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Trial record 26 of 7513 for:    Area Under Curve

NVA237 BID Versus Placebo Twelve-week Efficacy Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01715298
Recruitment Status : Completed
First Posted : October 26, 2012
Results First Posted : March 11, 2015
Last Update Posted : March 11, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease
Interventions Drug: NVA237
Drug: Placebo
Enrollment 432
Recruitment Details  
Pre-assignment Details  
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Period Title: Overall Study
Started 216 216
Full Analysis Set (FAS) 215 [1] 214
Completed 209 205
Not Completed 7 11
Reason Not Completed
Lost to Follow-up             0             2
Patient/guardian decision             7             9
[1]
patients were analyzed according to the treatment to which they were randomized
Arm/Group Title NVA237 Placebo Total
Hide Arm/Group Description NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 216 216 432
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 216 participants 216 participants 432 participants
63.9  (8.55) 64.2  (8.41) 64.1  (8.47)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 216 participants 216 participants 432 participants
Female
88
  40.7%
90
  41.7%
178
  41.2%
Male
128
  59.3%
126
  58.3%
254
  58.8%
1.Primary Outcome
Title Change From Baseline in Standardized Area Under the Curve for Forced Expiratory Volume in One Second Post Dosing
Hide Description

The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is measured at week 12 of treatment. Serial lung function measurements are taken at the following time points following dosing at week 12 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.

The primary endpoint was the change from baseline in FEV1 AUC0-12h following the morning dose at Week 12 (defined as the mean FEV1 change from baseline (CFB) over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. analyzed participants had values at both baseline and the corresponding time frame, i.e. week 12
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 215 213
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.115  (0.0153) -0.008  (0.0153)
2.Secondary Outcome
Title Change From Baseline in Standardized Area Under the Curve (AUC(0-12h)) for Forced Expiratory Volume in One Second Post Dosing
Hide Description

The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is assessed at day 1 of treatment. Serial lung function measurements are taken at the following various time points post dosing at day 1 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.

.The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.

Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 215 213
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.121  (0.0096) 0.003  (0.0096)
3.Secondary Outcome
Title Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing
Hide Description

The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1FEV1) is assessed for different time spans (0-4 h, 4-8 h, 8-12 h) within the overall serial measurement post dosing (FEV1 AUCs Time Spans), at day 1 and at week 12 of treatment. Serial lung function measurements are taken at various the following time points post dosing on day 1 and at week 12 to calculate the FEV1 AUC for these different time spans: .5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.

The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 or week 12, respectively, (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.

