Trial Outcomes & Findings for Efficacy Study of Nebulized TD-4208 for Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02512510)

NCT ID: NCT02512510

Last Updated: 2022-02-24

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

611 participants

Primary outcome timeframe

Baseline and 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	205	197	209
Overall Study COMPLETED	163	162	157
Overall Study NOT COMPLETED	42	35	52

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=205 Participants 88 mcg TD-4208	TD-4208-2 n=197 Participants 175 mcg TD-4208	Placebo n=208 Participants Placebo Placebo	Total n=610 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	121 Participants n=5 Participants	106 Participants n=7 Participants	115 Participants n=5 Participants	342 Participants n=4 Participants
Age, Categorical >=65 years	84 Participants n=5 Participants	91 Participants n=7 Participants	93 Participants n=5 Participants	268 Participants n=4 Participants
Age, Continuous	63.1 years STANDARD_DEVIATION 8.81 • n=5 Participants	63.6 years STANDARD_DEVIATION 9.19 • n=7 Participants	63.5 years STANDARD_DEVIATION 8.91 • n=5 Participants	63.4 years STANDARD_DEVIATION 8.95 • n=4 Participants
Sex: Female, Male Female	102 Participants n=5 Participants	95 Participants n=7 Participants	111 Participants n=5 Participants	308 Participants n=4 Participants
Sex: Female, Male Male	103 Participants n=5 Participants	102 Participants n=7 Participants	97 Participants n=5 Participants	302 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	39 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	188 Participants n=5 Participants	186 Participants n=7 Participants	194 Participants n=5 Participants	568 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 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	17 Participants n=5 Participants	21 Participants n=7 Participants	20 Participants n=5 Participants	58 Participants n=4 Participants
Race (NIH/OMB) White	186 Participants n=5 Participants	171 Participants n=7 Participants	188 Participants n=5 Participants	545 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	0 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	205 participants n=5 Participants	197 participants n=7 Participants	208 participants n=5 Participants	610 participants n=4 Participants
Smoking Status Current Smoker	97 Participants n=5 Participants	94 Participants n=7 Participants	95 Participants n=5 Participants	286 Participants n=4 Participants
Smoking Status Former Smoker	108 Participants n=5 Participants	103 Participants n=7 Participants	113 Participants n=5 Participants	324 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Day 85

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

Outcome measures

Outcome measures
Measure	TD-4208-1 n=152 Participants 88 mcg TD-4208	TD-4208-2 n=154 Participants 175 mcg TD-4208	Placebo n=150 Participants Placebo Placebo
Change From Baseline in Trough FEV1 on Day 85	115.58 mL Standard Error 18.637	102.90 mL Standard Error 18.542	-44.92 mL Standard Error 18.841

SECONDARY outcome

Timeframe: Days 15 to 85

Outcome measures

Outcome measures
Measure	TD-4208-1 n=189 Participants 88 mcg TD-4208	TD-4208-2 n=181 Participants 175 mcg TD-4208	Placebo n=187 Participants Placebo Placebo
Summary of Trough FEV1 Overall Treatment Effect From Day 15 to Day 85	83.9 mL Standard Error 3.14	87.1 mL Standard Error 3.21	-39.9 mL Standard Error 3.15

SECONDARY outcome

Timeframe: 0-2 hours after First Dose Day 1

Outcome measures

Outcome measures
Measure	TD-4208-1 n=204 Participants 88 mcg TD-4208	TD-4208-2 n=196 Participants 175 mcg TD-4208	Placebo n=208 Participants Placebo Placebo
Summary of Change From Baseline to Peak FEV1 After First Dose	218.65 mL Standard Error 10.291	216.84 mL Standard Error 10.248	88.22 mL Standard Error 10.092

SECONDARY outcome

Timeframe: 1-3 Months

Outcome measures

Outcome measures
Measure	TD-4208-1 n=202 Participants 88 mcg TD-4208	TD-4208-2 n=196 Participants 175 mcg TD-4208	Placebo n=203 Participants Placebo Placebo
Summary of Rescue Medication Use: Puffs Per Day	2.00 Puffs per Day Standard Error 0.207	2.38 Puffs per Day Standard Error 0.204	2.54 Puffs per Day Standard Error 0.206

SECONDARY outcome

Timeframe: 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=145 Participants 88 mcg TD-4208	TD-4208-2 n=149 Participants 175 mcg TD-4208	Placebo n=140 Participants Placebo Placebo
St. George's Respiratory Questionnaire (SGRQ) Proportion of Responders on Day 85	67 Participants	67 Participants	54 Participants

