Chronic Obstructive Pulmonary Disease, COPD
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD
Brief summary
Thirty-two subjects diagnosed with COPD were enrolled, received each study treatment and completed the follow-up assessments. During each of the four study periods, subjects were admitted to the clinic on Day -1 and housed overnight until after the last spirometry measurement. Serial pulmonary function tests were performed and PK (pharmacokinetics) samples collected up to 25 hours. Subjects were discharged from the clinic on Day 2 after evaluations.
Detailed description
Subjects were assigned to one of the 4-treatment sequence groups presented in the table above according to a randomization schedule supplied by the Sponsor before study initiation. The randomization scheme did not include assignments for replacement subjects. Subjects reported to their respective clinical research unit (CRU) on Admission/Day -1 for pre-randomization procedures and confirmation of eligibility (and continued eligibility for Periods 2 to 4). The unblinded pharmacist prepared and dispensed the nebulizers, according to the randomization schedule for each of the 4 periods. Dosing occurred in the morning, generally between 7 am and 9 am. For Periods 2 to 4, dosing occurred within ±30 minutes of the dosing time established in Period 1. Study drug was administered in the respective CRU under the supervision of study personnel. Single doses of TD-4208, ipratropium bromide, and placebo were administered in the clinical research unit (CRU) under the supervision of study personnel. Care was taken to avoid eye contact with study drugs. Residual drug solution remaining in the nebulizer (ie, in mL) was measured and recorded. The investigator or designee was responsible for maintaining accountability records for all study drug(s) in accordance with applicable government regulations and study procedures. The accountability record included entries for receipt, distribution or dispensing, and destruction of the material(s). Unused and expired study drugs were to be disposed of in accordance with written instructions from the Sponsor.
Interventions
DRUGPlacebo
DRUGTD-4208 700 μg
DRUGTD-4208 350 μg
DRUGIpratropium 500 μg
Sponsors
Theravance Biopharma
Mylan Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of moderate stable Chronic Obstructive Pulmonary. * Disease with FEV1/FVC \<0.7 at screening. * Woman of non-childbearing potential. * Female participants of childbearing potential must test negative for pregnancy and must be using a highly effective method of birth control during the study and for at least 1 month after completion of study dosing. * Female participants must not be breastfeeding. * Men must agree to use a highly effective method of birth control with partners of childbearing potential during the study and for 1 month after completion of study dosing. * Current or past smoking history \>10 pack-years. * Must be capable of performing reproducible spirometry maneuvers.
Exclusion criteria
* History of significant respiratory disease other than COPD, and/ or requires daily long-term oxygen therapy. * Exacerbation of COPD, lung infection within 6 weeks prior to study. * Start of or change in dose of COPD treatment 4 weeks before study. * Daily using of maintenance systemic/inhaled corticosteroids (\>1000 microgram of fluticasone propionate equivalent or \>5 mg prednisone). * Use of bronchodilators or medication for the treatment of COPD, aspirin, anti-inflammatories for a specific time, prior to the first dose or is not willing to abstain from their use for the specified time periods prior to study dose administration. * Symptomatic prostrate hypertrophy, bladder neck obstruction, active cancer, narrow angle glaucoma. * Clinical significant hypersensitivity to medications. * Participants have an uncontrolled hematologic, immunologic, renal, neurologic, hepatic, endocrine or other disease that may place participant at risk. * Cerebrovascular, cardiovascular disease or abnormal ECG. * History of drug or alcohol abuse.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline | From predose to 25 hours postdose |
