 at Trough on Day 85
ParticipantsTiotropiumRevefenacin
80-mL Increase in FEV1 at Trough on Day 858363
Statistical analysis
  • Tiotropium vs Revefenacin · Regression, Logistic · Odds ratio (or): 0.60 · 95% CI 0.39 to 0.92The profile likelihood method was used to estimate the Revefenacin / Tiotropium responder OR.
SecondaryFirst Occurrence of CompEx Event

Count of participants experiencing events and time from first dose to first occurrence of a composite endpoint for exacerbations of COPD (CompEx) event were evaluated. The statistical analysis is a Cox proportional hazards model analysis of time to first event and the Revefenacin / Tiotropium hazard ratio is calculated and reported. Data are reported as the numbers of subjects with events and the hazard ratio is included in the Statistical Analysis section attached to the Outcome Measure data table. CompEx events are a composite of moderate or severe COPD exacerbation, premature termination from the study for any reason other than Sponsor decision, and clinically relevant deterioration in COPD. Clinically relevant deterioration events are defined as increases in COPD symptoms meeting specified criteria based on participant diary data.

Time frame:
Date of first dose through date of last dose + 7 days
Reported as:
Count of participants · Participants
First Occurrence of CompEx Event
ParticipantsTiotropiumRevefenacin
First Occurrence of CompEx Event5658
Statistical analysis
  • Tiotropium vs Revefenacin · Regression, Cox · Hazard ratio (hr): 1.00 · 95% CI 0.69 to 1.45The profile likelihood method was used to estimate the Revefenacin / Tiotropium HR.

Adverse events

Collected over Day 1 through 7 days after the date of the last study drug dose.. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Tiotropium0/191 (0%)15/191 (7.9%)33/191 (17.3%)
Revefenacin0/189 (0%)16/189 (8.5%)38/189 (20.1%)
Most frequent serious events
Showing 10 of 26
Most frequent serious events
EventTiotropiumRevefenacin
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders4/1914/189
Cardiac failure congestiveCardiac disorders0/1913/189
COVID-19Infections and infestations1/1912/189
PneumoniaInfections and infestations2/1912/189
Acute kidney injuryRenal and urinary disorders2/1911/189
Atrial fibrillationCardiac disorders0/1911/189
Cardiac arrestCardiac disorders0/1911/189
Chronic left ventricular failureCardiac disorders0/1911/189
ColitisGastrointestinal disorders0/1911/189
COVID-19 pneumoniaInfections and infestations0/1911/189
Most frequent other events
Most frequent other events
EventTiotropiumRevefenacin
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders22/19122/189
HeadacheNervous system disorders5/1912/189
Back painMusculoskeletal and connective tissue disorders2/1914/189
NauseaGastrointestinal disorders4/1912/189
COVID-19Infections and infestations1/1913/189
CellulitisInfections and infestations1/1913/189
NasopharyngitisInfections and infestations2/1913/189
Upper respiratory tract infectionInfections and infestations2/1913/189

Baseline characteristics

All participants who received study treatment

Age, Continuous
Age, Continuous(years)TiotropiumRevefenacinTotal
Median66 (49 to 88)67 (47 to 83)66 (47 to 88)
Age, Customized
Age, Customized(Participants)TiotropiumRevefenacinTotal
40 to 64 years old8179160
65 years old and over110110220
Sex: Female, Male
Sex: Female, Male(Participants)TiotropiumRevefenacinTotal
Female8690176
Male10599204
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)TiotropiumRevefenacinTotal
Hispanic or Latino279
Not Hispanic or Latino176172348
Unknown or Not Reported131023
Race (NIH/OMB)
Race (NIH/OMB)(Participants)TiotropiumRevefenacinTotal
American Indian or Alaska Native213
Asian112
Native Hawaiian or Other Pacific Islander011
Black or African American111425
White175171346
More than one race000
Unknown or Not Reported213
Region of Enrollment
Region of Enrollment(Participants)TiotropiumRevefenacinTotal
United States191189380
08

