Trial Outcomes & Findings for Effects of TD-4208 on FEV1 in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT03064113)
NCT ID: NCT03064113
Last Updated: 2022-02-24
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
32 participants
Primary outcome timeframe
From predose to 25 hours postdose
Results posted on
2022-02-24
Participant Flow
21-May-2011 (FPFV) through 07-Oct-2011 (LPLV)
Male and female subjects between the ages of 40 and 75 years-old with a clinical diagnosis of COPD and responsiveness to ipratropium bromide.
Participant milestones
| Measure |
Sequence 1
1. Intervention 1 (Placebo) - \[2 days\], washout \[7 days\],
2. Intervention 2 (TD4208 700 μg) - \[2 days\], washout \[7 days\],
3. Intervention 3 (TD-4208 350 μg) - \[2 days\], washout \[7 days\],
4. Intervention 4 (Ipratropium 500 μg) - \[2 days\], washout \[7 days\]
|
Sequence 2
1. Intervention 1 (TD-4208 700 μg) - \[2 days\], washout \[7 days\],
2. Intervention 2 (Ipratropium 500 μg) - \[2 days\], washout \[7 days\],
3. Intervention 3 (Placebo) - \[2 days\], washout \[7 days\],
4. Intervention 4 (TD-4208 350 μg) - \[2 days\], washout \[7 days\]
|
Sequence 3
1. Intervention 1 (TD-4208 350 μg) - \[2 days\], washout \[7 days\],
2. Intervention 2 (Placebo) - \[2 days\], washout \[7 days\],
3. Intervention 3 (Ipratropium 500 μg) - \[2 days\], washout \[7 days\],
4. Intervention 4 (TD-4208 700 μg) - \[2 days\], washout \[7 days\]
|
Sequence 4
1. Intervention 1(Ipratropium 500 μg) - \[2 days\], washout \[7 days\],
2. Intervention 2 (TD-4208 350 μg) - \[2 days\], washout \[7 days\],
3. Intervention 3 (TD-4208 700 μg) - \[2 days\], washout \[7 days\],
4. Intervention 4 (Placebo) - \[2 days\], washout \[7 days\]
|
|---|---|---|---|---|
|
Intervention 1 (2 Days)
STARTED
|
8
|
8
|
8
|
8
|
|
Intervention 1 (2 Days)
COMPLETED
|
8
|
8
|
8
|
8
|
|
Intervention 1 (2 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Washout (7 Days)
STARTED
|
8
|
8
|
8
|
8
|
|
Washout (7 Days)
COMPLETED
|
8
|
8
|
8
|
8
|
|
Washout (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Intervention 2 (2 Days)
STARTED
|
8
|
8
|
8
|
8
|
|
Intervention 2 (2 Days)
COMPLETED
|
8
|
8
|
8
|
8
|
|
Intervention 2 (2 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Intervention 3 (2 Days)
STARTED
|
8
|
8
|
8
|
8
|
|
Intervention 3 (2 Days)
COMPLETED
|
8
|
8
|
8
|
8
|
|
Intervention 3 (2 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Intervention 4 (2 Days)
STARTED
|
8
|
8
|
8
|
8
|
|
Intervention 4 (2 Days)
COMPLETED
|
8
|
8
|
8
|
8
|
|
Intervention 4 (2 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effects of TD-4208 on FEV1 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
Sequence 1
n=8 Participants
1. Intervention 1 (Placebo) - \[2 days\], washout \[7 days\],
2. Intervention 2 (TD-4208 700 μg) - \[2 days\], washout \[7 days\],
3. Intervention 3 (TD-4208 350 μg) - \[2 days\], washout \[7 days\],
4. Intervention 4 (Ipratropium 500 μg) - \[2 days\], washout \[7 days\]
|
Sequence 2
n=8 Participants
1. Intervention 1 (TD-4208 700 μg) - \[2 days\], washout \[7 days\],
2. Intervention 2 (Ipratropium 500 μg) - \[2 days\], washout \[7 days\],