Secondary
| Measure | Time frame |
|---|---|
| Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo | 12 hr and 24 hr |
| Peak Expiratory Flow Rate (PEFR) From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1 | 12hr and 24hr |
| Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo | 12 hr and 24 hr |
| Forced Vital Capacity (FVC) | From predose to 25 hours postdose |
| Area Under the Forced Vital Capacity (FVC) vs. Time Curve | 0-24 hours |
| Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1 | 12hr and 24hr |
Countries
New Zealand
Participant flow
Recruitment details
21-May-2011 (FPFV) through 07-Oct-2011 (LPLV)
Pre-assignment details
Male and female subjects between the ages of 40 and 75 years-old with a clinical diagnosis of COPD and responsiveness to ipratropium bromide.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 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 \[7 days\] | 8 |
| 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 \[7 days\] | 8 |
| 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 \[7 days\] | 8 |
| 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 \[7 days\] | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | Sequence 1 | Sequence 2 | Sequence 3 | Sequence 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 4 Participants | 1 Participants | 4 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 4 Participants | 7 Participants | 4 Participants | 22 Participants |
| Age, Continuous | 60.25 years STANDARD_DEVIATION 7.48 | 63.25 years STANDARD_DEVIATION 8.21 | 59.63 years STANDARD_DEVIATION 3.67 | 64.88 years STANDARD_DEVIATION 7.75 | 62.00 years STANDARD_DEVIATION 6.78 |
| Region of Enrollment New Zealand | 4 participants | 4 participants | 4 participants | 4 participants | 16 participants |
| Region of Enrollment South Africa | 4 participants | 4 participants | 4 participants | 4 participants | 16 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 10 / 32 | 6 / 32 | 4 / 32 | 7 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 |
Outcome results
Primary
Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline
Time frame: From predose to 25 hours postdose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline | 1708.0 mL | Standard Error 32.7 |
| TD-4208 700 μg | Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline | 1877.3 mL | Standard Error 32.7 |
| TD-4208 350 μg | Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline | 1881.8 mL | Standard Error 32.7 |
| Ipratropium 500 μg | Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline | 1883.6 mL | Standard Error 32.8 |
p-value: <0.00195% CI: [112.4, 235.3]t-test, 2 sided
p-value: <0.00195% CI: [107.8, 230.8]t-test, 2 sided
p-value: <0.00195% CI: [114.1, 237.2]t-test, 2 sided
Secondary
Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo
Time frame: 12 hr and 24 hr
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo | AUC 0-12 hrs | 262.1 hr*mL | Standard Error 4.2 |
| Placebo | Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo | AUC 0-24 hrs | 261.2 hr*mL | Standard Error 4 |
| TD-4208 700 μg | Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo | AUC 0-24 hrs | 286.6 hr*mL | Standard Error 4 |
| TD-4208 700 μg | Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo | AUC 0-12 hrs | 291.2 hr*mL | Standard Error 4.2 |
| TD-4208 350 μg | Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo | AUC 0-12 hrs | 288.5 hr*mL | Standard Error 4.2 |
| TD-4208 350 μg | Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo | AUC 0-24 hrs | 281.3 hr*mL | Standard Error 4.1 |
| Ipratropium 500 μg | Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo | AUC 0-12 hrs | 287.7 hr*mL | Standard Error 4.2 |
| Ipratropium 500 μg | Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo | AUC 0-24 hrs | 271.7 hr*mL | Standard Error 4 |
Comparison: Tx Difference of LS Mean AUC, 0-12 hrsp-value: <0.00195% CI: [18, 34.8]t-test, 2 sided
Comparison: Tx Difference of LS Mean AUC, 0-12 hrsp-value: <0.00195% CI: [20.8, 37.4]t-test, 2 sided
Comparison: Tx Difference of LS Mean AUC, 0-12 hrsp-value: <0.00195% CI: [17.3, 33.9]t-test, 2 sided
Comparison: Tx Difference of LS Mean AUC, 0-24 hrsp-value: <0.00195% CI: [12.1, 28.2]t-test, 2 sided
Comparison: Tx Difference of LS Mean AUC, 0-24 hrsp-value: <0.00195% CI: [17.4, 33.4]t-test, 2 sided
Comparison: Tx Difference of LS Mean AUC, 0-24 hrp-value: 0.0195% CI: [2.5, 18.6]t-test, 2 sided
Secondary
Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo
Time frame: 12 hr and 24 hr
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo | FEV1 at 12hr | 1519.2 mL | Standard Error 30.9 |
| Placebo | Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo | FEV1 at 24 hr | 1533.8 mL | Standard Error 22.4 |
| TD-4208 700 μg | Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo | FEV1 at 24 hr | 1670.4 mL | Standard Error 22.4 |
| TD-4208 700 μg | Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo | FEV1 at 12hr | 1642.6 mL | Standard Error 31.4 |
| TD-4208 350 μg | Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo | FEV1 at 12hr | 1631.7 mL | Standard Error 30.9 |
| TD-4208 350 μg | Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo | FEV1 at 24 hr | 1636.6 mL | Standard Error 22.4 |
| Ipratropium 500 μg | Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo | FEV1 at 12hr | 1534.5 mL | Standard Error 31.4 |
| Ipratropium 500 μg | Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo | FEV1 at 24 hr | 1509.6 mL | Standard Error 22.4 |
Comparison: Tx Difference of LS Mean FEV1 at 12 hrp-value: 0.00195% CI: [44.5, 180.5]t-test, 2 sided
Comparison: Tx Difference of LS Mean FEV1 at 12 hrp-value: <0.00195% CI: [54.6, 192.3]t-test, 2 sided
Comparison: Tx Difference of LS Mean FEV1 at 12 hrp-value: 0.65995% CI: [-53.5, 94.1]t-test, 2 sided
Comparison: Tx Difference of LS Mean FEV1 at 24 hrp-value: <0.00195% CI: [54.1, 151.5]t-test, 2 sided
Comparison: Tx Difference of LS Mean FEV1 at 24 hrp-value: <0.00195% CI: [87.8, 185.3]t-test, 2 sided
p-value: 0.32795% CI: [-72.9, 24.6]t-test, 2 sided
Secondary
Area Under the Forced Vital Capacity (FVC) vs. Time Curve
Time frame: 0-24 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Forced Vital Capacity (FVC) vs. Time Curve | 74168.1 hr*mL | Standard Error 1155.5 |
| TD-4208 700 μg | Area Under the Forced Vital Capacity (FVC) vs. Time Curve | 80057.0 hr*mL | Standard Error 1155.3 |
| TD-4208 350 μg | Area Under the Forced Vital Capacity (FVC) vs. Time Curve | 78143.6 hr*mL | Standard Error 1155.9 |
| Ipratropium 500 μg | Area Under the Forced Vital Capacity (FVC) vs. Time Curve | 76822.7 hr*mL | Standard Error 1155.2 |
p-value: <0.00195% CI: [2007.3, 5943.7]t-test, 2 sided
p-value: <0.00195% CI: [3924.4, 7853.4]t-test, 2 sided
p-value: 0.00995% CI: [689.7, 4619.6]t-test, 2 sided
Secondary
Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1
Time frame: 12hr and 24hr
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| TD-4208 700 μg | 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 |
| TD-4208 700 μg | Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1 | FEF 25-75% at 12 hr | 0.7 L/sec | Standard Error 0 |
| TD-4208 350 μg | Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1 | FEF 25-75% at 12 hr | 0.7 L/sec | Standard Error 0 |
| TD-4208 350 μg | 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 |
| Ipratropium 500 μg | 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 |
| Ipratropium 500 μg | 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 |
Comparison: Tx Difference of LS Mean 12 hrp-value: 0.05495% CI: [0, 0.1]t-test, 2 sided
Comparison: Tx Difference of LS Mean 12 hrp-value: 0.04595% CI: [0, 0.2]t-test, 2 sided
Comparison: Tx Difference of LS Mean 12 hrp-value: 0.50395% CI: [0, 0.1]t-test, 2 sided
Comparison: Tx Difference of LS Mean 24 hrp-value: 0.18395% CI: [0, 0.1]t-test, 2 sided
Comparison: Tx Difference of LS Mean 24 hrp-value: 0.42295% CI: [0, 0.1]t-test, 2 sided
Comparison: Tx Difference of LS Mean 24 hrp-value: 0.28795% CI: [-0.1, 0]t-test, 2 sided
Secondary
Forced Vital Capacity (FVC)
Time frame: From predose to 25 hours postdose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) | 23 hours | 2999.7 mL | Standard Deviation 779.1 |
