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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

NVA237 12.5 µg once daily

NVA237 25.0 µg once daily

NVA237 12.5 µg twice daily

NVA237 50.0 µg once daily

NVA237 25.0 µg twice daily

NVA237 100.0 µg once daily

NVA237 50.0 µg twice daily

Placebo to NVA237 once daily

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Placebo Comparator

Arm Label

NVA237 12.5 µg q.d.

NVA237 25.0 µg q.d.

NVA237 12.5 µg b.i.d.

NVA237 50.0 µg q.d.

NVA237 25.0 µg b.i.d.

NVA237 100.0 µg q.d.

NVA237 50.0 µg b.i.d.

Placebo

Arm Description

NVA237 12.5 µg once daily

NVA237 25.0 µg once daily

NVA237 12.5 µg twice daily

NVA237 50.0 µg once daily

NVA237 25.0 µg twice daily

NVA237 100.0 µg once daily

NVA237 50.0 µg twice daily

Placebo to NVA237 once daily

Outcomes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

Full Information

NCT ID

NCT01119950

First Posted

May 5, 2010

Last Updated

March 3, 2015

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01119950

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2015

Overall Recruitment Status

Completed

Study Start Date

April 2010 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Obstructive Pulmonary Disease

Keywords

COPD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

388 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NVA237 12.5 µg q.d.

Arm Type

Experimental

Arm Description

NVA237 12.5 µg once daily

Arm Title

NVA237 25.0 µg q.d.

Arm Type

Experimental

Arm Description

NVA237 25.0 µg once daily

Arm Title

NVA237 12.5 µg b.i.d.

Arm Type

Experimental

Arm Description

NVA237 12.5 µg twice daily

Arm Title

NVA237 50.0 µg q.d.

Arm Type

Experimental

Arm Description

NVA237 50.0 µg once daily

Arm Title

NVA237 25.0 µg b.i.d.

Arm Type

Experimental

Arm Description

NVA237 25.0 µg twice daily

Arm Title

NVA237 100.0 µg q.d.

Arm Type

Experimental

Arm Description

NVA237 100.0 µg once daily

Arm Title

NVA237 50.0 µg b.i.d.

Arm Type

Experimental

Arm Description

NVA237 50.0 µg twice daily

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo to NVA237 once daily

Intervention Type

Drug

Intervention Name(s)

NVA237 12.5 µg once daily

Intervention Description

NVA237 12.5 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

Intervention Type

Drug

Intervention Name(s)

NVA237 25.0 µg once daily

Intervention Description

NVA237 25.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

Intervention Type

Drug

Intervention Name(s)

NVA237 12.5 µg twice daily

Intervention Description

NVA237 12.5 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.

Intervention Type

Drug

Intervention Name(s)

NVA237 50.0 µg once daily

Intervention Description

NVA237 50.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

Intervention Type

Drug

Intervention Name(s)

NVA237 25.0 µg twice daily

Intervention Description

NVA237 25.0 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.

Intervention Type

Drug

Intervention Name(s)

NVA237 100.0 µg once daily

Intervention Description

NVA237 100.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

Intervention Type

Drug

Intervention Name(s)

NVA237 50.0 µg twice daily

Intervention Description

NVA237 50.0 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.

Intervention Type

Drug

Intervention Name(s)

Placebo to NVA237 once daily

Intervention Description

Placebo to NVA237 via dry powder inhaler once daily for 28 days during either period 1 or during period 2.

Primary Outcome Measure Information:

Title

Description

Time Frame

Day 28

Secondary Outcome Measure Information:

Title

Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237

Description

Time Frame

day 28

Title

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

Description

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

Title

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

Description

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

Title

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

Description

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.

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

Title

Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment

Description

Time Frame

12 hours on day 28

Title

Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment

Description

Time Frame

day 28

Title

Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment

Description

Time Frame

day 28

Title

Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14

Description

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.

Time Frame

Days 1, 7 and 14

Title

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

Description

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.

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

Title

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

Description

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.

Time Frame

5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14

Title

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

Description

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.

Time Frame

at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7 and 14

Title

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

Description

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.