3. Intervention 3 (Placebo) - \[2 days\], washout \[7 days\],
4. Intervention 4 (TD-4208 350 μg) - \[2 days\], washout \[7 days\]
|
Sequence 3
n=8 Participants
1. Intervention 1 (TD-4208 350 μg) - \[2 days\], washout \[7 days\],
2. Intervention 2 (Placebo) - \[2 days\], washout \[7 days\],
3. Intervention 3 (Ipratropium 500 μg) - \[2 days\], washout \[7 days\],
4. Intervention 4 (TD-4208 700 μg) - \[2 days\], washout \[7 days\]
|
Sequence 4
n=8 Participants
1. Intervention 1 (Ipratropium 500 μg) - \[2 days\], washout \[7 days\],
2. Intervention 2 (TD-4208 350 μg) - \[2 days\], washout \[7 days\],
3. Intervention 3 (TD-4208 700 μg) - \[2 days\], washout \[7 days\],
4. Intervention 4 (Placebo) - \[2 days\], washout \[7 days\]
|
Total
n=32 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
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Age, Continuous
|
60.25 years
STANDARD_DEVIATION 7.48 • n=5 Participants
|
63.25 years
STANDARD_DEVIATION 8.21 • n=7 Participants
|
59.63 years
STANDARD_DEVIATION 3.67 • n=5 Participants
|
64.88 years
STANDARD_DEVIATION 7.75 • n=4 Participants
|
62.00 years
STANDARD_DEVIATION 6.78 • n=21 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Region of Enrollment
New Zealand
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
4 participants
n=5 Participants
|
4 participants
n=4 Participants
|
16 participants
n=21 Participants
|
|
Region of Enrollment
South Africa
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
4 participants
n=5 Participants
|
4 participants
n=4 Participants
|
16 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: From predose to 25 hours postdoseOutcome measures
| Measure |
Placebo
n=32 Participants
Single dose of placebo administered via nebulizer
|
TD-4208 700 μg
n=32 Participants
Single dose of TD-4208 700 μg administered via nebulizer
|
TD-4208 350 μg
n=32 Participants
Single dose of TD-4208 350 μg administered via nebulizer
|
Ipratropium 500 μg
n=32 Participants
Single dose of Ipratropium 500 μg administered via nebulizer
|
|---|---|---|---|---|
|
Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline
|
1708.0 mL
Standard Error 32.7
|
1877.3 mL
Standard Error 32.7
|
1881.8 mL
Standard Error 32.7
|
1883.6 mL
Standard Error 32.8
|
SECONDARY outcome
Timeframe: 12 hr and 24 hrOutcome measures
| Measure |
Placebo
n=32 Participants
Single dose of placebo administered via nebulizer
|
TD-4208 700 μg
n=32 Participants
Single dose of TD-4208 700 μg administered via nebulizer
|
TD-4208 350 μg
n=32 Participants
Single dose of TD-4208 350 μg administered via nebulizer
|
Ipratropium 500 μg
n=32 Participants
Single dose of Ipratropium 500 μg administered via nebulizer
|
|---|---|---|---|---|
|
Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo
FEV1 at 12hr
|
1519.2 mL
Standard Error 30.9
|
1642.6 mL
Standard Error 31.4
|
1631.7 mL
Standard Error 30.9
|
1534.5 mL
Standard Error 31.4
|
|
Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo
FEV1 at 24 hr
|
1533.8 mL
Standard Error 22.4
|
1670.4 mL
Standard Error 22.4
|
1636.6 mL
Standard Error 22.4
|
1509.6 mL
Standard Error 22.4
