Revefenacin Peak Inspiratory Flow Rate (PIFR) Study in COPD

• Sponsor: Mylan Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03095456
• Collaborator: Theravance Biopharma (Industry)
• Enrollment: 207
• Location: 1
• Arms: 2
• Actual Duration (Months): 8
• Patients Per Site Per Month: 25.9

Study Details

Study Description

Brief Summary

This study is a randomized, double-blind, double-dummy, parallel group study to compare once daily nebulized Revefenacin with Spiriva once daily delivered via the HandiHaler® on lung function in subjects with COPD and a Low Peak Inspiratory Flow Rate.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease, COPD; Low Peak Inspiratory Flow Rate (PIFR)	Drug: Revefenacin; Combination Product: Spiriva Handihaler®; Drug: Placebo for Revefenacin; Drug: Placebo for Spiriva Handihaler®	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 207 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3b, Randomized, Double-Blind, Double-Dummy, Parallel-Group, Study to Compare Once Daily Nebulized Revefenacin With Spiriva Once Daily Delivered Via the HandiHaler® on Lung Function in Subjects With COPD and a Low PIFR
• Actual Study Start Date: Mar 27, 2017
• Actual Primary Completion Date: Nov 25, 2017
• Actual Study Completion Date: Nov 25, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Revefenacin Active Revefenacin and placebo (in place of Spiriva Handihaler®)	Drug: Revefenacin; Revefenacin administered via nebulization.; Other Names: TD-4208 ; Drug: Placebo for Spiriva Handihaler®; Placebo administered as double blind, double dummy via Spiriva HandiHaler®.
Active Comparator: Spiriva Handihaler® Active Spiriva Handihaler® and placebo (in place of Revefenacin)	Combination Product: Spiriva Handihaler®; Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device.; Other Names: Tiotropium ; Drug: Placebo for Revefenacin; Placebo administered as double blind, double dummy via nebulization.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Trough FEV1 on Day 29 [Baseline and Day 29]

   FEV1 = forced expiratory volume at one second

Secondary Outcome Measures

1. Change From Baseline Trough FVC (Forced Vital Capacity) on Day 29 [Baseline and Day 29]

2. Change From Baseline Trough Inspiratory Capacity (IC) on Day 29 [Baseline and Day 29]

3. Change From Baseline Peak FEV1 on Day 29 [Baseline and Day 29 (0-4 hours)]

4. Change From Baseline Peak FVC on Day 29 [Baseline and Day 29 (0-4 hours)]

5. Summary of Rescue Medication Use: Puffs Per Day [1 Month]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is a male or female subject 40 years of age or older with a diagnosis of COPD.

• Subject has a current or past cigarette smoking history (or equivalent for cigar or pipe smoking history) of at least 10 pack-years.

• Subject is willing and able to provide signed and dated written informed consent to participate prior to initiation of any study related procedures.

Exclusion Criteria:

• Subject has a concurrent disease or condition that, in the opinion of the investigator, would interfere with continued study participation or confound the evaluation of safety and tolerability of the study drug.

• Subject has a history of reactions or hypersensitivity to inhaled or nebulized anticholinergics.

• Subject 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research of Rock Hill	Rock Hill	South Carolina	United States	29732

Sponsors and Collaborators

• Mylan Inc.
• Theravance Biopharma

Investigators

• Study Director: Medical Monitor, Theravance Biopharma

Study Documents (Full-Text)

• Study Protocol - Apr 4, 2017
• Statistical Analysis Plan - Nov 27, 2017

More Information

Publications

None provided.