Time Frame Day 1 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1and Week 12
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 215 214
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Day 1 AUC 0-4h (n=215,213) 0.154  (0.0088) 0.014  (0.0088)
Week 12 AUC 0-4h (n=215,213) 0.153  (0.0159) 0.004  (0.0159)
Day 1 AUC 4-8h (n=213,209) 0.118  (0.0107) 0.011  (0.0109)
Week 12 AUC 4-8h (n=213,209) 0.107  (0.0159) 0.000  (0.0158)
Day 1 AUC 8-12h (n=212,210) 0.085  (0.0120) -0.021  (0.0120)
Week 12 AUC 8-12h (n=212,210) 0.075  (0.0164) -0.033  (0.0164)
4.Secondary Outcome
Title Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints
Hide Description The Forced Expiratory Volume in one second (FEV1) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed. Time points of the serial lung function measurements are 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The table indicates the percent change from baseline (CFB) in FEV1 and standard deviation in brackets. Where the FEV1 is lower than at baseline, a negative percent value can occur.
Time Frame Day 1 and week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1and Week 12
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 215 214
Mean (Standard Deviation)
Unit of Measure: Percent
FEV1, day 1, 5 min (n=207,202) 4.9  (8.67) -0.3  (7.07)
FEV1, day 1, 15 min (n=209,201) 9.9  (10.05) 0.3  (7.62)
FEV1, day 1, 1 h (n=205,205) 13.9  (11.98) 1.2  (9.05)
FEV1, day 1, 2 h (n=201,205) 16.0  (14.42) 2.5  (9.80)
FEV1, day 1, 4 h (n=199,202) 12.7  (13.39) 2.2  (12.63)
FEV1, day 1, 6h (n=197,197) 10.3  (13.82) 2.2  (11.88)
FEV1, day 1, 8 h (n=200,189) 8.9  (14.43) -0.5  (12.42)
FEV1, day 1, 11 h 55min (n=184,182) 6.6  (13.44) -1.7  (14.03)
FEV1, day 85, -45min (n=184,188) 6.4  (17.61) 1.7  (17.95)
FEV1, day 85, -15min (n=180,185) 9.6  (18.23) 2.7  (17.82)
FEV1, day 85, 5min (n=185,178) 10.4  (18.78) 1.8  (17.22)
FEV1, day 85, 15min (n=186,189) 12.9  (20.00) 2.0  (17.08)
FEV1, day 85, 1h (n=184,187) 15.8  (20.49) 1.6  (17.37)
FEV1, day 85, 2h (n=178,187) 16.0  (20.83) 2.4  (18.52)
FEV1, day 85, 4h (n=179,183) 12.5  (19.72) 3.5  (20.25)
FEV1, day 85, 6h (n=174,172) 9.8  (18.78) 2.5  (20.84)
FEV1, day 85, 8h (n=178,174) 7.8  (18.18) 0.2  (18.86)
FEV1, day 85, 11h 55min (n=171,171) 7.2  (19.39) -2.1  (20.07)
5.Secondary Outcome
Title Mean Trough Forced Expiratory Volume in One Second
Hide Description Mean trough Forced Expiratory Volume in one second (FEV1) is assessed as the arithmetic mean of two FEV1 measurements, conducted within the last hour of a 24 hour period from a morning dose, either that of day 1 or at week 12 of treatment. The data is reported as the change from baseline (CFB), with the baseline being the arithmetic mean of the two pre-dose measurements (-45 min and -15 min) preceding the serial lung function measurements on Day 1
Time Frame Day 1 and week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1and Week 12
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 213 208
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Day 1 0.128  (0.0129) 0.021  (0.0130)
Week 12 0.123  (0.0166) 0.038  (0.0166)
6.Secondary Outcome
Title Change From Baseline in the Health Status Assessed by St. George’s Respiratory Questionnaire
Hide Description The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ is a 50 item scale assessing symptoms, patient activities and impact of the disease. Scores range from 0 to 100 units, with higher scores indicating more limitations. The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically meaningful improvement (MCID) in SGRQ is defined as a decrease of 4 or more units of the SGRQ scale in the total score, as compared to baseline (change from baseline).
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 193 194
Least Squares Mean (Standard Error)
Unit of Measure: Score
-6.4  (1.08) -1.2  (1.06)
7.Secondary Outcome
Title Breathlessness Assessed by Transition Dyspnea Index
Hide Description Breathlessness at week 12 is measured using the interviewer-administered Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the interviewer-administered Baseline Dyspnea Index (BDI). The change from BDI to TDI is assessed, with the TDI total score ranging from -9 to +9 units of the scale. The lower the score, the more deterioration in severity of dyspnea. Patients are considered to have clinically significant improvement (MCID) with the TDI score change versus BDI being equal to or greater than 1.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 190 190