| Placebo | Forced Vital Capacity (FVC) | 11 hours | 3156.2 mL | Standard Deviation 827.5 |
| Placebo | Forced Vital Capacity (FVC) | 1 hour | 2968.1 mL | Standard Deviation 747.3 |
| Placebo | Forced Vital Capacity (FVC) | 22 hours | 3033.8 mL | Standard Deviation 669.4 |
| Placebo | Forced Vital Capacity (FVC) | 14 hours | 3114.4 mL | Standard Deviation 803 |
| Placebo | Forced Vital Capacity (FVC) | 12 hours | 3092.8 mL | Standard Deviation 714.8 |
| Placebo | Forced Vital Capacity (FVC) | 45 min | 2927.2 mL | Standard Deviation 760.7 |
| Placebo | Forced Vital Capacity (FVC) | 6 hours | 3192.6 mL | Standard Deviation 794.3 |
| Placebo | Forced Vital Capacity (FVC) | 2 hours | 3062.5 mL | Standard Deviation 717 |
| Placebo | Forced Vital Capacity (FVC) | 30 min | 2944.7 mL | Standard Deviation 718.8 |
| Placebo | Forced Vital Capacity (FVC) | 15 min | 2873.4 mL | Standard Deviation 748.5 |
| Placebo | Forced Vital Capacity (FVC) | 8 hours | 3197.2 mL | Standard Deviation 826.9 |
| Placebo | Forced Vital Capacity (FVC) | 4 hours | 3177.8 mL | Standard Deviation 798.6 |
| Placebo | Forced Vital Capacity (FVC) | Predose | 2941.9 mL | Standard Deviation 771.4 |
| Placebo | Forced Vital Capacity (FVC) | 25 hours | 3172.8 mL | Standard Deviation 810 |
| Placebo | Forced Vital Capacity (FVC) | 10 hours | 2958.7 mL | Standard Deviation 686 |
| Placebo | Forced Vital Capacity (FVC) | 3 hours | 3122.2 mL | Standard Deviation 774.5 |
| Placebo | Forced Vital Capacity (FVC) | 24 hours | 3018.1 mL | Standard Deviation 758.2 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 3 hours | 3430.4 mL | Standard Deviation 858.6 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 4 hours | 3386.3 mL | Standard Deviation 901.7 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 6 hours | 3442.8 mL | Standard Deviation 849.5 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 8 hours | 3259.4 mL | Standard Deviation 837.3 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 10 hours | 3335.3 mL | Standard Deviation 848.5 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 11 hours | 3296.2 mL | Standard Deviation 720.4 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 12 hours | 3229.4 mL | Standard Deviation 859.7 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 14 hours | 3333.1 mL | Standard Deviation 803.6 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 22 hours | 3314.5 mL | Standard Deviation 802.1 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 23 hours | 3349.4 mL | Standard Deviation 834.5 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 24 hours | 3345.6 mL | Standard Deviation 810.6 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 25 hours | 3392.5 mL | Standard Deviation 844 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | Predose | 2949.1 mL | Standard Deviation 623.5 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 15 min | 3166.9 mL | Standard Deviation 704.9 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 30 min | 3263.8 mL | Standard Deviation 676.2 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 45 min | 3324.7 mL | Standard Deviation 784.8 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 1 hour | 3269.4 mL | Standard Deviation 801.2 |
| TD-4208 700 μg | Forced Vital Capacity (FVC) | 2 hours | 3363.1 mL | Standard Deviation 764.1 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 3 hours | 3420.3 mL | Standard Deviation 912 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 23 hours | 3232.2 mL | Standard Deviation 849.4 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 10 hours | 3339.4 mL | Standard Deviation 749.7 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 1 hour | 3361.9 mL | Standard Deviation 787.3 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 24 hours | 3243.1 mL | Standard Deviation 864.9 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 25 hours | 3295.2 mL | Standard Deviation 744.4 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 8 hours | 3301.6 mL | Standard