|
SECONDARY outcome
Timeframe: 12 hr and 24 hrOutcome measures
| Measure |
Placebo
n=32 Participants
Single dose of placebo administered via nebulizer
|
TD-4208 700 μg
n=32 Participants
Single dose of TD-4208 700 μg administered via nebulizer
|
TD-4208 350 μg
n=32 Participants
Single dose of TD-4208 350 μg administered via nebulizer
|
Ipratropium 500 μg
n=32 Participants
Single dose of Ipratropium 500 μg administered via nebulizer
|
|---|---|---|---|---|
|
Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo
AUC 0-12 hrs
|
262.1 hr*mL
Standard Error 4.2
|
291.2 hr*mL
Standard Error 4.2
|
288.5 hr*mL
Standard Error 4.2
|
287.7 hr*mL
Standard Error 4.2
|
|
Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo
AUC 0-24 hrs
|
261.2 hr*mL
Standard Error 4.0
|
286.6 hr*mL
Standard Error 4.0
|
281.3 hr*mL
Standard Error 4.1
|
271.7 hr*mL
Standard Error 4.0
|
SECONDARY outcome
Timeframe: 12hr and 24hrOutcome measures
| Measure |
Placebo
n=32 Participants
Single dose of placebo administered via nebulizer
|
TD-4208 700 μg
n=32 Participants
Single dose of TD-4208 700 μg administered via nebulizer
|
TD-4208 350 μg
n=32 Participants
Single dose of TD-4208 350 μg administered via nebulizer
|
Ipratropium 500 μg
n=32 Participants
Single dose of Ipratropium 500 μg administered via nebulizer
|
|---|---|---|---|---|
|
Peak Expiratory Flow Rate (PEFR) From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1
Peak FEF 25-75% 24hr
|
0.8 L/sec
Standard Error 0.0
|
0.9 L/sec
Standard Error 0.0
|
0.9 L/sec
Standard Error 0.0
|
0.9 L/sec
Standard Error 0.0
|
|
Peak Expiratory Flow Rate (PEFR) From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1
Peak FEF 25-75% 12hr
|
0.8 L/sec
Standard Error 0.0
|
0.9 L/sec
Standard Error 0.0
|
0.9 L/sec
Standard Error 0.0
|
0.9 L/sec
Standard Error 0.0
|
SECONDARY outcome
Timeframe: 12hr and 24hrOutcome measures
| Measure |
Placebo
n=32 Participants
Single dose of placebo administered via nebulizer
|
TD-4208 700 μg
n=31 Participants
Single dose of TD-4208 700 μg administered via nebulizer
|
TD-4208 350 μg
n=32 Participants
Single dose of TD-4208 350 μg administered via nebulizer
|
Ipratropium 500 μg
n=31 Participants
Single dose of Ipratropium 500 μg administered via nebulizer
|
|---|---|---|---|---|
|
Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1
FEF 25-75% at 12 hr
|
0.6 L/sec
Standard Error 0.0
|
0.7 L/sec
Standard Error 0.0
|
0.7 L/sec
Standard Error 0.0
|
0.6 L/sec
Standard Error 0.0
|
|
Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1
FEF 25-75% at 24 hr
|
0.6 L/sec
Standard Error 0.0
|
0.6 L/sec
Standard Error 0.0
|
0.6 L/sec
Standard Error 0.0
|
0.6 L/sec
Standard Error 0.0
|
SECONDARY outcome
Timeframe: From predose to 25 hours postdoseOutcome measures
| Measure |
Placebo
n=32 Participants
Single dose of placebo administered via nebulizer
|
TD-4208 700 μg
n=32 Participants
Single dose of TD-4208 700 μg administered via nebulizer
|
TD-4208 350 μg
n=32 Participants
Single dose of TD-4208 350 μg administered via nebulizer
|
Ipratropium 500 μg
n=32 Participants
Single dose of Ipratropium 500 μg administered via nebulizer
