Efficacy Study of Nebulized TD-4208 for Chronic Obstructive Pulmonary Disease (COPD)

• Sponsor: Mylan Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02512510
• Collaborator: Theravance Biopharma (Industry)
• Enrollment: 611
• Location: 1
• Arms: 3
• Duration (Months): 12
• Patients Per Site Per Month: 50.8

Study Details

Study Description

Brief Summary

The purpose of this study is to measure the effectiveness and safety of TD 4208, an investigational drug being developed to treat people with moderate to very severe COPD, compared to placebo, a treatment without activity.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: TD-4208; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 611 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, 12-week, Randomized, Double-blind Placebo-controlled Parallel Group Study of Nebulized TD-4208 in Subjects With Chronic Obstructive Pulmonary Disease
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: TD-4208-1 88 mcg	Drug: TD-4208; Other Names: revefenacin
Active Comparator: TD-4208-2 175 mcg	Drug: TD-4208; Other Names: revefenacin
Placebo Comparator: Placebo Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Trough FEV1 on Day 85 [Baseline and Day 85]

Secondary Outcome Measures

1. Summary of Trough FEV1 Overall Treatment Effect From Day 15 to Day 85 [Days 15 to 85]

2. Summary of Change From Baseline to Peak FEV1 After First Dose [0-2 hours after First Dose Day 1]

3. Summary of Rescue Medication Use: Puffs Per Day [1-3 Months]

4. St. George's Respiratory Questionnaire (SGRQ) Proportion of Responders on Day 85 [Day 85]

   A Responder is defined as someone who experienced a decrease in SGRQ score of 4 or more units

5. Percentage of Albuterol Rescue-free 24-hour Periods [1-3 Months]

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

Exclusion Criteria:

• Females who are pregnant, lactating, breast-feeding or planning to become pregnant during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Palmetto Medical Research Associates L.L.C.	Easley	South Carolina	United States	29640

Sponsors and Collaborators

• Mylan Inc.
• Theravance Biopharma

Investigators

• Study Director: Medical Monitor, Theravance Biopharma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT02512510
• Other Study ID Numbers: 0127
• First Posted: Jul 31, 2015
• Last Update Posted: Feb 24, 2022
• Last Verified: Feb 1, 2022

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

Study Results

Participant Flow

Arm/Group Title	TD-4208-1	TD-4208-2	Placebo
Arm/Group Description	88 mcg TD-4208	175 mcg TD-4208	Placebo Placebo
Period Title: Overall Study
STARTED	205	197	209
COMPLETED	163	162	157
NOT COMPLETED	42	35	52

Baseline Characteristics

Arm/Group Title	TD-4208-1	TD-4208-2	Placebo	Total
Arm/Group Description	88 mcg TD-4208	175 mcg TD-4208	Placebo Placebo	Total of all reporting groups
Overall Participants	205	197	208	610
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	121 59%	106 53.8%	115 55.3%	342 56.1%
>=65 years	84 41%	91 46.2%	93 44.7%	268 43.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.1 (8.81)	63.6 (9.19)	63.5 (8.91)	63.4 (8.95)
Sex: Female, Male (Count of Participants)
Female	102 49.8%	95 48.2%	111 53.4%	308 50.5%
Male	103 50.2%	102 51.8%	97 46.6%	302 49.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	17 8.3%	10 5.1%	12 5.8%	39 6.4%
Not Hispanic or Latino	188 91.7%	186 94.4%	194 93.3%	568 93.1%
Unknown or Not Reported	0 0%	1 0.5%	2 1%	3 0.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.5%	0 0%	1 0.2%
Asian	1 0.5%	2 1%	0 0%	3 0.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	17 8.3%	21 10.7%	20 9.6%	58 9.5%
White	186 90.7%	171 86.8%	188 90.4%	545 89.3%
More than one race	1 0.5%	2 1%	0 0%	3 0.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	205 100%	197 100%	208 100%	610 100%
Smoking Status (Count of Participants)
Current Smoker	97 47.3%	94 47.7%	95 45.7%	286 46.9%
Former Smoker	108 52.7%	103 52.3%	113 54.3%	324 53.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Trough FEV1 on Day 85
Time Frame	Baseline and Day 85

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) analysis set

Arm/Group Title	TD-4208-1	TD-4208-2	Placebo
Arm/Group Description	88 mcg TD-4208	175 mcg TD-4208	Placebo Placebo
Measure Participants	152	154	150
Least Squares Mean (Standard Error) [mL]	115.58 (18.637)	102.90 (18.542)	-44.92 (18.841)

2. Secondary Outcome

Title	Summary of Trough FEV1 Overall Treatment Effect From Day 15 to Day 85
Time Frame	Days 15 to 85

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TD-4208-1	TD-4208-2	Placebo
Arm/Group Description	88 mcg TD-4208	175 mcg TD-4208	Placebo Placebo
Measure Participants	189	181	187
Mean (Standard Error) [mL]	83.9 (3.14)	87.1 (3.21)	-39.9 (3.15)