Study locations

76 sites
  • Theravance Biopharma Investigational Site
    Jasper, Alabama 35501, United States
  • Theravance Biopharma Investigational Site
    Phoenix, Arizona 85018, United States
  • Theravance Biopharma Investigational Site
    Tucson, Arizona 85715, United States
  • Theravance Biopharma Investigational Site
    Newport Beach, California 92663, United States
  • Theravance Biopharma Investigational Site
    San Diego, California 92120, United States
  • Theravance Biopharma Investigational Site
    Stockton, California 95207, United States
  • Theravance Biopharma Investigational Site
    Upland, California 91786, United States
  • Theravance Biopharma Investigational Site
    Lakewood, Colorado 80228, United States
  • Theravance Biopharma Investigational Site
    Brandon, Florida 33511, United States
  • Theravance Biopharma Investigational Site
    Clearwater, Florida 33756, United States
  • Theravance Biopharma Investigational Site site 2
    Clearwater, Florida 33765, United States
  • Theravance Biopharma Investigational Site
    Clearwater, Florida 33765, United States
  • Theravance Biopharma Investigational Site
    Daytona Beach, Florida 32117, United States
  • Theravance Biopharma Investigational Site
    Leesburg, Florida 34748, United States
  • Theravance Biopharma Investigational Site
    Miami, Florida 33155, United States
  • Theravance Biopharma Investigational Site
    Miami, Florida 33186, United States
  • Theravance Biopharma Investigational Site
    Orlando, Florida 32825, United States
  • Theravance Biopharma Investigational Site
    Ormond Beach, Florida 32174, United States
  • Theravance Biopharma Investigational Site
    Sarasota, Florida 34239, United States
  • Theravance Biopharma Investigational Site
    Tampa, Florida 33606, United States
  • Theravance Biopharma Investigational Site
    Winter Park, Florida 32789, United States
  • Theravance Biopharma Investigational Site
    Chicago Ridge, Illinois 60415, United States
  • Theravance Biopharma Investigational Site
    River Forest, Illinois 60305, United States
  • Theravance Biopharma Investigational Site
    Hammond, Indiana 46324, United States
  • Theravance Biopharma Investigational Site
    Valparaiso, Indiana 46383, United States
  • Theravance Biopharma Investigational Site
    Annapolis, Maryland 21401, United States
  • Theravance Biopharma Investigational Site
    Columbia, Maryland 21046, United States
  • Theravance Biopharma Investigational Site
    Oxon Hill, Maryland 20745, United States
  • Theravance Biopharma Investigational Site
    Towson, Maryland 21286, United States
  • Theravance Biopharma Investigational Site
    North Dartmouth, Massachusetts 02747, United States
  • Theravance Biopharma Investigational Site
    Farmington Hills, Michigan 48336, United States
  • Theravance Biopharma Investigational Site
    Saint Charles, Missouri 63301, United States
  • Theravance Biopharma Investigational Site
    Saint Louis, Missouri 63141, United States
  • Theravance Biopharma Investigational Site
    Missoula, Montana 59808, United States
  • Theravance Biopharma Investigational Site
    Las Vegas, Nevada 89106, United States
  • Theravance Biopharma Investigational Site
    Albuquerque, New Mexico 87108, United States
  • Theravance Biopharma Investigational Site
    Bronxville, New York 10708, United States
  • Theravance Biopharma Investigational Site
    Schenectady, New York 12308, United States
  • Theravance Biopharma Investigational Site
    Charlotte, North Carolina 28207, United States
  • Theravance Biopharma Investigational Site
    Hickory, North Carolina 28601, United States
  • Theravance Biopharma Investigational Site
    Huntersville, North Carolina 28078, United States
  • Theravance Biopharma Investigational Site
    Kernersville, North Carolina 27284, United States
  • Theravance Biopharma Investigational Site
    Monroe, North Carolina 28112, United States
  • Theravance Biopharma Investigational Site
    Raleigh, North Carolina 27607, United States
  • Theravance Biopharma Investigational Site
    Winston-Salem, North Carolina 27103, United States
  • Theravance Biopharma Investigational Site
    Cincinnati, Ohio 45236, United States
  • Theravance Biopharma Investigational Site
    Cincinnati, Ohio 45242, United States
  • Theravance Biopharma Investigational Site
    Columbus, Ohio 43215, United States
  • Theravance Biopharma Investigational Site
    Columbus, Ohio 43235, United States
  • Theravance Biopharma Investigational Site
    Marion, Ohio 43302, United States
  • Theravance Biopharma Investigational Site
    Grants Pass, Oregon 97527, United States
  • Theravance Biopharma Investigational Site
    Medford, Oregon 97504, United States
  • Theravance Biopharma Investigational Site
    Portland, Oregon 97202, United States
  • Theravance Biopharma Investigational Site
    Anderson, South Carolina 29621, United States
  • Theravance Biopharma Investigational Site
    Columbia, South Carolina 29204, United States
  • Theravance Biopharma Investigational Site
    Gaffney, South Carolina 29340, United States
  • Theravance Biopharma Investigational Site
    Greenville, South Carolina 29615, United States
  • Theravance Biopharma Investigational Site
    Lexington, South Carolina 29072, United States
  • Theravance Biopharma Investigational Site
    North Charleston, South Carolina 29406, United States
  • Theravance Biopharma Investigational Site
    Rock Hill, South Carolina 29732, United States
  • Theravance Biopharma Investigational Site #2
    Spartanburg, South Carolina 29303, United States
  • Theravance Biopharma Investigational Site
    Spartanburg, South Carolina 29303, United States
  • Theravance Biopharma Investigational Site
    Union, South Carolina 29379, United States
  • Theravance Biopharma Investigational Site
    Franklin, Tennessee 37067, United States
  • Theravance Biopharma Investigational Site
    Johnson City, Tennessee 37601, United States
  • Theravance Biopharma Investigational Site
    Knoxville, Tennessee 37909, United States
  • Theravance Biopharma Investigational Site
    Kerrville, Texas 78028, United States
  • Theravance Biopharma Investigational Site
    McAllen, Texas 78503, United States
  • Theravance Biopharma Investigational Site
    San Antonio, Texas 78229, United States
  • Theravance Biopharma Investigational Site
    Sherman, Texas 75092, United States
  • Theravance Biopharma Investigational Site
    Webster, Texas 77598, United States
  • Theravance Biopharma Investigational Site
    Roy, Utah 84067, United States
  • Theravance Biopharma Investigational Site
    West Valley City, Utah 84120, United States
  • Theravance Biopharma Investigational Site
    Abingdon, Virginia 24210, United States
  • Theravance Biopharma Investigational Site
    Spokane, Washington 99204, United States
  • Theravance Biopharma Investigational Site
    Cudahy, Wisconsin 53110, United States
09

References and documents

Study documents

  • Study protocol · Feb 27, 2023
  • Statistical analysis plan · Nov 10, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

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

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 20, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05165485
Lead sponsor
Theravance Biopharma
Collaborators
Viatris Inc.
Responsible party
Sponsor
First posted
Dec 21, 2021
Start date
Jan 7, 2022
Primary completion
Nov 13, 2023
Completion
Nov 20, 2023
Results posted
Dec 20, 2024
Last update
Dec 20, 2024

Study contacts

Medical Monitor
study director · Theravance Biopharma

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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