Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, glycopyrronium bromide, antimuscarinic
Brief summary
This study assessed the safety/tolerability of 28 days of treatment with NVA237 100 µg and 200 µg once a day, compared to placebo in patients with moderate or severe Chronic Obstructive Pulmonary Disease (COPD).
Interventions
DRUGNVA237 100 µg
Dry powder inhalation once a day for up to 28 days
DRUGPlacebo
Placebo to NVA237 dry powder inhalation once a day for up to 28 days
DRUGNVA237 200 µg
Dry powder inhalation once a day for up to 28 days
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female adults aged 40 years or older * Patients with moderate to severe COPD according to the GOLD Guidelines (2006) * Patients who have smoking history of at least 10 pack years * Patients with a post-bronchodilator Forced Expiratory Volume in One Second (FEV1) equal or greater than 30% of the predicted normal value and less than 80% of the predicted normal value, and post-bronchodilator FEV1/FVC less than 0.7 at visit 2 * Written informed consent by the patient prior to initiation of any study-related procedure
Exclusion criteria
* Patients requiring oxygen therapy on a daily basis for chronic hypoxemia, or who have been hospitalized for an exacerbation of their airways disease in the 6 weeks prior to visit 1 or during the screening period (up to visit 3). * Patients who have had a respiratory tract infection within 6 weeks prior to visit 1 or during the screening period (up to visit 3). * Patients with a history of asthma indicated by (but not limited to): Blood eosinophil count \> 400/mm3, onset of symptoms prior to age 40 years. * Patients with a history of long QT syndrome or whose QTc measured at visit 1 is prolonged (more than 440 ms for males or more than 460 ms for females). * Patients with a history of untoward reactions to sympathomimetic amines or inhaled medication or any component thereof. * Patients who, in the judgment of the investigator have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) unstable ischemic heart disease, left ventricular failure, long term prednisone therapy, history of myocardial infarction, arrhythmia, narrow-angle glaucoma, symptomatic prostatic hyperplasia, bladder-neck obstruction or moderate to severe renal impairment that might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study. * History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Treatment With NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) | 28 days | The assessment of safety was based on adverse events, particularly those adverse events known to be associated to treatment with muscarinic antagonists. A summary of adverse events is presented with this outcome, additional details are provided in Adverse Events Sections. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Means of Trough Forced Expiratory Volume in One Second (FEV1), by Day | 28 Days | Forced expiratory volume maneuvers recorded using a calibrated spirometer. Trough forced expiratory volume in one second (FEV1) on Days 1 & 28 defined as the mean of the FEV1 values measured at 23 hours 15 minutes and 23 hours 45 minutes post-dose. |
Countries
France, Germany, Netherlands, Spain, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NVA237 100 µg NVA237 100 µg as a single dose dry powder inhaler (SDDPI), once a day in the morning for 28 days.. | 92 |
| NVA237 200 µg NVA237 200 µg as a single dose dry powder inhaler (SDDPI), once a day in the morning for 28 days. | 98 |
| Placebo Matching placebo to NVA237 as a single dose dry powder inhaler (SDDPI), once a day in the morning for 28 days. | 91 |
| Total | 281 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 | 6 |
| Overall Study | Lack of Efficacy | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 3 | 4 |
| Overall Study | Subjects no longer requires study drug | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 3 |
Baseline characteristics
| Characteristic | NVA237 100 µg | NVA237 200 µg | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 64.2 years STANDARD_DEVIATION 7.93 | 62.6 years STANDARD_DEVIATION 9.04 | 63.4 years STANDARD_DEVIATION 9.44 | 63.4 years STANDARD_DEVIATION 8.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 15 Participants | 11 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants | 79 Participants | 76 Participants | 227 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 90 Participants | 94 Participants | 88 Participants | 272 Participants |
| Sex: Female, Male Female | 35 Participants | 29 Participants | 27 Participants | 91 Participants |
| Sex: Female, Male Male | 57 Participants | 69 Participants | 64 Participants | 190 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 | 7 / 92 | 10 / 98 | 4 / 91 |
| serious Total, serious adverse events | 0 / 92 | 1 / 98 | 1 / 91 |
Outcome results
Primary
Safety of Treatment With NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
The assessment of safety was based on adverse events, particularly those adverse events known to be associated to treatment with muscarinic antagonists. A summary of adverse events is presented with this outcome, additional details are provided in Adverse Events Sections.
Time frame: 28 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVA237 100 µg | Safety of Treatment With NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) | Total number of patients with any AE | 26 Participants |
| NVA237 100 µg | Safety of Treatment With NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) | Total number with any significant AE | 3 Participants |
| NVA237 200 µg | Safety of Treatment With NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) | Total number with any significant AE | 4 Participants |
| NVA237 200 µg | Safety of Treatment With NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) | Total number of patients with any AE | 26 Participants |
| Placebo | Safety of Treatment With NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) | Total number of patients with any AE | 24 Participants |
| Placebo | Safety of Treatment With NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) | Total number with any significant AE | 6 Participants |
Secondary
Least Squares Means of Trough Forced Expiratory Volume in One Second (FEV1), by Day
Forced expiratory volume maneuvers recorded using a calibrated spirometer. Trough forced expiratory volume in one second (FEV1) on Days 1 & 28 defined as the mean of the FEV1 values measured at 23 hours 15 minutes and 23 hours 45 minutes post-dose.
Time frame: 28 Days
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 100 µg | Least Squares Means of Trough Forced Expiratory Volume in One Second (FEV1), by Day | Trough FEV1 Day 1 | 1.465 Liters | Standard Error 0.0152 |
| NVA237 100 µg | Least Squares Means of Trough Forced Expiratory Volume in One Second (FEV1), by Day | Trough FEV1 Day 28 | 1.502 Liters | Standard Error 0.0182 |
| NVA237 200 µg | Least Squares Means of Trough Forced Expiratory Volume in One Second (FEV1), by Day | Trough FEV1 Day 1 | 1.480 Liters | Standard Error 0.0149 |
| NVA237 200 µg | Least Squares Means of Trough Forced Expiratory Volume in One Second (FEV1), by Day | Trough FEV1 Day 28 | 1.492 Liters | Standard Error 0.018 |
| Placebo | Least Squares Means of Trough Forced Expiratory Volume in One Second (FEV1), by Day | Trough FEV1 Day 28 | 1.341 Liters | Standard Error 0.02 |
| Placebo | Least Squares Means of Trough Forced Expiratory Volume in One Second (FEV1), by Day | Trough FEV1 Day 1 | 1.334 Liters | Standard Error 0.0154 |