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

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

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=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants	4 Participants n=7 Participants	22 Participants n=31 Participants
Age, Categorical >=65 years	1 Participants n=99 Participants	4 Participants n=107 Participants	1 Participants n=206 Participants	4 Participants n=7 Participants	10 Participants n=31 Participants
Age, Continuous	60.25 years STANDARD_DEVIATION 7.48 • n=99 Participants	63.25 years STANDARD_DEVIATION 8.21 • n=107 Participants	59.63 years STANDARD_DEVIATION 3.67 • n=206 Participants	64.88 years STANDARD_DEVIATION 7.75 • n=7 Participants	62.00 years STANDARD_DEVIATION 6.78 • n=31 Participants
Sex: Female, Male Female	3 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants	3 Participants n=7 Participants	10 Participants n=31 Participants
Sex: Female, Male Male	5 Participants n=99 Participants	6 Participants n=107 Participants	6 Participants n=206 Participants	5 Participants n=7 Participants	22 Participants n=31 Participants
Region of Enrollment New Zealand	4 participants n=99 Participants	4 participants n=107 Participants	4 participants n=206 Participants	4 participants n=7 Participants	16 participants n=31 Participants
Region of Enrollment South Africa	4 participants n=99 Participants	4 participants n=107 Participants	4 participants n=206 Participants	4 participants n=7 Participants	16 participants n=31 Participants

PRIMARY outcome

Timeframe: From predose to 25 hours postdose

Outcome measures

Outcome measures
Measure	Ipratropium 500 μg n=32 Participants Single dose of Ipratropium 500 μg administered via nebulizer	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
Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline	1883.6 mL Standard Error 32.8	1708.0 mL Standard Error 32.7	1877.3 mL Standard Error 32.7	1881.8 mL Standard Error 32.7

SECONDARY outcome

Timeframe: 12 hr and 24 hr

Outcome measures

Outcome measures
Measure	Ipratropium 500 μg n=32 Participants Single dose of Ipratropium 500 μg administered via nebulizer	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
Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo FEV1 at 12hr	1534.5 mL Standard Error 31.4	1519.2 mL Standard Error 30.9	1642.6 mL Standard Error 31.4	1631.7 mL Standard Error 30.9
Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo FEV1 at 24 hr	1509.6 mL Standard Error 22.4	1533.8 mL Standard Error 22.4	1670.4 mL Standard Error 22.4	1636.6 mL Standard Error 22.4

SECONDARY outcome

Timeframe: 12 hr and 24 hr

Outcome measures

Outcome measures
Measure	Ipratropium 500 μg n=32 Participants Single dose of Ipratropium 500 μg administered via nebulizer	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
Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo AUC 0-12 hrs	287.7 hr*mL Standard Error 4.2	262.1 hr*mL Standard Error 4.2	291.2 hr*mL Standard Error 4.2	288.5 hr*mL Standard Error 4.2
Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo AUC 0-24 hrs	271.7 hr*mL Standard Error 4.0	261.2 hr*mL Standard Error 4.0	286.6 hr*mL Standard Error 4.0	281.3 hr*mL Standard Error 4.1

SECONDARY outcome

Timeframe: 12hr and 24hr

Outcome measures

Outcome measures
Measure	Ipratropium 500 μg n=32 Participants Single dose of Ipratropium 500 μg administered via nebulizer	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
Peak Expiratory Flow Rate (PEFR) From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1 Peak FEF 25-75% 24hr	0.9 L/sec Standard Error 0.0	0.8 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	0.9 L/sec Standard Error 0.0	0.8 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 24hr

Outcome measures

Outcome measures
Measure	Ipratropium 500 μg n=31 Participants Single dose of Ipratropium 500 μg administered via nebulizer	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
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	0.6 L/sec Standard Error 0.0	0.7 L/sec Standard Error 0.0	0.7 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 postdose