|
|---|---|---|---|---|
|
Forced Vital Capacity (FVC)
Predose
|
2941.9 mL
Standard Deviation 771.4
|
2949.1 mL
Standard Deviation 623.5
|
2986.7 mL
Standard Deviation 800.8
|
2959.4 mL
Standard Deviation 696.7
|
|
Forced Vital Capacity (FVC)
15 min
|
2873.4 mL
Standard Deviation 748.5
|
3166.9 mL
Standard Deviation 704.9
|
3119.3 mL
Standard Deviation 700.1
|
3339.7 mL
Standard Deviation 761.3
|
|
Forced Vital Capacity (FVC)
30 min
|
2944.7 mL
Standard Deviation 718.8
|
3263.8 mL
Standard Deviation 676.2
|
3262.2 mL
Standard Deviation 810.1
|
3399.4 mL
Standard Deviation 789.5
|
|
Forced Vital Capacity (FVC)
45 min
|
2927.2 mL
Standard Deviation 760.7
|
3324.7 mL
Standard Deviation 784.8
|
3328.8 mL
Standard Deviation 758.3
|
3394.1 mL
Standard Deviation 858.2
|
|
Forced Vital Capacity (FVC)
1 hour
|
2968.1 mL
Standard Deviation 747.3
|
3269.4 mL
Standard Deviation 801.2
|
3361.9 mL
Standard Deviation 787.3
|
3379.4 mL
Standard Deviation 829.7
|
|
Forced Vital Capacity (FVC)
2 hours
|
3062.5 mL
Standard Deviation 717.0
|
3363.1 mL
Standard Deviation 764.1
|
3408.8 mL
Standard Deviation 922.2
|
3441.6 mL
Standard Deviation 770.9
|
|
Forced Vital Capacity (FVC)
3 hours
|
3122.2 mL
Standard Deviation 774.5
|
3430.4 mL
Standard Deviation 858.6
|
3420.3 mL
Standard Deviation 912.0
|
3474.1 mL
Standard Deviation 815.1
|
|
Forced Vital Capacity (FVC)
4 hours
|
3177.8 mL
Standard Deviation 798.6
|
3386.3 mL
Standard Deviation 901.7
|
3340.9 mL
Standard Deviation 867.1
|
3368.8 mL
Standard Deviation 836.4
|
|
Forced Vital Capacity (FVC)
6 hours
|
3192.6 mL
Standard Deviation 794.3
|
3442.8 mL
Standard Deviation 849.5
|
3220.6 mL
Standard Deviation 960.7
|
3295.3 mL
Standard Deviation 889.4
|
|
Forced Vital Capacity (FVC)
8 hours
|
3197.2 mL
Standard Deviation 826.9
|
3259.4 mL
Standard Deviation 837.3
|
3301.6 mL
Standard Deviation 875.8
|
3305.2 mL
Standard Deviation 841.6
|
|
Forced Vital Capacity (FVC)
10 hours
|
2958.7 mL
Standard Deviation 686.0
|
3335.3 mL
Standard Deviation 848.5
|
3339.4 mL
Standard Deviation 749.7
|
3180.3 mL
Standard Deviation 815.5
|
|
Forced Vital Capacity (FVC)
11 hours
|
3156.2 mL
Standard Deviation 827.5
|
3296.2 mL
Standard Deviation 720.4
|
3295.5 mL
Standard Deviation 901.9
|
3162.3 mL
Standard Deviation 733.7
|
|
Forced Vital Capacity (FVC)
12 hours
|
3092.8 mL
Standard Deviation 714.8
|
3229.4 mL
Standard Deviation 859.7
|
3265.1 mL
Standard Deviation 842.1
|
3131.3 mL
Standard Deviation 737.7
|
|
Forced Vital Capacity (FVC)
14 hours
|
3114.4 mL
Standard Deviation 803.0
|
3333.1 mL
Standard Deviation 803.6
|
3319.1 mL
Standard Deviation 904.3
|
3123.8 mL
Standard Deviation 793.1
|
|
Forced Vital Capacity (FVC)
22 hours
|
3033.8 mL
Standard Deviation 669.4
|
3314.5 mL
Standard Deviation 802.1
|
3147.2 mL
Standard Deviation 754.4
|
3010.0 mL
Standard Deviation 596.6
|
|
Forced Vital Capacity (FVC)
23 hours
|
2999.7 mL
Standard Deviation 779.1
|
3349.4 mL
Standard Deviation 834.5
|
3232.2 mL
Standard Deviation 849.4
|
3006.3 mL
Standard Deviation 680.4
|
|
Forced Vital Capacity (FVC)
24 hours
|
3018.1 mL
Standard Deviation 758.2