Least Squares Mean (Standard Error)
Unit of Measure: Score
0.95  (0.280) 0.48  (0.277)
8.Secondary Outcome
Title Change From Baseline in Mean Number of Puffs of Rescue Medication Per Day
Hide Description Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the change from baseline in the mean daily number of puffs used per patient over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization (mean number of puffs per day). A negative number indicates a reduction in the mean daily number of puffs of rescue medication.
Time Frame Baseline and week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 208 201
Least Squares Mean (Standard Error)
Unit of Measure: Number of puffs
-1.33  (0.163) -0.80  (0.160)
9.Secondary Outcome
Title Change From Baseline in the Percentage of Days Without Rescue Medication Use
Hide Description Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the change from baseline in the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated as the percentage of days without usage of rescue medication from during the the run-in epoch prior to randomization.
Time Frame Baseline and week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. week 12
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 206 198
Least Squares Mean (Standard Error)
Unit of Measure: percentage of days
11.4  (1.95) 7.0  (1.97)
10.Secondary Outcome
Title Change From Baseline in Daily Symptom Scores
Hide Description Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Symptom scores are calculated as the mean of the combined daily symptom scores (combined from morning and evening scores) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The change from baseline in the least squares mean daily symptom scores over the 12 week treatment period is provided. Where the mean daily symptom score over the 12 week treatment period is lower than the baseline, the result is negative. A negative result indicates an improvement in COPD symptom severity.
Time Frame day 1 to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 208 201
Least Squares Mean (Standard Error)
Unit of Measure: Score
-1.09  (0.103) -0.80  (0.104)
11.Secondary Outcome
Title Change From Baseline in the Percentage of Nights With "no Nighttime Awakenings"
Hide Description Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the morning questionnaire relates to the number of awakenings due to COPD symptoms during the previous night. The answer with the lowest symptom score is “no waking due to symptoms.” A night with "no nighttime awakening" is defined from diary data as any night where the patient did not wake up due to symptoms. The change from baseline in the percentage of nights with “no nighttime awakening” is calculated from the mean percentage of nights with this answer over the 12 week treatment period, with the baseline being The baseline is calculated from the run-in epoch prior to randomization.
Time Frame Day 1 and week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 208 200
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of nights
13.1  (1.52) 9.2  (1.54)
12.Secondary Outcome
Title Change From Baseline in the Percentage of Days With "no Daytime Symptoms"
Hide Description Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. A day with "no daytime symptoms" is defined from diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum, and no feeling of breathlessness (other than when running) during the past approximately 12 hours in the evening questionnaire. The change from baseline in the percentage of days with “no daytime symptoms” is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline being. The baseline is calculated from the run-in epoch prior to randomization.
Time Frame Day 1 to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 207 195
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of days
3.6  (1.17) 2.6  (1.18)
13.Secondary Outcome
Title Change From Baseline in Percentage of "Days Able to Perform Usual Daily Activities"
Hide Description Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the evening questionnaire relates to the impact of COPD symptoms on the performance of usual daily activities (“Did your respiratory symptoms stop you performing your usual daily activities today“). The answer with the lowest symptom score is “not at all.” A "day able to perform usual daily activities" is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms. The change from baseline in the percentage of “days able to perform usual daily activities” is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline beingThe baseline is calculated from the run-in epoch prior to randomization.
