Chronic Obstructive Pulmonary Disease, COPD
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD
Brief summary
This study evaluated the safety and efficacy of once and twice daily TD-4208 and placebo when administered using a jet nebulizer for 7 days in a cross-over design to patients with moderate to severe chronic obstructive pulmonary disease.
Interventions
DRUGPlacebo
DRUGTD-4208
Sponsors
Theravance Biopharma
Mylan Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject must have a negative pregnancy test, and must be prepared to use effective contraception if of child-bearing potential * Subject is capable of performing reproducible spirometry maneuvers * Subject has post-bronchodilator FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) ratio \<0.7 * Subject has moderate-to-severe stable COPD (Stage 2 or 3 according to the Global Initiative for the Treatment of Obstructive Lung Disease (GOLD) Guidelines) * Subject has a post-bronchodilator FEV1 greater than or equal to 30% and less than 80% of predicted normal * Subject demonstrates a post-ipratropium FEV1 response ≥ 12% and ≥ 200 mL of pre-ipratropium FEV1 response * Subject has a current or past smoking history of at least 10 pack-years.
Exclusion criteria
* Subject has a significant respiratory disease or disorder other than COPD that would affect the interpretation of data from this study * Subject has a history of reactions or hypersensitivity to inhaled anticholinergic or beta-agonist agents * Subject suffers from any medical condition that would preclude the use of inhaled anticholinergic agents * Subject has been hospitalized for COPD or pneumonia within 12 weeks. * Subject requires long-term oxygen therapy (\>15 hours a day)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Mean (0-24hr) Change From Baseline FEV1 (Forced Expiratory Volume in 1 Second) | Following the Day 7 AM dose -12 hours post-dose and 24 hours post-dose | Weighted mean (0-24hr) Change from baseline FEV1 (forced expiratory volume in 1 second). Measurement is change from baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All groups were randomized to receive placebo, TD-4208 44mcg twice daily, and TD-4208 175 mcg once daily | 64 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 25 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 64 | 24 / 64 | 14 / 64 |
| serious Total, serious adverse events | 0 / 64 | 0 / 64 | 1 / 64 |
Outcome results
Primary
Weighted Mean (0-24hr) Change From Baseline FEV1 (Forced Expiratory Volume in 1 Second)
Weighted mean (0-24hr) Change from baseline FEV1 (forced expiratory volume in 1 second). Measurement is change from baseline.
Time frame: Following the Day 7 AM dose -12 hours post-dose and 24 hours post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weighted Mean (0-24hr) Change From Baseline FEV1 (Forced Expiratory Volume in 1 Second) | -14.4 mL | Standard Error 15.29 |
| TD-4208 44 mcg Twice Daily | Weighted Mean (0-24hr) Change From Baseline FEV1 (Forced Expiratory Volume in 1 Second) | 90.2 mL | Standard Error 15 |
| TD-4208 175 mcg Once Daily | Weighted Mean (0-24hr) Change From Baseline FEV1 (Forced Expiratory Volume in 1 Second) | 98.5 mL | Standard Error 15.03 |