SECONDARY outcome

Timeframe: 1-3 Months

Outcome measures

Outcome measures
Measure	TD-4208-1 n=205 Participants 88 mcg TD-4208	TD-4208-2 n=197 Participants 175 mcg TD-4208	Placebo n=207 Participants Placebo Placebo
Percentage of Albuterol Rescue-free 24-hour Periods	44.79 Percentage of 24hr periods Standard Error 2.800	43.26 Percentage of 24hr periods Standard Error 2.769	37.23 Percentage of 24hr periods Standard Error 2.766

Adverse Events

TD-4208-1

Serious events: 11 serious events

Other events: 59 other events

Deaths: 0 deaths

TD-4208-2

Serious events: 5 serious events

Other events: 62 other events

Deaths: 1 deaths

Placebo

Serious events: 7 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	TD-4208-1 n=205 participants at risk 88 mcg TD-4208	TD-4208-2 n=197 participants at risk 175 mcg TD-4208	Placebo n=209 participants at risk Placebo Placebo
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	12.2% 25/205 • Number of events 25 • From signing of ICF through the final follow-up assessment, Day 85.	10.7% 21/197 • Number of events 21 • From signing of ICF through the final follow-up assessment, Day 85.	12.0% 25/209 • Number of events 25 • From signing of ICF through the final follow-up assessment, Day 85.
Respiratory, thoracic and mediastinal disorders Cough	4.4% 9/205 • Number of events 9 • From signing of ICF through the final follow-up assessment, Day 85.	5.1% 10/197 • Number of events 10 • From signing of ICF through the final follow-up assessment, Day 85.	4.3% 9/209 • Number of events 9 • From signing of ICF through the final follow-up assessment, Day 85.
Nervous system disorders Headache	6.8% 14/205 • Number of events 14 • From signing of ICF through the final follow-up assessment, Day 85.	4.1% 8/197 • Number of events 8 • 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.9% 6/205 • Number of events 6 • From signing of ICF through the final follow-up assessment, Day 85.	4.1% 8/197 • Number of events 8 • From signing of ICF through the final follow-up assessment, Day 85.	5.7% 12/209 • Number of events 12 • From signing of ICF through the final follow-up assessment, Day 85.
Infections and infestations Upper respiratory tract infection	2.9% 6/205 • Number of events 6 • From signing of ICF through the final follow-up assessment, Day 85.	5.1% 10/197 • Number of events 10 • 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 Nasopharyngitis	3.4% 7/205 • Number of events 7 • From signing of ICF through the final follow-up assessment, Day 85.	4.6% 9/197 • Number of events 9 • 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.
Musculoskeletal and connective tissue disorders Back Pain	2.0% 4/205 • Number of events 4 • From signing of ICF through the final follow-up assessment, Day 85.	3.6% 7/197 • Number of events 7 • From signing of ICF through the final follow-up assessment, Day 85.	1.4% 3/209 • Number of events 3 • 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=205 participants at risk 88 mcg TD-4208	TD-4208-2 n=197 participants at risk 175 mcg TD-4208	Placebo n=209 participants at risk Placebo Placebo
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	3.9% 8/205 • Number of events 8 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/197 • 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.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.98% 2/205 • Number of events 2 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/197 • 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 Respiratory Failure	0.49% 1/205 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/197 • 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	0.49% 1/205 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/197 • 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.
Infections and infestations Bronchitis	0.00% 0/205 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/197 • 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 Bronchitis bacterial	0.49% 1/205 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/197 • 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	0.00% 0/205 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/197 • 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 Bursitis	0.00% 0/205 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/197 • 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 Musculoskeletal Chest Pain	0.00% 0/205 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/197 • 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 Cerebrolvascular Accident	0.00% 0/205 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/197 • 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 Spondylitic myelopathy	0.00% 0/205 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/197 • 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 Small intestinal obstruction	0.49% 1/205 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/197 • 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 Chest pain	0.49% 1/205 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/197 • 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.
Metabolism and nutrition disorders Lactic acidosis	0.49% 1/205 • Number of events 1 • From signing of ICF through the final follow-up assessment, Day 85.	0.00% 0/197 • 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 Bipolar disorder	0.00% 0/205 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/197 • 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.
Social circumstances Victim of homicide	0.00% 0/205 • From signing of ICF through the final follow-up assessment, Day 85.	0.51% 1/197 • 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.