Time Frame Day 1 to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 207 195
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of days
5.2  (1.61) 0.9  (1.65)
14.Secondary Outcome
Title Change From Baseline in Forced Vital Capacity at All Individual Timepoints
Hide Description The Forced Vital Capacity (FVC)assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed. Serial lung function measurements are taken at the following time points following dosing on Day 1 and at week 12: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. For week 12 (day 85), the pre-dose measurements (-45 min and -15 min) and the trough measurements (23:15 h and 23:45 h post-dose) are included. The endpoints are the change from baseline in FVC following the morning dose on Day 1 and at Week 12. Where the FVC at any one timepoint is smaller than at baseline, a negative value can occur.
Time Frame Day 1 and week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 215 214
Least Squares Mean (Standard Error)
Unit of Measure: Liters
FVC, day 1, 5 min (n=214,211) 0.120  (0.0129) -0.014  (0.0131)
FVC, day 1, 15 min (n=214,213) 0.233  (0.0155) 0.005  (0.0157)
FVC, day 1, 1 h (n=215,211) 0.304  (0.0175) 0.041  (0.0176)
FVC, day 1, 2 h (n=211,211) 0.322  (0.0193) 0.060  (0.0191)
FVC, day 1, 4 h (n=209,208) 0.247  (0.0196) 0.048  (0.0195)
FVC, day 1, 6 h (n=208,205) 0.225  (0.0219) 0.051  (0.0220)
FVC, day 1, 8 h (n=209,205) 0.200  (0.0228) -0.002  (0.0232)
FVC, day 1, 11 h 55min (n=203,202) 0.147  (0.0242) -0.017  (0.0243)
FVC, day 85, -45 min (n=207,204) 0.123  (0.0248) 0.008  (0.0246)
FVC, day 85, -15 min (n=208,204) 0.146  (0.0241) 0.010  (0.0239)
FVC, day 85, 5 min (n=214,211) 0.177  (0.0247) 0.001  (0.0251)
FVC, day 85, 15 min (n=214,213) 0.219  (0.0261) -0.003  (0.0259)
FVC, day 85, 1 hr (n=215,211) 0.267  (0.0261) 0.010  (0.0260)
FVC, day 85, 2 hr (n=211,211) 0.275  (0.0277) 0.024  (0.0271)
FVC, day 85, 4 hr (n=209,208) 0.204  (0.0281) 0.035  (0.0278)
FVC, day 85, 6 hr (n=208,205) 0.185  (0.0278) 0.016  (0.0278)
FVC, day 85, 8 hr (n=209,205) 0.152  (0.0264) -0.015  (0.0266)
FVC, day 85, 11 hr 55min (n=203,202) 0.135  (0.0290) -0.045  (0.0288)
FVC, day 85, 23 hr 15min (n=210,204) 0.207  (0.0289) 0.066  (0.0284)
FVC, day 85, 23 hr 45min (n=213,208) 0.228  (0.0292) 0.095  (0.0290)
15.Secondary Outcome
Title Change From Baseline in Mean Trough Forced Vital Capacity
Hide Description Mean trough Forced Vital Capacity (FVC) is assessed as the arithmetic mean of two FVC measurements, conducted within the last hour of a 24 hours period from a morning dose, either that of day 1 or at week 12 of treatment (23:15 h and 23:45 h assessments). The endpoints are the change from baseline in trough FVC on Day 1 and at Week 12, with the mean of the -45 min and -15 min measurements on Day 1 as the baseline.
Time Frame Day 1 and week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description:
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 213 208
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Day 1 0.249  (0.0225) 0.078  (0.0227)
Week 12 0.210  (0.0277) 0.080  (0.0276)
16.Secondary Outcome
Title Change From Baseline in Morning and Nighttime Symptom Scores
Hide Description Patients are reporting morning and nighttime symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Morning and nighttime symptoms scores for each patient over 12 weeks are reported and analyzed. Symptom scores are calculated as the mean of the symptom scores (morning symptom scores or nighttime symptom scores, respectively) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The outcome is calculated as the change from baseline in the morning and nighttime symptom scores, respectively. A negative number indicates a reduction in the symptom severity and is owed to the calculation of the change from baseline.
Time Frame Day 1 to week 12
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The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
Arm/Group Title NVA237 Placebo
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NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
Overall Number of Participants Analyzed 215 214
Least Squares Mean (Standard Error)
Unit of Measure: Score
