Efficacy and Safety of NVA237 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01119950
First received: May 5, 2010
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

This study was designed to investigate the efficacy and safety of NVA237, a long-acting muscarinic antagonist, in patients with moderate to severe COPD.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: NVA237 12.5 µg once daily
Drug: NVA237 25.0 µg once daily
Drug: NVA237 12.5 µg twice daily
Drug: NVA237 50.0 µg once daily
Drug: NVA237 25.0 µg twice daily
Drug: NVA237 100.0 µg once daily
Drug: NVA237 50.0 µg twice daily
Drug: Placebo to NVA237 once daily
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, 2-period, Cross-over Study to Assess the Efficacy and Safety of Differing Doses of NVA237 Administered Either Once Daily or Twice Daily, in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. The maximal response of incremental once daily and twice daily doses of NVA237 that each dose achieves in relation to the maximal effect of NVA237 on Trough FEV1 was measured at Day 28. FEV1 was measured in response to all doses administered (see Outcome Measure #19).

    All trough FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All trough FEV1 data are reported as a percentage of the theoretical maximal response.

    Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values.



Secondary Outcome Measures:
  • Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237 [ Time Frame: day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer.

    FEV1 was measured between dosing regimens (over the range 20 micrograms to 55 micrograms total daily dose) after 28 days of treatment.

    Mean trough FEV1 was measured in response to all doses administered (12.5 µg q.d., 25.0 µg q.d., 12.5 µg b.i.d., 50 µg q.d., 25 µg b.i.d., 100 µg q.d., 50.0 µg b.i.d., and Placebo; see Outcome Measure # 19), and was used to compute modeled dose-response curves for once-daily and twice-daily regimens separately. The difference between those curves was computed at pre-specified theoretical doses (20 µg, 25 µg, 30 µg, 35 µg, 40 µg, 45 µg, 50 µg, and 55 µg) chosen at points likely to show the largest differences between the once-daily and twice-daily regimens. The theoretical responses to each dosing schedule separately and the difference between the once-daily and twice-daily regimens are represented below.


  • Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment [ Time Frame: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer.

    Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-24 hours at day 28 of treatment was calculated from measurements taken at 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28.

    AUC FEV1 was measured in response to all doses administered (see Outcome Measure #20). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment [ Time Frame: -25 min,-15 min (predose); 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer.

    The Area Under the Curve (AUC) 0-24 hours FEV1 between dosing regimens over the range 20 micrograms to 55 micrograms total daily dose at -25 min,-15 min (predose); 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28.

    AUC 0-24 hours FEV1 was measured in response to all doses administered (12.5 µg q.d., 25.0 µg q.d., 12.5 µg b.i.d., 50 µg q.d., 25 µg b.i.d., 100 µg q.d., 50.0 µg b.i.d., and Placebo; see Outcome Measure # 20), and was used to compute modeled dose-response curves for once-daily and twice-daily regimens separately. The difference between those curves was computed at pre-specified theoretical doses (20 µg, 25 µg, 30 µg, 35 µg, 40 µg, 45 µg, 50 µg, and 55 µg) chosen at points likely to show the largest differences between the once-daily and twice-daily regimens.


  • Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 [ Time Frame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer.

    Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours were calculated from measurements taken at: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28.

    AUC FEV1 was measured in response to all doses administered (see Outcome Measure #21). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment [ Time Frame: 12 hours on day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response within different doses/regimens of NVA237 was measured using FEV1 at 12 hours on day 28 of treatment.

    FEV1 was measured in response to all doses administered (see Outcome Measure #22). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment [ Time Frame: day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time.

    Percentage of the maximal response of NVA237 within different doses/regimens of NVA237 on Peak FEV1 was measured at day 28 of treatment.

    Peak FEV1 was measured in response to all doses administered (see Outcome Measure #23). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment [ Time Frame: day 28 ] [ Designated as safety issue: No ]

    Percentage of the maximal response of NVA237 within different doses/regimens of NVA237 on Forced Vital Capacity (FVC) was measured at day 28 of treatment. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

    FVC at day 28 of treatment was measured via spirometry (see Outcome Measure #24). All FVC responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FVC data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 [ Time Frame: Days 1, 7 and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on Trough FEV1 was measured on Days 1, 7 and 14.

    Through FEV1 was measured in response to all doses administered (see Outcome Measure #25). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.

    Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values.


  • Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment [ Time Frame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer.

    Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-24 hours, was calculated from measurements taken at 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14.

    FEV1 AUC 0-24 hours was measured on days 1 and 14 of treatment in response to all doses administered (see Outcome Measure #26). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment [ Time Frame: 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer.

    Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-4 hours was calculated from measurements taken at 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14, in response to all doses administered (see Outcome Measure #27).

    All AUC FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 [ Time Frame: at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7 and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-8 was calculated from measurements taken at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7, and 14.

    AUC FEV1 was measured in response to all doses administered (see Outcome Measure #28). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment [ Time Frame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses was calculated on FEV1 Area Under the Curve (AUC) 0-12 hours from measurements taken at at 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14 in response to all doses administered (see Outcome Measure #29).

    All AUC FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment [ Time Frame: 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 on FEV1 Area under the curve (AUC) 12-24 hours was calculated from measurements taken at 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14.

    AUC FEV1 was measured in response to all doses administered (see Outcome Measure #30). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment [ Time Frame: Days 1 and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 at 12 hours was measured on days 1 and 14.

    FEV1 was measured in response to all doses administered (see Outcome Measure #31). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment [ Time Frame: Days 1, 7, and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time.

    Percentage of the maximal response of NVA237 doses on Peak FEV1 was measured on days 1, 7 and 14 of treatment.

    Peak FEV1 was measured in response to all doses administered (see Outcome Measure #32). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.


  • Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 [ Time Frame: Days 1, 7 and 14 ] [ Designated as safety issue: No ]

    Percentage of the maximal response of NVA237 Doses on Trough Forced Vital Capacity (FVC) on Days 1, 7 and 14. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Trough FVC was assessed via spirometry. (see Outcome Measure #33).

    Trough FVC is defined as the mean of the FVC values measured at 23 hours 15 mins and 23 hours 45 mins post-dose.


  • Mean Daily Use of Rescue Medication by Treatment at Different Time Points [ Time Frame: Baseline, Weeks 1, 2, 3 and 4 ] [ Designated as safety issue: No ]
    Mean daily use of rescue medication by treatment and time points. Baseline was defined as the average of the total number of puffs of rescue medication during the week prior to treatment start, divided by the total number of days with non-missing rescue data during that week, then puffs were counted during weeks 1, 2, 3 and 4 postdose.


Other Outcome Measures:
  • Trough Forced Expiratory Volume in One Second by Treatment at Day 28 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards.

    Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values.


  • Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment [ Time Frame: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards.

    FEV1 Area Under the Curve (AUC) measurements were taken at 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.


  • Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) [ Time Frame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards.

    FEV1 Area Under the Curve (AUC) measurements were taken at: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose). FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.


  • Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment [ Time Frame: 12 hours on day 28 ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards.

  • Peak Forced Expiratory Volume in One Second at Day 28 of Treatment [ Time Frame: 25 min , 15 min pre-dose, 5 min, 15 min, 1 , 2 ,3 , 4 , 6 , 8 , 10 hours , 11 hour 55 min and 14 hour post-dose on day 28 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards.

    Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time. Measurements were taken at 25 min , 15 min pre-dose, 5 min, 15 min, 1 , 2 ,3 , 4 , 6 , 8 , 10 hours , 11 hour 55 min and 14 hour post-dose on day 28.


  • Trough Forced Vital Capacity After 28 Days of Treatment [ Time Frame: 23 hours 15 mins and 23 hours 45 mins post-dose on Day 28 ] [ Designated as safety issue: No ]
    Forced Vital Capacity (FVC) after 28 days of treatment. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. Trough FVC was defined as the mean of the FVC values measured at 23 hours 15 mins and 23 hours 45 mins post-dose.

  • Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 [ Time Frame: 23 hours 15 mins and 23 hours 45 mins post-dose on Days 1, 7 and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards.

    Trough FEV1 was measured on Days 1, 7 and 14 of treatment. Trough FEV1 was defined as the mean of the FEV1 values measured at 23 hours 15 mins and 23 hours 45 mins post-dose.


  • Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment [ Time Frame: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards.

    FEV1 Area Under the Curve (AUC) measurements were taken at 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14 of treatment. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.


  • Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment [ Time Frame: 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards.

    FEV1 Area Under the Curve (AUC) measurements were taken at 5 min, 15 min, 1,2,3,4 hours (postdose) on days 1, 7 and 14 of treatment. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.


  • Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 [ Time Frame: at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7 and 14 ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-8 was calculated from measurements taken at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7, and 14. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.

  • Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment [ Time Frame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14 ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses was calculated on FEV1 Area Under the Curve (AUC) 0-12 hours from measurements taken at at 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.

  • Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment [ Time Frame: 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14 ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 on FEV1 Area under the curve (AUC) 12-24 hours was calculated from measurements taken at 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.

  • Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment [ Time Frame: Days 1 and 14 ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 at 12 hours was measured on days 1 and 14.

  • Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment [ Time Frame: Days 1, 7, and 14 ] [ Designated as safety issue: No ]

    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time.

    Percentage of the maximal response of NVA237 doses on Peak FEV1 was measured on days 1, 7 and 14 of treatment.


  • Trough Forced Vital Capacity on Days 1, 7 and 14 [ Time Frame: Days 1, 7 and 14 ] [ Designated as safety issue: No ]

    Trough Forced Vital Capacity (FVC) on Days 1, 7 and 14. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. (see Outcome Measure #23).

    Trough FVC was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values.



Enrollment: 388
Study Start Date: April 2010
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NVA237 12.5 µg q.d.
NVA237 12.5 µg once daily
Drug: NVA237 12.5 µg once daily
NVA237 12.5 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.
Experimental: NVA237 25.0 µg q.d.
NVA237 25.0 µg once daily
Drug: NVA237 25.0 µg once daily
NVA237 25.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.
Experimental: NVA237 12.5 µg b.i.d.
NVA237 12.5 µg twice daily
Drug: NVA237 12.5 µg twice daily
NVA237 12.5 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.
Experimental: NVA237 50.0 µg q.d.
NVA237 50.0 µg once daily
Drug: NVA237 50.0 µg once daily
NVA237 50.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.
Experimental: NVA237 25.0 µg b.i.d.
NVA237 25.0 µg twice daily
Drug: NVA237 25.0 µg twice daily
NVA237 25.0 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.
Experimental: NVA237 100.0 µg q.d.
NVA237 100.0 µg once daily
Drug: NVA237 100.0 µg once daily
NVA237 100.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.
Experimental: NVA237 50.0 µg b.i.d.
NVA237 50.0 µg twice daily
Drug: NVA237 50.0 µg twice daily
NVA237 50.0 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.
Placebo Comparator: Placebo
Placebo to NVA237 once daily
Drug: Placebo to NVA237 once daily
Placebo to NVA237 via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients age 40 years or more
  • Diagnosis of Chronic Obstructive Lung Disease (COPD) (moderate to severe as classified by the Global Initiative for COPD (GOLD) Guidelines, 2008
  • Smoking history of at least 10 pack-years
  • Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) <80% and ≥30% of the predicted normal value
  • Post-bronchodilator FEV1/Forced Vital Capacity (FVC) <0.7
  • Symptomatic patients, according to daily electronic diary data between visit 2 (Day -8) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to visit 3

Exclusion Criteria:

  • Patients who have had a COPD exacerbation requiring systemic corticosteroids and/or antibiotics and/or hospitalization in the 6 weeks prior to the first visit
  • Patients who have had a respiratory tract infection within 4 weeks prior to the first visit
  • Patients with concomitant pulmonary disease
  • Patients with diabetes Type I or uncontrolled diabetes Type II
  • Any patient with lung cancer or a history of lung cancer
  • Patients with a history of certain cardiovascular co-morbid conditions
  • Patients with a history of asthma or a blood eosinophil count >600/mm3 or onset of symptoms prior to 40 years
  • Patients with eczema, known high IgE levels or a known positive skin prick test
  • Patients participating in the active phase of a pulmonary rehabilitation programme
  • Patients contraindicated for the treatment with anticholinergics, long and short-acting beta-2 agonists or sympathomimetic amines
  • Patients with a history of alpha-1 anti-trypsin deficiency
  • Patients on long term oxygen therapy (>15hr per day)
  • Other protocol-defined inclusion/exclusion criteria may apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01119950

  Show 29 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01119950     History of Changes
Other Study ID Numbers: CNVA237A2208, 2009-014038-11
Study First Received: May 5, 2010
Results First Received: January 23, 2013
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
India: Central Drugs Standard Control Organization
Netherlands: Medicines Evaluation Board (MEB)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Romania: National Medicines Agency

Keywords provided by Novartis:
COPD

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 22, 2014