Phase 4 COPD and Suboptimal Inspiratory Flow Rate

Phase 4

Completed

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: Revefenacin; Drug: Tiotropium; Drug: Revefenacin Placebo; Drug: Tiotropium Placebo

• Registration Number: NCT05165485
• Lead Sponsor: Theravance Biopharma

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-12-07
• Study First Submitted QC: 2021-12-07
• Study First Posted: 2021-12-21
• Study Start: 2022-01-07
• Primary Completion: 2023-11-13
• Study Completion: 2023-11-20
• Status Verified: 2024-11
• Results First Submitted: 2024-11-13
• Results First Submitted QC: 2024-12-17
• Last Update Submitted: 2024-12-17
• Results First Posted: 2024-12-20
• Last Update Posted: 2024-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 404

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tiotropium	Revefenacin Placebo	Tiotropium administered with Revefenacin Placebo
Revefenacin	Tiotropium Placebo	Revefenacin administered with Tiotropium Placebo
Revefenacin	Revefenacin	Revefenacin administered with Tiotropium Placebo
Tiotropium	Tiotropium	Tiotropium administered with Revefenacin Placebo

Primary Outcome Measures

Name	Time	Method
FEV1	Baseline, Day 85 following 84 days of dosing	Change from baseline in forced expiratory volume in one second (FEV1) at trough on Day 85

Secondary Outcome Measures

Name	Time	Method
OTE on FEV1	Baseline, Day 30, Day 60, Day 85	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.
FEV1	Baseline, Day 60	Change from baseline in FEV1 at trough on Day 60
FVC	Baseline, Day 85	Change from baseline in forced vital capacity (FVC) at trough on Day 85
80-mL Increase in FEV1 at Trough on Day 85	Baseline, 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.
First Occurrence of CompEx Event	Date of first dose through date of last dose + 7 days	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.

Trial Locations

Locations (3)

Theravance Biopharma Investigational Site site 2; 🇺🇸 Clearwater, Florida, United States

Theravance Biopharma Investigational Site; 🇺🇸 Cudahy, Wisconsin, United States

Theravance Biopharma Investigational Site #2; 🇺🇸 Spartanburg, South Carolina, United States