Trial Outcomes & Findings for Efficacy Study of Nebulized TD-4208 for Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02459080)

NCT ID: NCT02459080

Last Updated: 2022-02-24

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

619 participants

Primary outcome timeframe

Day 85

Results posted on

2022-02-24

Participant Flow

Participant milestones

Participant milestones
Measure	TD-4208-1 88 mcg TD-4208	TD-4208-2 175 mcg TD-4208	Placebo Placebo Placebo
Overall Study STARTED	212	198	209
Overall Study COMPLETED	168	158	151
Overall Study NOT COMPLETED	44	40	58

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TD-4208-1 n=212 Participants 88 mcg TD-4208	TD-4208-2 n=198 Participants 175 mcg TD-4208	Placebo n=209 Participants Placebo Placebo	Total n=619 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	112 Participants n=5 Participants	96 Participants n=7 Participants	104 Participants n=5 Participants	312 Participants n=4 Participants
Age, Categorical >=65 years	100 Participants n=5 Participants	102 Participants n=7 Participants	105 Participants n=5 Participants	307 Participants n=4 Participants
Age, Continuous	63.7 years STANDARD_DEVIATION 8.90 • n=5 Participants	64.2 years STANDARD_DEVIATION 8.60 • n=7 Participants	64.3 years STANDARD_DEVIATION 9.12 • n=5 Participants	64.1 years STANDARD_DEVIATION 8.87 • n=4 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	105 Participants n=7 Participants	100 Participants n=5 Participants	302 Participants n=4 Participants
Sex: Female, Male Male	115 Participants n=5 Participants	93 Participants n=7 Participants	109 Participants n=5 Participants	317 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	205 Participants n=5 Participants	186 Participants n=7 Participants	204 Participants n=5 Participants	595 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants	16 Participants n=7 Participants	17 Participants n=5 Participants	49 Participants n=4 Participants
Race (NIH/OMB) White	194 Participants n=5 Participants	179 Participants n=7 Participants	191 Participants n=5 Participants	564 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	212 participants n=5 Participants	198 participants n=7 Participants	209 participants n=5 Participants	619 participants n=4 Participants
Smoking Status Current Smoker	102 Participants n=5 Participants	96 Participants n=7 Participants	103 Participants n=5 Participants	301 Participants n=4 Participants
Smoking Status Former Smoker	110 Participants n=5 Participants	102 Participants n=7 Participants	106 Participants n=5 Participants	318 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 85

Population: Intent-to-treat (ITT) analysis set

Outcome measures

Outcome measures
Measure	TD-4208-1 n=161 Participants 88 mcg TD-4208	TD-4208-2 n=156 Participants 175 mcg TD-4208	Placebo n=146 Participants Placebo Placebo
Change From Baseline in Trough FEV1 on Day 85	59.81 mL Standard Error 15.095	126.85 mL Standard Error 15.389	-19.41 mL Standard Error 16.108

SECONDARY outcome

Timeframe: Days 15 to 85

Outcome measures

Outcome measures
Measure	TD-4208-1 n=201 Participants 88 mcg TD-4208	TD-4208-2 n=189 Participants 175 mcg TD-4208	Placebo n=191 Participants Placebo Placebo
Summary of Trough FEV1 Overall Treatment Effect From Day 15 to Day 85	73.0 mL Standard Error 3.10	124.8 mL Standard Error 3.20	-30.8 mL Standard Error 3.18

SECONDARY outcome

Timeframe: 0-2 hours after First Dose Day 1

Outcome measures

Outcome measures
Measure	TD-4208-1 n=212 Participants 88 mcg TD-4208	TD-4208-2 n=198 Participants 175 mcg TD-4208	Placebo n=208 Participants Placebo Placebo
Summary of Change From Baseline to Peak FEV1 After First Dose	218.14 mL Standard Error 9.546	224.46 mL Standard Error 9.744	91.79 mL Standard Error 9.963

SECONDARY outcome

Timeframe: 1-3 Months

Outcome measures

Outcome measures
Measure	TD-4208-1 n=212 Participants 88 mcg TD-4208	TD-4208-2 n=197 Participants 175 mcg TD-4208	Placebo n=206 Participants Placebo Placebo
Summary of Rescue Medication Use: Puffs Per Day	2.26 Puffs per Day Standard Error 0.234	2.27 Puffs per Day Standard Error 0.239	2.72 Puffs per Day Standard Error 0.246

SECONDARY outcome

Timeframe: 1-3 Months

Outcome measures

Outcome measures
Measure	TD-4208-1 n=211 Participants 88 mcg TD-4208	TD-4208-2 n=197 Participants 175 mcg TD-4208	Placebo n=209 Participants Placebo Placebo
Percentage of Albuterol Rescue-free 24-hour Periods	48.35 Percentage of 24 hr periods Standard Error 2.784	43.57 Percentage of 24 hr periods Standard Error 2.829	45.21 Percentage of 24 hr periods Standard Error 2.890