Daytime total symptom score (n=207,195) -0.86  (0.097) -0.61  (0.100)
Nighttime total symptom score (n=208,200) -1.03  (0.101) -0.76  (0.102)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title NVA237 Placebo
Hide Arm/Group Description NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
All-Cause Mortality
NVA237 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
NVA237 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   9/216 (4.17%)   5/214 (2.34%) 
Cardiac disorders     
ACUTE MYOCARDIAL INFARCTION  1  1/216 (0.46%)  0/214 (0.00%) 
ANGINA PECTORIS  1  1/216 (0.46%)  0/214 (0.00%) 
Infections and infestations     
CELLULITIS  1  1/216 (0.46%)  0/214 (0.00%) 
HERPES SIMPLEX  1  1/216 (0.46%)  0/214 (0.00%) 
OPHTHALMIC HERPES ZOSTER  1  1/216 (0.46%)  0/214 (0.00%) 
PNEUMONIA  1  1/216 (0.46%)  0/214 (0.00%) 
Injury, poisoning and procedural complications     
SPINAL COMPRESSION FRACTURE  1  0/216 (0.00%)  1/214 (0.47%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
METASTATIC SQUAMOUS CELL CARCINOMA  1  1/216 (0.46%)  0/214 (0.00%) 
SQUAMOUS CELL CARCINOMA OF THE VULVA  1  1/216 (0.46%)  0/214 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  3/216 (1.39%)  3/214 (1.40%) 
HAEMOPTYSIS  1  0/216 (0.00%)  1/214 (0.47%) 
PULMONARY MASS  1  0/216 (0.00%)  1/214 (0.47%) 
RESPIRATORY FAILURE  1  1/216 (0.46%)  0/214 (0.00%) 
Vascular disorders     
PERIPHERAL ARTERY ANEURYSM  1  1/216 (0.46%)  0/214 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.9%
NVA237 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   88/216 (40.74%)   81/214 (37.85%) 
Eye disorders     
VISION BLURRED  1  1/216 (0.46%)  2/214 (0.93%) 
Gastrointestinal disorders     
CONSTIPATION  1  1/216 (0.46%)  2/214 (0.93%) 
DIARRHOEA  1  2/216 (0.93%)  3/214 (1.40%) 
DRY MOUTH  1  2/216 (0.93%)  1/214 (0.47%) 
NAUSEA  1  2/216 (0.93%)  0/214 (0.00%) 
General disorders     
FATIGUE  1  1/216 (0.46%)  2/214 (0.93%) 
OEDEMA PERIPHERAL  1  1/216 (0.46%)  3/214 (1.40%) 
PAIN  1  2/216 (0.93%)  0/214 (0.00%) 
Infections and infestations     
BRONCHITIS  1  0/216 (0.00%)  4/214 (1.87%) 
CANDIDA INFECTION  1  3/216 (1.39%)  0/214 (0.00%) 
CELLULITIS  1  2/216 (0.93%)  0/214 (0.00%) 
GASTROENTERITIS  1  2/216 (0.93%)  0/214 (0.00%) 
GASTROENTERITIS VIRAL  1  2/216 (0.93%)  3/214 (1.40%) 
NASOPHARYNGITIS  1  5/216 (2.31%)  2/214 (0.93%) 
ORAL CANDIDIASIS  1  2/216 (0.93%)  0/214 (0.00%) 
SINUSITIS  1  3/216 (1.39%)  2/214 (0.93%) 
UPPER RESPIRATORY TRACT INFECTION  1  7/216 (3.24%)  3/214 (1.40%) 
URINARY TRACT INFECTION  1  3/216 (1.39%)  3/214 (1.40%) 
VIRAL UPPER RESPIRATORY TRACT INFECTION  1  2/216 (0.93%)  3/214 (1.40%) 
Injury, poisoning and procedural complications     
ACCIDENTAL OVERDOSE  1  2/216 (0.93%)  1/214 (0.47%) 
FALL  1  1/216 (0.46%)  2/214 (0.93%) 
MUSCLE STRAIN  1  1/216 (0.46%)  2/214 (0.93%) 
PROCEDURAL PAIN  1  2/216 (0.93%)  1/214 (0.47%) 
Investigations     
BLOOD PRESSURE INCREASED  1  2/216 (0.93%)  0/214 (0.00%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  2/216 (0.93%)  0/214 (0.00%) 
ARTHRITIS  1  2/216 (0.93%)  0/214 (0.00%) 
BACK PAIN  1  5/216 (2.31%)  1/214 (0.47%) 
PAIN IN EXTREMITY  1  2/216 (0.93%)  0/214 (0.00%) 
Nervous system disorders     
DIZZINESS  1  3/216 (1.39%)  2/214 (0.93%) 
HEADACHE  1  2/216 (0.93%)  7/214 (3.27%) 
Respiratory, thoracic and mediastinal disorders     
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  43/216 (19.91%)  43/214 (20.09%) 
COUGH  1  6/216 (2.78%)  6/214 (2.80%) 
DYSPNOEA  1  3/216 (1.39%)  3/214 (1.40%) 
NASAL CONGESTION  1  0/216 (0.00%)  5/214 (2.34%) 
OROPHARYNGEAL PAIN  1  5/216 (2.31%)  1/214 (0.47%) 
RESPIRATORY TRACT CONGESTION  1  2/216 (0.93%)  1/214 (0.47%) 
RHINITIS ALLERGIC  1  3/216 (1.39%)  0/214 (0.00%) 
RHINORRHOEA  1  1/216 (0.46%)  3/214 (1.40%) 
Skin and subcutaneous tissue disorders     
RASH  1  1/216 (0.46%)  2/214 (0.93%) 
Vascular disorders     
HYPERTENSION  1  2/216 (0.93%)  2/214 (0.93%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Results Point of Contact
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Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
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Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01715298     History of Changes
Other Study ID Numbers: CNVA237A2318
First Submitted: October 24, 2012
First Posted: October 26, 2012
Results First Submitted: December 17, 2014
Results First Posted: March 11, 2015
Last Update Posted: March 11, 2015