Outcome measures

Outcome measures
Measure	Ipratropium 500 μg n=32 Participants Single dose of Ipratropium 500 μg administered via nebulizer	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
Forced Vital Capacity (FVC) 14 hours	3123.8 mL Standard Deviation 793.1	3114.4 mL Standard Deviation 803.0	3333.1 mL Standard Deviation 803.6	3319.1 mL Standard Deviation 904.3
Forced Vital Capacity (FVC) Predose	2959.4 mL Standard Deviation 696.7	2941.9 mL Standard Deviation 771.4	2949.1 mL Standard Deviation 623.5	2986.7 mL Standard Deviation 800.8
Forced Vital Capacity (FVC) 15 min	3339.7 mL Standard Deviation 761.3	2873.4 mL Standard Deviation 748.5	3166.9 mL Standard Deviation 704.9	3119.3 mL Standard Deviation 700.1
Forced Vital Capacity (FVC) 30 min	3399.4 mL Standard Deviation 789.5	2944.7 mL Standard Deviation 718.8	3263.8 mL Standard Deviation 676.2	3262.2 mL Standard Deviation 810.1
Forced Vital Capacity (FVC) 45 min	3394.1 mL Standard Deviation 858.2	2927.2 mL Standard Deviation 760.7	3324.7 mL Standard Deviation 784.8	3328.8 mL Standard Deviation 758.3
Forced Vital Capacity (FVC) 1 hour	3379.4 mL Standard Deviation 829.7	2968.1 mL Standard Deviation 747.3	3269.4 mL Standard Deviation 801.2	3361.9 mL Standard Deviation 787.3
Forced Vital Capacity (FVC) 2 hours	3441.6 mL Standard Deviation 770.9	3062.5 mL Standard Deviation 717.0	3363.1 mL Standard Deviation 764.1	3408.8 mL Standard Deviation 922.2
Forced Vital Capacity (FVC) 3 hours	3474.1 mL Standard Deviation 815.1	3122.2 mL Standard Deviation 774.5	3430.4 mL Standard Deviation 858.6	3420.3 mL Standard Deviation 912.0
Forced Vital Capacity (FVC) 4 hours	3368.8 mL Standard Deviation 836.4	3177.8 mL Standard Deviation 798.6	3386.3 mL Standard Deviation 901.7	3340.9 mL Standard Deviation 867.1
Forced Vital Capacity (FVC) 6 hours	3295.3 mL Standard Deviation 889.4	3192.6 mL Standard Deviation 794.3	3442.8 mL Standard Deviation 849.5	3220.6 mL Standard Deviation 960.7
Forced Vital Capacity (FVC) 8 hours	3305.2 mL Standard Deviation 841.6	3197.2 mL Standard Deviation 826.9	3259.4 mL Standard Deviation 837.3	3301.6 mL Standard Deviation 875.8
Forced Vital Capacity (FVC) 10 hours	3180.3 mL Standard Deviation 815.5	2958.7 mL Standard Deviation 686.0	3335.3 mL Standard Deviation 848.5	3339.4 mL Standard Deviation 749.7
Forced Vital Capacity (FVC) 11 hours	3162.3 mL Standard Deviation 733.7	3156.2 mL Standard Deviation 827.5	3296.2 mL Standard Deviation 720.4	3295.5 mL Standard Deviation 901.9
Forced Vital Capacity (FVC) 12 hours	3131.3 mL Standard Deviation 737.7	3092.8 mL Standard Deviation 714.8	3229.4 mL Standard Deviation 859.7	3265.1 mL Standard Deviation 842.1
Forced Vital Capacity (FVC) 22 hours	3010.0 mL Standard Deviation 596.6	3033.8 mL Standard Deviation 669.4	3314.5 mL Standard Deviation 802.1	3147.2 mL Standard Deviation 754.4
Forced Vital Capacity (FVC) 23 hours	3006.3 mL Standard Deviation 680.4	2999.7 mL Standard Deviation 779.1	3349.4 mL Standard Deviation 834.5	3232.2 mL Standard Deviation 849.4
Forced Vital Capacity (FVC) 24 hours	3031.6 mL Standard Deviation 703.4	3018.1 mL Standard Deviation 758.2	3345.6 mL Standard Deviation 810.6	3243.1 mL Standard Deviation 864.9
Forced Vital Capacity (FVC) 25 hours	3219.4 mL Standard Deviation 762.7	3172.8 mL Standard Deviation 810.0	3392.5 mL Standard Deviation 844.0	3295.2 mL Standard Deviation 744.4

SECONDARY outcome

Timeframe: 0-24 hours

Outcome measures

Outcome measures
Measure	Ipratropium 500 μg n=32 Participants Single dose of Ipratropium 500 μg administered via nebulizer	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
Area Under the Forced Vital Capacity (FVC) vs. Time Curve	76822.7 hr*mL Standard Error 1155.2	74168.1 hr*mL Standard Error 1155.5	80057.0 hr*mL Standard Error 1155.3	78143.6 hr*mL Standard Error 1155.9

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

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