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

• Sponsor: Mylan Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02459080
• Collaborator: Theravance Biopharma (Industry)
• Enrollment: 619
• Location: 1
• Arms: 3
• Duration (Months): 12
• Patients Per Site Per Month: 51.5

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

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

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

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	Allergy Associates Research Center (AARC)	Portland	Oregon	United States	97202

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: NCT02459080
• Other Study ID Numbers: 0126
• First Posted: Jun 1, 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	212	198	209
COMPLETED	168	158	151
NOT COMPLETED	44	40	58

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	212	198	209	619
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	112 52.8%	96 48.5%	104 49.8%	312 50.4%
>=65 years	100 47.2%	102 51.5%	105 50.2%	307 49.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.7 (8.90)	64.2 (8.60)	64.3 (9.12)	64.1 (8.87)
Sex: Female, Male (Count of Participants)
Female	97 45.8%	105 53%	100 47.8%	302 48.8%
Male	115 54.2%	93 47%	109 52.2%	317 51.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 1.9%	6 3%	3 1.4%	13 2.1%
Not Hispanic or Latino	205 96.7%	186 93.9%	204 97.6%	595 96.1%
Unknown or Not Reported	3 1.4%	6 3%	2 1%	11 1.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
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	16 7.5%	16 8.1%	17 8.1%	49 7.9%
White	194 91.5%	179 90.4%	191 91.4%	564 91.1%
More than one race	1 0.5%	1 0.5%	1 0.5%	3 0.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	212 100%	198 100%	209 100%	619 100%
Smoking Status (Count of Participants)
Current Smoker	102 48.1%	96 48.5%	103 49.3%	301 48.6%
Former Smoker	110 51.9%	102 51.5%	106 50.7%	318 51.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Trough FEV1 on Day 85
Time Frame	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	161	156	146
Least Squares Mean (Standard Error) [mL]	59.81 (15.095)	126.85 (15.389)	-19.41 (16.108)

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	201	189	191
Mean (Standard Error) [mL]	73.0 (3.10)	124.8 (3.20)	-30.8 (3.18)

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	212	198	208
Least Squares Mean (Standard Error) [mL]	218.14 (9.546)	224.46 (9.744)	91.79 (9.963)

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	212	197	206
Least Squares Mean (Standard Error) [Puffs per Day]	2.26 (0.234)	2.27 (0.239)	2.72 (0.246)

5. 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	211	197	209
Least Squares Mean (Standard Error) [Percentage of 24 hr periods]	48.35 (2.784)	43.57 (2.829)	45.21 (2.890)

6. 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	Baseline to 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	148	139	136
Count of Participants [Participants]	70 33%	68 34.3%	46 22%

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	0/212 (0%)		0/198 (0%)		1/209 (0.5%)
Serious Adverse Events
	TD-4208-1		TD-4208-2		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/212 (4.7%)		10/198 (5.1%)		14/209 (6.7%)
Cardiac disorders
Acute myocardial infarction	1/212 (0.5%)	1	1/198 (0.5%)	1	0/209 (0%)	0
Atrial fibrillation	1/212 (0.5%)	1	0/198 (0%)	0	0/209 (0%)	0
Congestive cardiomyopathy	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Silent myocardial infarction	1/212 (0.5%)	1	0/198 (0%)	0	0/209 (0%)	0
Ear and labyrinth disorders
Vertigo	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Gastrointestinal disorders
Upper gastrointestinal haemorrhage	1/212 (0.5%)	1	1/198 (0.5%)	1	0/209 (0%)	0
Abdominal discomfort	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Gastric volvulus	1/212 (0.5%)	1	0/198 (0%)	0	0/209 (0%)	0
Ileus	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
General disorders
Chest pain	1/212 (0.5%)	1	1/198 (0.5%)	1	0/209 (0%)	0
Non-cardiac chest pain	0/212 (0%)	0	1/198 (0.5%)	1	1/209 (0.5%)	1
Chest discomfort	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Death	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Infections and infestations
Cellulitis	1/212 (0.5%)	1	0/198 (0%)	0	0/209 (0%)	0
Pneumonia parainfluenzae viral	0/212 (0%)	0	1/198 (0.5%)	1	0/209 (0%)	0
Injury, poisoning and procedural complications
Femur fracture	1/212 (0.5%)	1	0/198 (0%)	0	0/209 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Rheumatoid arthritis	1/212 (0.5%)	1	0/198 (0%)	0	0/209 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	0/212 (0%)	0	1/198 (0.5%)	1	0/209 (0%)	0
Invasive ductal breast carcinoma	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Lung adenocarcinoma	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Squamous cell carcinoma	0/212 (0%)	0	1/198 (0.5%)	1	0/209 (0%)	0
Nervous system disorders
Dizziness	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Migraine	0/212 (0%)	0	1/198 (0.5%)	1	0/209 (0%)	0
Transient ischaemic attack	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Psychiatric disorders
Panic attack	1/212 (0.5%)	1	0/198 (0%)	0	0/209 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/212 (0%)	0	4/198 (2%)	4	2/209 (1%)	2
Bronchiectasis	0/212 (0%)	0	1/198 (0.5%)	1	0/209 (0%)	0
Dyspnoea	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Hypoxia	0/212 (0%)	0	1/198 (0.5%)	1	0/209 (0%)	0
Pneumothorax spontaneous	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Respiratory failure	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
Vascular disorders
Superior vena cava syndrome	0/212 (0%)	0	0/198 (0%)	0	1/209 (0.5%)	1
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	51/212 (24.1%)		46/198 (23.2%)		51/209 (24.4%)
Infections and infestations
Upper respiratory tract infection	14/212 (6.6%)	14	1/198 (0.5%)	1	4/209 (1.9%)	4
Nasopharyngitis	7/212 (3.3%)	7	6/198 (3%)	6	5/209 (2.4%)	5
Sinusitis	3/212 (1.4%)	3	5/198 (2.5%)	5	6/209 (2.9%)	6
Nervous system disorders
Headache	7/212 (3.3%)	7	8/198 (4%)	8	5/209 (2.4%)	5
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	17/212 (8%)	17	21/198 (10.6%)	21	23/209 (11%)	23
Cough	8/212 (3.8%)	8	7/198 (3.5%)	7	8/209 (3.8%)	8
Dyspnoea	7/212 (3.3%)	7	4/198 (2%)	4	11/209 (5.3%)	11

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.