Time Frame

5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14

Title

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

Description

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.

Time Frame

11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14

Title

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

Description

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.

Time Frame

Days 1 and 14

Title

Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment

Description

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.

Time Frame

Days 1, 7, and 14

Title

Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14

Description

Time Frame

Days 1, 7 and 14

Title

Mean Daily Use of Rescue Medication by Treatment at Different Time Points

Description

Time Frame

Baseline, Weeks 1, 2, 3 and 4

Other Pre-specified Outcome Measures:

Title

Trough Forced Expiratory Volume in One Second by Treatment at Day 28

Description

Time Frame

Day 28

Title

Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment

Description

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.

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

Title

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)

Description

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.

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

Title

Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment

Description

Time Frame

12 hours on day 28

Title

Peak Forced Expiratory Volume in One Second at Day 28 of Treatment

Description

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.

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

Title

Trough Forced Vital Capacity After 28 Days of Treatment

Description

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.

Time Frame

23 hours 15 mins and 23 hours 45 mins post-dose on Day 28

Title

Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14

Description

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.

Time Frame

23 hours 15 mins and 23 hours 45 mins post-dose on Days 1, 7 and 14

Title

Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment

Description

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.

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

Title

Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment

Description

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.

Time Frame

5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14

Title

Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14

Description

Time Frame

at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7 and 14

Title

Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment

Description

Time Frame

5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14

Title

Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment

Description

Time Frame

11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14

Title

Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment

Description

Time Frame

Days 1 and 14

Title

Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment

Description

Time Frame

Days 1, 7, and 14

Title

Trough Forced Vital Capacity on Days 1, 7 and 14

Description

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.

Time Frame

Days 1, 7 and 14

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Anniston

State/Province

Alabama

ZIP/Postal Code

36201

Country

United States

Facility Name

Novartis Investigative Site

City

San Diego

State/Province

California

ZIP/Postal Code

92101

Country

United States

Facility Name

Novartis Investigative Site

City

Torrance

State/Province

California

ZIP/Postal Code

90501

Country

United States

Facility Name

Novartis Investigative Site

City

Denver

State/Province

Colorado

ZIP/Postal Code

80012

Country

United States

Facility Name

Novartis Investigative Site

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68104

Country

United States

Facility Name

Novartis Investigative Site

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19102

Country

United States

Facility Name

Novartis Investigative Site

City

Antwerpen

Country

Belgium

Facility Name

Novartis Investigative Site

City

Genk

Country

Belgium

Facility Name

Novartis Investigative site

City

Jambes

Country

Belgium

Facility Name

Novartis Investigative Site

City

Muenchen

Country

Germany

Facility Name

Novartis Investigative Site

City

Balassagyarmat

Country

Hungary

Facility Name

Novartis Investigative Site

City

Balatonfured

Country

Hungary

Facility Name

Novartis Investigative Site

City

Budapest

Country

Hungary

Facility Name

Novartis Investigative Site

City

Debrecen

Country

Hungary

Facility Name

Novartis Investigative Site

City

Szolnok

Country

Hungary

Facility Name

Novartis Investigative Site

City

Torokbalint

Country

Hungary

Facility Name

Novartis Investigative Site

City

Almelo

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Eindhoven

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Harderwijk

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Heerlen

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Helmond

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Veldhoven

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Zutphen

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Izabelin

Country

Poland

Facility Name

Novartis Investigative Site

City

Lodz

Country

Poland

Facility Name

Novartis Investigative Site

City

Warszawa

Country

Poland

Facility Name

Novartis Investigative Site

City

Alicante

Country

Spain

Facility Name

Novartis Investigative Site

City

La Coruña

Country

Spain

Facility Name

Novartis Investigative Site

City

Ponferrada

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

23217058

Citation

Arievich H, Overend T, Renard D, Gibbs M, Alagappan V, Looby M, Banerji D. A novel model-based approach for dose determination of glycopyrronium bromide in COPD. BMC Pulm Med. 2012 Dec 8;12:74. doi: 10.1186/1471-2466-12-74.

Results Reference

derived

Learn more about this trial

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

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

Chronic Obstructive Pulmonary Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial