Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, Age≥40 yrs, Glycopyrronium Bromide
Brief summary
This study will assess the efficacy and safety of glycopyrronium bromide (NVA237) in patients with stable COPD, in comparison to an active comparator.
Interventions
DRUGNVA237
single-dose dry-powder inhaler (SDDPI)
DRUGPlacebo
single-dose dry-powder inhaler (SDDPI)
DRUGTiotropium
Handihaler inhaler
Sponsors
Novartis Pharmaceuticals
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure. * Patients with moderate to severe COPD according to the Gold Guidelines (2006). * Patients who have smoking history of at least 10 pack years. Ten pack-years is defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc. * Patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥30% and \< 80% of the predicted normal, and post-bronchodilator FEV1/forced vital capacity (FVC) \< 0.7 at Visit 2. For non-Japanese patients predicted FEV1 should be calculated according to Quanjer predictive equations \[Quanjer PH 1993\], for Japanese patients predicted FEV1 should be calculated according to Japanese Respiratory Society predictive tables \[Japan Respiratory Society 2001\].
Exclusion criteria
* Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test). * 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 between Visit 1 and Visit 3. * Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1. Patients who develop a respiratory tract infection during the screening period (up to Visit 3) must discontinue from the trial, but will be permitted to re-enroll at a later date (at least 6 weeks after the resolution of the respiratory tract infection). * Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) unstable ischemic heart disease, cancers, left ventricular failure, long term prednisone therapy, history of myocardial infarction, arrhythmia (all), narrow angle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment. * Patients with a history of asthma indicated by (but not limited to): 1. Blood eosinophil count \> 400/mm3 2. Onset of symptoms prior to age 40 years. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment | Day 7 | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23h 15min and 23h 45min post dosing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1 | FEV1 was measured at 5, 15, 30 minutes, 1, 2, 3, 4, 5, 23 hours and 15 minutes, and 23 hours and 45 minutes post dose. |
Countries
Belgium, France, Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study | 83 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age Continuous | 64.4 years STANDARD_DEVIATION 9.05 |
| Age, Customized 40-64 years | 39 participants |
| Age, Customized >= 65 years | 44 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 25 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 58 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 55 | 4 / 51 | 1 / 53 | 2 / 54 | 3 / 55 | 2 / 54 |
| serious Total, serious adverse events | 0 / 55 | 0 / 51 | 1 / 53 | 0 / 54 | 0 / 55 | 0 / 54 |
Outcome results
Primary
Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23h 15min and 23h 45min post dosing.
Time frame: Day 7
Population: Modified Intent-to-Treat (mITT) population. The modified intent-to-treat (mITT) population included all randomized patients who received at least one dose of study drug. Patients were analyzed according to the treatment they received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 12.5 ug | Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment | 1.317 Liters | Standard Error 0.0145 |
| NVA237 25 ug | Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment | 1.333 Liters | Standard Error 0.0151 |
| NVA237 50 ug | Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment | 1.374 Liters | Standard Error 0.0148 |
| NVA237 100 ug | Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment | 1.385 Liters | Standard Error 0.0148 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment | 1.243 Liters | Standard Error 0.0156 |
| Tiotropium Bromide | Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment | 1.370 Liters | Standard Error 0.0145 |
Secondary
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
FEV1 was measured at 5, 15, 30 minutes, 1, 2, 3, 4, 5, 23 hours and 15 minutes, and 23 hours and 45 minutes post dose.
Time frame: Day 1
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 15 minutes | 1.36 Liters | Standard Error 0.01 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 hours | 1.39 Liters | Standard Error 0.01 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 1 hour | 1.42 Liters | Standard Error 0.01 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 15 minutes | 1.27 Liters | Standard Error 0.01 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 minutes | 1.30 Liters | Standard Error 0.01 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -45 minutes | 1.25 Liters | Standard Error 0 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 2 hours | 1.44 Liters | Standard Error 0.01 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 3 hours | 1.43 Liters | Standard Error 0.01 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 30 minutes | 1.41 Liters | Standard Error 0.01 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Trough | 1.28 Liters | Standard Error 0.01 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 45 minutes | 1.29 Liters | Standard Error 0.01 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -15 minutes | 1.25 Liters | Standard Error 0 |
| NVA237 12.5 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 4 hours | 1.41 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -45 minutes | 1.24 Liters | Standard Error 0 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 2 hours | 1.48 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 3 hours | 1.48 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -15 minutes | 1.26 Liters | Standard Error 0 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 45 minutes | 1.31 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 minutes | 1.34 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Trough | 1.30 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 15 minutes | 1.29 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 15 minutes | 1.41 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 hours | 1.43 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 30 minutes | 1.44 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 4 hours | 1.45 Liters | Standard Error 0.01 |
| NVA237 25 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 1 hour | 1.46 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 45 minutes | 1.37 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 hours | 1.44 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 2 hours | 1.50 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Trough | 1.36 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 3 hours | 1.49 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 30 minutes | 1.44 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 minutes | 1.34 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -45 minutes | 1.24 Liters | Standard Error 0 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 4 hours | 1.49 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 15 minutes | 1.36 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -15 minutes | 1.25 Liters | Standard Error 0 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 1 hour | 1.46 Liters | Standard Error 0.01 |
| NVA237 50 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 15 minutes | 1.41 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 hours | 1.49 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -45 minutes | 1.24 Liters | Standard Error 0 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -15 minutes | 1.26 Liters | Standard Error 0 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 minutes | 1.35 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 15 minutes | 1.41 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 30 minutes | 1.45 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 1 hour | 1.48 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 2 hours | 1.52 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 3 hours | 1.53 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 4 hours | 1.52 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 15 minutes | 1.37 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 45 minutes | 1.39 Liters | Standard Error 0.01 |
| NVA237 100 ug | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Trough | 1.38 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 4 hours | 1.30 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 15 minutes | 1.24 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -15 minutes | 1.26 Liters | Standard Error 0 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 hours | 1.28 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Trough | 1.24 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 45 minutes | 1.25 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 1 hour | 1.28 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -45 minutes | 1.24 Liters | Standard Error 0 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 30 minutes | 1.28 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 2 hours | 1.31 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 minutes | 1.26 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 15 minutes | 1.27 Liters | Standard Error 0.01 |
| Placebo | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 3 hours | 1.30 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Trough | 1.36 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 30 minutes | 1.40 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 4 hours | 1.46 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 15 minutes | 1.35 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 hours | 1.45 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 5 minutes | 1.31 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -15 minutes | 1.25 Liters | Standard Error 0 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 3 hours | 1.46 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: -45 minutes | 1.25 Liters | Standard Error 0 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 45 minutes | 1.37 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 2 hours | 1.45 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 1 hour | 1.41 Liters | Standard Error 0.01 |
| Tiotropium Bromide | Least Squares Means of FEV1 (L) at Day 1, by Timepoint | Day 1: 23 hours 15 minutes | 1.35 Liters | Standard Error 0.01 |