SECONDARY outcome

Timeframe: Baseline to Day 85

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

Outcome measures

Outcome measures
Measure	TD-4208-1 n=148 Participants 88 mcg TD-4208	TD-4208-2 n=139 Participants 175 mcg TD-4208	Placebo n=136 Participants Placebo Placebo
St. George's Respiratory Questionnaire (SGRQ) Proportion of Responders on Day 85	70 Participants	68 Participants	46 Participants

Adverse Events

TD-4208-1

Serious events: 10 serious events

Other events: 51 other events

Deaths: 0 deaths

TD-4208-2

Serious events: 10 serious events

Other events: 46 other events

Deaths: 0 deaths

Placebo

Serious events: 14 serious events

Other events: 51 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	TD-4208-1 n=212 participants at risk 88 mcg TD-4208	TD-4208-2 n=198 participants at risk 175 mcg TD-4208	Placebo n=209 participants at risk Placebo Placebo
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	8.0% 17/212 • Number of events 17 • From signing of ICF through the final follow-up assessment, Day 85.	10.6% 21/198 • Number of events 21 • From signing of ICF through the final follow-up assessment, Day 85.	11.0% 23/209 • Number of events 23 • From signing of ICF through the final follow-up assessment, Day 85.
Respiratory, thoracic and mediastinal disorders Cough	3.8% 8/212 • Number of events 8 • From signing of ICF through the final follow-up assessment, Day 85.	3.5% 7/198 • Number of events 7 • From signing of ICF through the final follow-up assessment, Day 85.	3.8% 8/209 • Number of events 8 • From signing of ICF through the final follow-up assessment, Day 85.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.3% 7/212 • Number of events 7 • From signing of ICF through the final follow-up assessment, Day 85.	2.0% 4/198 • Number of events 4 • From signing of ICF through the final follow-up assessment, Day 85.	5.3% 11/209 • Number of events 11 • From signing of ICF through the final follow-up assessment, Day 85.
Nervous system disorders Headache	3.3% 7/212 • Number of events 7 • From signing of ICF through the final follow-up assessment, Day 85.	4.0% 8/198 • Number of events 8 • From signing of ICF through the final follow-up assessment, Day 85.	2.4% 5/209 • Number of events 5 • From signing of ICF through the final follow-up assessment, Day 85.
Infections and infestations Upper respiratory tract infection	6.6% 14/212 • Number of events 14 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	1.9% 4/209 • Number of events 4 • From signing of ICF through the final follow-up assessment, Day 85.
Infections and infestations Nasopharyngitis	3.3% 7/212 • Number of events 7 • From signing of ICF through the final follow-up assessment, Day 85.	3.0% 6/198 • Number of events 6 • From signing of ICF through the final follow-up assessment, Day 85.	2.4% 5/209 • Number of events 5 • From signing of ICF through the final follow-up assessment, Day 85.
Infections and infestations Sinusitis	1.4% 3/212 • Number of events 3 • From signing of ICF through the final follow-up assessment, Day 85.	2.5% 5/198 • Number of events 5 • From signing of ICF through the final follow-up assessment, Day 85.	2.9% 6/209 • Number of events 6 • From signing of ICF through the final follow-up assessment, Day 85.

Additional Information

Head of Clinical Development & Medical Affairs

Theravance Biopharma

Phone: 1-855-633-8479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	TD-4208-1 n=212 participants at risk 88 mcg TD-4208	TD-4208-2 n=198 participants at risk 175 mcg TD-4208	Placebo n=209 participants at risk Placebo Placebo
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.47% 1/212 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Gastrointestinal disorders Gastric volvulus	0.47% 1/212 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Gastrointestinal disorders Ileus	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Infections and infestations Cellulitis	0.47% 1/212 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Infections and infestations Pneumonia parainfluenzae viral	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.47% 1/212 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Nervous system disorders Dizziness	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Nervous system disorders Migraine	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Nervous system disorders Transient ischaemic attack	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Ear and labyrinth disorders Vertigo	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Injury, poisoning and procedural complications Femur fracture	0.47% 1/212 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Psychiatric disorders Panic attack	0.47% 1/212 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Vascular disorders Superior vena cava syndrome	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
General disorders Chest pain	0.47% 1/212 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
General disorders Non-cardiac chest pain	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
General disorders Chest discomfort	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
General disorders Death	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Cardiac disorders Acute myocardial infarction	0.47% 1/212 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Cardiac disorders Atrial fibrillation	0.47% 1/212 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Cardiac disorders Congestive cardiomyopathy	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Cardiac disorders Silent myocardial infarction	0.47% 1/212 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	2.0% 4/198 • Number of events 4 • From signing of ICF through the final follow-up assessment, Day 85.	0.96% 2/209 • Number of events 2 • From signing of ICF through the final follow-up assessment, Day 85.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/198 • From signing of ICF through the final follow-up assessment, Day 85.	0.48% 1/209 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/212 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/198 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/209 • From signing of ICF through the final follow-up assessment, Day 85.