A 28-Day Parallel Group Study of TD-4208 in Chronic Obstructive Pulmonary Disease (COPD)

• Sponsor: Mylan Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02040792
• Collaborator: Theravance Biopharma (Industry)
• Enrollment: 355
• Location: 1
• Arms: 5
• Duration (Months): 3
• Patients Per Site Per Month: 117.4

Study Details

Study Description

Brief Summary

This study evaluated the safety and efficacy of four doses of TD-4208 and a placebo product when administered once daily for 28 days using a jet nebulizer to patients with moderate to severe chronic obstructive pulmonary disease.

Condition or Disease	Intervention/Treatment	Phase
COPD	Drug: TD-4208; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 355 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2B, 28-Day, Randomized, Double-Blind Placebo-Controlled Parallel Group Study of Nebulized TD-4208 in Subjects With Chronic Obstructive Pulmonary Disease
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo	Drug: Placebo
Experimental: 44 mcg TD-4208	Drug: TD-4208; Other Names: revefenacin
Experimental: 88 mcg TD-4208	Drug: TD-4208; Other Names: revefenacin
Experimental: 175 mcg TD-4208	Drug: TD-4208; Other Names: revefenacin
Experimental: 350 mcg TD-4208	Drug: TD-4208; Other Names: revefenacin

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Trough FEV1 (Forced Expiratory Volume in One Second) [Baseline to 28 days]

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

• Subject must have a negative pregnancy test, and must be prepared to use effective contraception if of child-bearing potential

• Subject is capable of performing reproducible spirometry maneuvers

• Subject has post-bronchodilator FEV1/FVC ratio <0.7

• Subject has moderate-to-severe stable COPD (Stage 2 or 3 according to the GOLD Guidelines)

• Subject has a post-bronchodilator FEV1 greater than or equal to 30% and less than 80% of predicted normal

• Subject has a current or past smoking history of at least 10 pack-years.

Exclusion Criteria:

• Subject has a significant respiratory disease or disorder other than COPD that would affect the interpretation of data from this study

• Subject has a history of reactions or hypersensitivity to inhaled or nebulized anticholinergic or beta-agonist agents

• Subject suffers from any medical condition that would preclude the use of inhaled anticholinergic agents

• Subject has been hospitalized for COPD or pneumonia within 12 weeks

• Subject requires long-term oxygen therapy (>15 hours a day)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Upstate Pharmaceutical Research	Greenville	South Carolina	United States	29615

Sponsors and Collaborators

• Mylan Inc.
• Theravance Biopharma

Investigators

• Study Director: Medial Monitor, Theravance Biopharma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT02040792
• Other Study ID Numbers: 0117
• First Posted: Jan 20, 2014
• Last Update Posted: Feb 24, 2022
• Last Verified: Feb 1, 2022

• Keywords provided by Mylan Inc.: COPD; Chronic Obstructive Pulmonary Disease
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Pre-assignment Detail	One subject who received placebo was excluded from the efficacy analysis. The reason for this is that the subject was found to be participating in a GSK (GlaxoSmithKline) study with another investigational agent at the same time as their participation in this study.

Arm/Group Title	Placebo	44 mcg	88 mcg	175 mcg	350 mcg
Arm/Group Description	Placebo Placebo	TD-4208 TD-4208	TD-4208 TD-4208	TD-4208 TD-4208	TD-4208 TD-4208
Period Title: Overall Study
STARTED	70	68	71	71	74
COMPLETED	64	65	68	64	67
NOT COMPLETED	6	3	3	7	7

Baseline Characteristics

Arm/Group Title	Placebo	44 mcg	88 mcg	175 mcg	350 mcg	Total
Arm/Group Description	Placebo Placebo	TD-4208 TD-4208	TD-4208 TD-4208	TD-4208 TD-4208	TD-4208 TD-4208	Total of all reporting groups
Overall Participants	70	68	71	71	74	354
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.2 (9.17)	60.9 (8.87)	60.4 (7.98)	64.5 (7.69)	61.4 (8.98)	61.9 (8.63)
Sex: Female, Male (Count of Participants)
Female	33 47.1%	36 52.9%	39 54.9%	34 47.9%	34 45.9%	176 49.7%
Male	37 52.9%	32 47.1%	32 45.1%	37 52.1%	40 54.1%	178 50.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Trough FEV1 (Forced Expiratory Volume in One Second)
Time Frame	Baseline to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	44 mcg	88 mcg	175 mcg	350 mcg
Arm/Group Description	Placebo Placebo	TD-4208 TD-4208	TD-4208 TD-4208	TD-4208 TD-4208	TD-4208 TD-4208
Measure Participants	70	68	71	71	74
Least Squares Mean (Standard Error) [mL]	-32.4 (25.36)	19.4 (24.98)	155.0 (24.61)	134.2 (25.07)	138.2 (24.38)

Adverse Events

Adverse Event Reporting Description	One subject who received placebo was excluded from the efficacy analysis. The reason for this is that the subject was found to be participating in a GSK study with another investigational agent at the same time as their participation in this study.
Arm/Group Title	Placebo		44 mcg		88 mcg		175 mcg		350 mcg
Arm/Group Description	Placebo Placebo		TD-4208 TD-4208		TD-4208 TD-4208		TD-4208 TD-4208		TD-4208 TD-4208
All Cause Mortality
	Placebo		44 mcg		88 mcg		175 mcg		350 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		44 mcg		88 mcg		175 mcg		350 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/71 (0%)		1/68 (1.5%)		0/71 (0%)		2/71 (2.8%)		1/74 (1.4%)
Cardiac disorders
Supraventricular tachycardia	0/71 (0%)	0	1/68 (1.5%)	1	0/71 (0%)	0	0/71 (0%)	0	0/74 (0%)	0
Angina Unstable	0/71 (0%)	0	0/68 (0%)	0	0/71 (0%)	0	1/71 (1.4%)	1	0/74 (0%)	0
Gastrointestinal disorders
Intestinal Obstruction	0/71 (0%)	0	0/68 (0%)	0	0/71 (0%)	0	0/71 (0%)	0	1/74 (1.4%)	1
Vascular disorders
Hypertension	0/71 (0%)	0	0/68 (0%)	0	0/71 (0%)	0	1/71 (1.4%)	1	0/74 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		44 mcg		88 mcg		175 mcg		350 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/71 (11.3%)		1/68 (1.5%)		6/71 (8.5%)		10/71 (14.1%)		15/74 (20.3%)
General disorders
Headache	2/71 (2.8%)	2	1/68 (1.5%)	1	2/71 (2.8%)	2	1/71 (1.4%)	1	5/74 (6.8%)	5
Oropharyngeal pain	1/71 (1.4%)	1	1/68 (1.5%)	1	0/71 (0%)	0	0/71 (0%)	0	2/74 (2.7%)	2
Musculoskeletal and connective tissue disorders
Back pain	0/71 (0%)	0	0/68 (0%)	0	1/71 (1.4%)	1	2/71 (2.8%)	2	1/74 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/71 (2.8%)	2	0/68 (0%)	0	3/71 (4.2%)	3	3/71 (4.2%)	3	2/74 (2.7%)	2
Cough	1/71 (1.4%)	1	0/68 (0%)	0	0/71 (0%)	0	3/71 (4.2%)	3	3/74 (4.1%)	3
COPD	2/71 (2.8%)	2	0/68 (0%)	0	0/71 (0%)	0	1/71 (1.4%)	1	2/74 (2.7%)	2

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.