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT03095456
• Other Study ID Numbers: 0149
• First Posted: Mar 29, 2017
• Last Update Posted: Feb 24, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mylan Inc.: Chronic Obstructive Pulmonary Disease, COPD; Low Peak Inspiratory Flow Rate (PIFR)
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration; Tiotropium Bromide

Study Results

Participant Flow

Arm/Group Title	Revefenacin	Spiriva Handihaler®
Arm/Group Description	Active Revefenacin and placebo (in place of Spiriva Handihaler®) Revefenacin: Revefenacin administered via nebulization. Placebo for Spiriva Handihaler®: Placebo administered as double blind, double dummy via Spiriva HandiHaler®.	Active Spiriva Handihaler® and placebo (in place of Revefenacin) Spiriva Handihaler®: Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
Period Title: Overall Study
STARTED	103	104
COMPLETED	99	96
NOT COMPLETED	4	8

Baseline Characteristics

Arm/Group Title	Revefenacin	Spiriva Handihaler®	Total
Arm/Group Description	Active Revefenacin and placebo (in place of Spiriva Handihaler®) Revefenacin: Revefenacin administered via nebulization. Placebo for Spiriva Handihaler®: Placebo administered as double blind, double dummy via Spiriva HandiHaler®.	Active Spiriva Handihaler® and placebo (in place of Revefenacin) Spiriva Handihaler®: Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.	Total of all reporting groups
Overall Participants	102	104	206
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	51 50%	53 51%	104 50.5%
>=65 years	51 50%	51 49%	102 49.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.1 (7.94)	65.1 (8.36)	65.1 (8.13)
Sex: Female, Male (Count of Participants)
Female	42 41.2%	40 38.5%	82 39.8%
Male	60 58.8%	64 61.5%	124 60.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 4.9%	3 2.9%	8 3.9%
Not Hispanic or Latino	96 94.1%	101 97.1%	197 95.6%
Unknown or Not Reported	1 1%	0 0%	1 0.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	12 11.8%	9 8.7%	21 10.2%
White	90 88.2%	95 91.3%	185 89.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	102 100%	104 100%	206 100%
Smoking history (Count of Participants)
Current Smoker	46 45.1%	50 48.1%	96 46.6%
Former Smoker	56 54.9%	54 51.9%	110 53.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Trough FEV1 on Day 29
Description	FEV1 = forced expiratory volume at one second
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) analysis set

Arm/Group Title	Revefenacin	Spiriva Handihaler®
Arm/Group Description	Active Revefenacin and placebo (in place of Spiriva Handihaler®) Revefenacin: Revefenacin administered via nebulization. Placebo for Spiriva Handihaler®: Placebo administered as double blind, double dummy via Spiriva HandiHaler®.	Active Spiriva Handihaler® and placebo (in place of Revefenacin) Spiriva Handihaler®: Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
Measure Participants	89	90
Least Squares Mean (Standard Error) [mL]	63.0 (20.17)	47.3 (19.06)

2. Secondary Outcome

Title	Change From Baseline Trough FVC (Forced Vital Capacity) on Day 29
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Revefenacin	Spiriva Handihaler®
Arm/Group Description	Active Revefenacin and placebo (in place of Spiriva Handihaler®) Revefenacin: Revefenacin administered via nebulization. Placebo for Spiriva Handihaler®: Placebo administered as double blind, double dummy via Spiriva HandiHaler®.	Active Spiriva Handihaler® and placebo (in place of Revefenacin) Spiriva Handihaler®: Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
Measure Participants	89	90
Least Squares Mean (Standard Error) [mL]	125.4 (38.75)	55.8 (36.62)

3. Secondary Outcome

Title	Change From Baseline Trough Inspiratory Capacity (IC) on Day 29
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Revefenacin	Spiriva Handihaler®
Arm/Group Description	Active Revefenacin and placebo (in place of Spiriva Handihaler®) Revefenacin: Revefenacin administered via nebulization. Placebo for Spiriva Handihaler®: Placebo administered as double blind, double dummy via Spiriva HandiHaler®.	Active Spiriva Handihaler® and placebo (in place of Revefenacin) Spiriva Handihaler®: Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
Measure Participants	82	88
Least Squares Mean (Standard Error) [mL]	71.4 (42.33)	84.1 (40.02)