3. Secondary Outcome

Title	Summary of Change From Baseline to Peak FEV1 After First Dose
Time Frame	0-2 hours after First Dose Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TD-4208-1	TD-4208-2	Placebo
Arm/Group Description	88 mcg TD-4208	175 mcg TD-4208	Placebo Placebo
Measure Participants	204	196	208
Least Squares Mean (Standard Error) [mL]	218.65 (10.291)	216.84 (10.248)	88.22 (10.092)

4. Secondary Outcome

Title	Summary of Rescue Medication Use: Puffs Per Day
Time Frame	1-3 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TD-4208-1	TD-4208-2	Placebo
Arm/Group Description	88 mcg TD-4208	175 mcg TD-4208	Placebo Placebo
Measure Participants	202	196	203
Least Squares Mean (Standard Error) [Puffs per Day]	2.00 (0.207)	2.38 (0.204)	2.54 (0.206)

5. Secondary Outcome

Title	St. George's Respiratory Questionnaire (SGRQ) Proportion of Responders on Day 85
Description	A Responder is defined as someone who experienced a decrease in SGRQ score of 4 or more units
Time Frame	Day 85

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TD-4208-1	TD-4208-2	Placebo
Arm/Group Description	88 mcg TD-4208	175 mcg TD-4208	Placebo Placebo
Measure Participants	145	149	140
Count of Participants [Participants]	67 32.7%	67 34%	54 26%

6. Secondary Outcome

Title	Percentage of Albuterol Rescue-free 24-hour Periods
Time Frame	1-3 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TD-4208-1	TD-4208-2	Placebo
Arm/Group Description	88 mcg TD-4208	175 mcg TD-4208	Placebo Placebo
Measure Participants	205	197	207
Least Squares Mean (Standard Error) [Percentage of 24hr periods]	44.79 (2.800)	43.26 (2.769)	37.23 (2.766)

Adverse Events

Time Frame	From signing of ICF through the final follow-up assessment, Day 85.
Arm/Group Title	TD-4208-1		TD-4208-2		Placebo
Arm/Group Description	88 mcg TD-4208		175 mcg TD-4208		Placebo Placebo
All Cause Mortality
	TD-4208-1		TD-4208-2		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/205 (0%)		1/197 (0.5%)		0/209 (0%)
Serious Adverse Events
	TD-4208-1		TD-4208-2		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/205 (5.4%)		5/197 (2.5%)		7/209 (3.3%)
Gastrointestinal disorders
Small intestinal obstruction	1/205 (0.5%)	1	0/197 (0%)	0	0/209 (0%)	0
General disorders
Chest pain	1/205 (0.5%)	1	0/197 (0%)	0	0/209 (0%)	0
Infections and infestations
Cellulitis	1/205 (0.5%)	1	0/197 (0%)	0	1/209 (0.5%)	1
Bronchitis	0/205 (0%)	0	1/197 (0.5%)	1	0/209 (0%)	0
Bronchitis bacterial	1/205 (0.5%)	1	0/197 (0%)	0	0/209 (0%)	0
Pneumonia	0/205 (0%)	0	1/197 (0.5%)	1	0/209 (0%)	0
Metabolism and nutrition disorders
Lactic acidosis	1/205 (0.5%)	1	0/197 (0%)	0	0/209 (0%)	0
Musculoskeletal and connective tissue disorders
Bursitis	0/205 (0%)	0	0/197 (0%)	0	1/209 (0.5%)	1
Musculoskeletal Chest Pain	0/205 (0%)	0	1/197 (0.5%)	1	0/209 (0%)	0
Nervous system disorders
Cerebrolvascular Accident	0/205 (0%)	0	0/197 (0%)	0	1/209 (0.5%)	1
Spondylitic myelopathy	0/205 (0%)	0	0/197 (0%)	0	1/209 (0.5%)	1
Psychiatric disorders
Bipolar disorder	0/205 (0%)	0	1/197 (0.5%)	1	0/209 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	8/205 (3.9%)	8	1/197 (0.5%)	1	4/209 (1.9%)	4
Acute respiratory failure	2/205 (1%)	2	0/197 (0%)	0	0/209 (0%)	0
Respiratory Failure	1/205 (0.5%)	1	0/197 (0%)	0	0/209 (0%)	0
Social circumstances
Victim of homicide	0/205 (0%)	0	1/197 (0.5%)	1	0/209 (0%)	0
Other (Not Including Serious) Adverse Events
	TD-4208-1		TD-4208-2		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/205 (28.8%)		62/197 (31.5%)		52/209 (24.9%)
Infections and infestations
Upper respiratory tract infection	6/205 (2.9%)	6	10/197 (5.1%)	10	5/209 (2.4%)	5
Nasopharyngitis	7/205 (3.4%)	7	9/197 (4.6%)	9	4/209 (1.9%)	4
Musculoskeletal and connective tissue disorders
Back Pain	4/205 (2%)	4	7/197 (3.6%)	7	3/209 (1.4%)	3
Nervous system disorders
Headache	14/205 (6.8%)	14	8/197 (4.1%)	8	6/209 (2.9%)	6
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	25/205 (12.2%)	25	21/197 (10.7%)	21	25/209 (12%)	25
Cough	9/205 (4.4%)	9	10/197 (5.1%)	10	9/209 (4.3%)	9
Dyspnoea	6/205 (2.9%)	6	8/197 (4.1%)	8	12/209 (5.7%)	12

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.