Deviation 875.8 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | Predose | 2986.7 mL | Standard Deviation 800.8 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 15 min | 3119.3 mL | Standard Deviation 700.1 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 6 hours | 3220.6 mL | Standard Deviation 960.7 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 2 hours | 3408.8 mL | Standard Deviation 922.2 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 30 min | 3262.2 mL | Standard Deviation 810.1 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 45 min | 3328.8 mL | Standard Deviation 758.3 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 12 hours | 3265.1 mL | Standard Deviation 842.1 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 14 hours | 3319.1 mL | Standard Deviation 904.3 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 11 hours | 3295.5 mL | Standard Deviation 901.9 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 4 hours | 3340.9 mL | Standard Deviation 867.1 |
| TD-4208 350 μg | Forced Vital Capacity (FVC) | 22 hours | 3147.2 mL | Standard Deviation 754.4 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 11 hours | 3162.3 mL | Standard Deviation 733.7 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 45 min | 3394.1 mL | Standard Deviation 858.2 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 22 hours | 3010.0 mL | Standard Deviation 596.6 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 30 min | 3399.4 mL | Standard Deviation 789.5 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 4 hours | 3368.8 mL | Standard Deviation 836.4 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 24 hours | 3031.6 mL | Standard Deviation 703.4 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 8 hours | 3305.2 mL | Standard Deviation 841.6 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 1 hour | 3379.4 mL | Standard Deviation 829.7 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 2 hours | 3441.6 mL | Standard Deviation 770.9 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 25 hours | 3219.4 mL | Standard Deviation 762.7 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 14 hours | 3123.8 mL | Standard Deviation 793.1 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 3 hours | 3474.1 mL | Standard Deviation 815.1 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 10 hours | 3180.3 mL | Standard Deviation 815.5 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | Predose | 2959.4 mL | Standard Deviation 696.7 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 6 hours | 3295.3 mL | Standard Deviation 889.4 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 23 hours | 3006.3 mL | Standard Deviation 680.4 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 12 hours | 3131.3 mL | Standard Deviation 737.7 |
| Ipratropium 500 μg | Forced Vital Capacity (FVC) | 15 min | 3339.7 mL | Standard Deviation 761.3 |
Secondary
Peak Expiratory Flow Rate (PEFR) From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1
Time frame: 12hr and 24hr
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| TD-4208 700 μg | 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 |
| TD-4208 700 μg | 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 |
| TD-4208 350 μg | 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 |
| TD-4208 350 μg | 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 |
| Ipratropium 500 μg | 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 |
| Ipratropium 500 μg | 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 |
Comparison: Tx Difference of LS Mean 12 hrp-value: 0.00395% CI: [0, 0.2]t-test, 2 sided
Comparison: Tx Difference of LS Mean 12 hrp-value: 0.04695% CI: [0, 0.2]t-test, 2 sided
Comparison: Tx Difference of LS Mean 12 hrp-value: 0.00395% CI: [0, 0.2]t-test, 2 sided
Comparison: Tx Difference of LS Mean 24 hrp-value: 0.00395% CI: [0, 0.2]t-test, 2 sided
Comparison: Tx Difference of LS Mean 24 hrp-value: 0.04895% CI: [0, 0.2]t-test, 2 sided
Comparison: Tx Difference of LS Mean 24 hrp-value: 0.00795% CI: [0, 0.2]t-test, 2 sided