4. Secondary Outcome

Title	Change From Baseline Peak FEV1 on Day 29
Time Frame	Baseline and Day 29 (0-4 hours)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Revefenacin	Spiriva Handihaler®
Arm/Group Description	Active Revefenacin and placebo (in place of Spiriva Handihaler®) Revefenacin: Revefenacin administered via nebulization. Placebo for Spiriva Handihaler®: Placebo administered as double blind, double dummy via Spiriva HandiHaler®.	Active Spiriva Handihaler® and placebo (in place of Revefenacin) Spiriva Handihaler®: Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
Measure Participants	91	90
Least Squares Mean (Standard Error) [mL]	174.2 (18.70)	197.7 (17.73)

5. Secondary Outcome

Title	Change From Baseline Peak FVC on Day 29
Time Frame	Baseline and Day 29 (0-4 hours)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Revefenacin	Spiriva Handihaler®
Arm/Group Description	Active Revefenacin and placebo (in place of Spiriva Handihaler®) Revefenacin: Revefenacin administered via nebulization. Placebo for Spiriva Handihaler®: Placebo administered as double blind, double dummy via Spiriva HandiHaler®.	Active Spiriva Handihaler® and placebo (in place of Revefenacin) Spiriva Handihaler®: Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
Measure Participants	91	90
Least Squares Mean (Standard Error) [mL]	354.2 (37.35)	340.1 (35.49)

6. Secondary Outcome

Title	Summary of Rescue Medication Use: Puffs Per Day
Time Frame	1 Month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Revefenacin	Spiriva Handihaler®
Arm/Group Description	Active Revefenacin and placebo (in place of Spiriva Handihaler®) Revefenacin: Revefenacin administered via nebulization. Placebo for Spiriva Handihaler®: Placebo administered as double blind, double dummy via Spiriva HandiHaler®.	Active Spiriva Handihaler® and placebo (in place of Revefenacin) Spiriva Handihaler®: Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
Measure Participants	101	95
Least Squares Mean (Standard Error) [puffs per day]	3.4 (0.42)	2.9 (0.41)

Adverse Events

Time Frame	From signing of ICF through the final follow-up assessment (approximately 1 month).
Arm/Group Title	Revefenacin		Spiriva Handihaler®
Arm/Group Description	Active Revefenacin and placebo (in place of Spiriva Handihaler®) Revefenacin: Revefenacin administered via nebulization. Placebo for Spiriva Handihaler®: Placebo administered as double blind, double dummy via Spiriva HandiHaler®.		Active Spiriva Handihaler® and placebo (in place of Revefenacin) Spiriva Handihaler®: Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device. Placebo for Revefenacin: Placebo administered as double blind, double dummy via nebulization.
All Cause Mortality
	Revefenacin		Spiriva Handihaler®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/103 (0%)		0/104 (0%)
Serious Adverse Events
	Revefenacin		Spiriva Handihaler®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/103 (0%)		1/104 (1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/103 (0%)	0	1/104 (1%)	1
Other (Not Including Serious) Adverse Events
	Revefenacin		Spiriva Handihaler®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/103 (4.9%)		21/104 (20.2%)
Gastrointestinal disorders
Constipation	0/103 (0%)	0	4/104 (3.8%)	4
Dry Mouth	2/103 (1.9%)	2	1/104 (1%)	1
Infections and infestations
Upper respiratory tract infection	0/103 (0%)	0	3/104 (2.9%)	3
Nervous system disorders
Headache	1/103 (1%)	1	5/104 (4.8%)	5
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/103 (1%)	1	4/104 (3.8%)	4
Oropharyngeal pain	2/103 (1.9%)	2	3/104 (2.9%)	3
Cough	0/103 (0%)	0	4/104 (3.8%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PI may communicate the trial results generated by the PI, but only after the first publication or presentation of the combined study results generated by all participating sites. The Sponsor can then review trial results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The Sponsor cannot require changes to the communication and cannot extend the embargo.