|
3345.6 mL
Standard Deviation 810.6
|
3243.1 mL
Standard Deviation 864.9
|
3031.6 mL
Standard Deviation 703.4
|
|
Forced Vital Capacity (FVC)
25 hours
|
3172.8 mL
Standard Deviation 810.0
|
3392.5 mL
Standard Deviation 844.0
|
3295.2 mL
Standard Deviation 744.4
|
3219.4 mL
Standard Deviation 762.7
|
SECONDARY outcome
Timeframe: 0-24 hoursOutcome measures
| Measure |
Placebo
n=32 Participants
Single dose of placebo administered via nebulizer
|
TD-4208 700 μg
n=32 Participants
Single dose of TD-4208 700 μg administered via nebulizer
|
TD-4208 350 μg
n=32 Participants
Single dose of TD-4208 350 μg administered via nebulizer
|
Ipratropium 500 μg
n=32 Participants
Single dose of Ipratropium 500 μg administered via nebulizer
|
|---|---|---|---|---|
|
Area Under the Forced Vital Capacity (FVC) vs. Time Curve
|
74168.1 hr*mL
Standard Error 1155.5
|
80057.0 hr*mL
Standard Error 1155.3
|
78143.6 hr*mL
Standard Error 1155.9
|
76822.7 hr*mL
Standard Error 1155.2
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
TD-4208 700 μg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
TD-4208 350 μg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Ipratropium 500 μg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=32 participants at risk
Single dose of placebo administered via nebulizer
|
TD-4208 700 μg
n=32 participants at risk
Single dose of TD-4208 700 μg administered via nebulizer
|
TD-4208 350 μg
n=32 participants at risk
Single dose of TD-4208 350 μg administered via nebulizer
|
Ipratropium 500 μg
n=32 participants at risk
Single dose of Ipratropium 500 μg administered via nebulizer
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
18.8%
6/32 • Number of events 6 • 5 months (May-October 2011)
|
9.4%
3/32 • Number of events 3 • 5 months (May-October 2011)
|
6.2%
2/32 • Number of events 2 • 5 months (May-October 2011)
|
6.2%
2/32 • Number of events 2 • 5 months (May-October 2011)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.4%
3/32 • Number of events 3 • 5 months (May-October 2011)
|
6.2%
2/32 • Number of events 2 • 5 months (May-October 2011)
|
0.00%
0/32 • 5 months (May-October 2011)
|
12.5%
4/32 • Number of events 4 • 5 months (May-October 2011)
|
|
Infections and infestations
Nasopharyngitis
|
3.1%
1/32 • Number of events 1 • 5 months (May-October 2011)
|
0.00%
0/32 • 5 months (May-October 2011)
|
0.00%
0/32 • 5 months (May-October 2011)
|
3.1%
1/32 • Number of events 1 • 5 months (May-October 2011)
|
|
Metabolism and nutrition disorders
Gout
|
3.1%
1/32 • Number of events 1 • 5 months (May-October 2011)
|
3.1%
1/32 • Number of events 1 • 5 months (May-October 2011)
|
3.1%
1/32 • Number of events 1 • 5 months (May-October 2011)
|
3.1%
1/32 • Number of events 1 • 5 months (May-October 2011)
|
|
Investigations
Electrocardiogram T Wave peaked
|
3.1%
1/32 • Number of events 1 • 5 months (May-October 2011)
|
3.1%
1/32 • Number of events 1 • 5 months (May-October 2011)
|
6.2%
2/32 • Number of events 2 • 5 months (May-October 2011)
|
3.1%
1/32 • Number of events 1 • 5 months (May-October 2011)
|
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