Trial Outcomes & Findings for Effect of NVA237 on Exercise Endurance in Patients With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01154127)

NCT ID: NCT01154127

Last Updated: 2012-05-07

Results Overview

SMETT is an exercise procedure where the patient cycles at 80% of the maximum workload (Wmax )value achieved at the Incremental exercise test. During this test, the patient will cycle at a constant load. Exercise endurance time was from commencement of loaded pedaling to stopping exercise. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 108 participants
• Primary outcome timeframe: Day 21
• Results posted on: 2012-05-07

Participant Flow

Participant milestones

Measure	NVA237 Followed by Placebo Period 1: 50 μg NVA237 via NEOHALER inhaler device for 21 days. Period 2: Matching placebo via NEOHALER inhaler device for 21 days The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo Followed by NVA237 Period 1: Matching placebo of NVA237 via NEOHALER inhaler device for 21 days Period 2: 50 μg NVA237 via NEOHALER inhaler device for 21 days. The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Period 1 (21 Days) STARTED	55	53
Period 1 (21 Days) COMPLETED	52	47
Period 1 (21 Days) NOT COMPLETED	3	6
Washout (14 - 28 Days) STARTED	52	47
Washout (14 - 28 Days) COMPLETED	49	47
Washout (14 - 28 Days) NOT COMPLETED	3	0
Period 2 (21 Days) STARTED	49	47
Period 2 (21 Days) COMPLETED	49	46
Period 2 (21 Days) NOT COMPLETED	0	1

Reasons for withdrawal

Measure	NVA237 Followed by Placebo Period 1: 50 μg NVA237 via NEOHALER inhaler device for 21 days. Period 2: Matching placebo via NEOHALER inhaler device for 21 days The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo Followed by NVA237 Period 1: Matching placebo of NVA237 via NEOHALER inhaler device for 21 days Period 2: 50 μg NVA237 via NEOHALER inhaler device for 21 days. The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Period 1 (21 Days) Adverse Event	3	4
Period 1 (21 Days) Withdrawal by Subject	0	2
Washout (14 - 28 Days) Adverse Event	2	0
Washout (14 - 28 Days) Abnormal Test Procedure	1	0
Period 2 (21 Days) Protocol Deviation	0	1

Baseline Characteristics

Effect of NVA237 on Exercise Endurance in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Measure	NVA237 Followed by Placebo n=55 Participants Period 1: 50 μg NVA237 via NEOHALER inhaler device for 21 days. Period 2: Matching placebo via NEOHALER inhaler device for 21 days The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo Followed by NVA237 n=53 Participants Period 1: Matching placebo of NVA237 via NEOHALER inhaler device for 21 days Period 2: 50 μg NVA237 via NEOHALER inhaler device for 21 days. The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Total n=108 Participants Total of all reporting groups
Age Continuous	61.3 years STANDARD_DEVIATION 8.50 • n=5 Participants	59.7 years STANDARD_DEVIATION 8.78 • n=7 Participants	60.5 years STANDARD_DEVIATION 8.64 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	20 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	33 Participants n=7 Participants	63 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 21

Population: Pharmacodynamics (PD) set consisted of participants who completed at least one treatment period, had an evaluable PD assessment on Day 21 of this period and had no major protocol deviation impacting the primary PD assessment.

SMETT is an exercise procedure where the patient cycles at 80% of the maximum workload (Wmax )value achieved at the Incremental exercise test. During this test, the patient will cycle at a constant load. Exercise endurance time was from commencement of loaded pedaling to stopping exercise. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.

Outcome measures

Measure	NVA237 n=96 Participants Participants received NVA237 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo n=96 Participants Participants received Placebo 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Exercise Endurance Time During a Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks (Day 21) of Treatment	505.63 seconds Interval 466.59 to 544.68	416.70 seconds Interval 377.76 to 455.64

SECONDARY outcome

Timeframe: Day 21

Population: Pharmacodynamics (PD) set consisted of participants who completed at least one treatment period, had an evaluable PD assessment on Day 21 of this period and had no major protocol deviation impacting primary the PD assessment.

Isotime is the last matching timepoint in the submaximal exercise tolerance test (SMETT) at which for both periods the patient has a test result. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.

Outcome measures

Measure	NVA237 n=92 Participants Participants received NVA237 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo n=92 Participants Participants received Placebo 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Isotime Inspiratory Capacity (IC) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks of Treatment	2.22 Liters Interval 2.15 to 2.31	2.02 Liters Interval 1.95 to 2.08

SECONDARY outcome

Timeframe: Day 21

Population: Pharmacodynamics (PD) set consisted of participants who completed at least one treatment period, had an evaluable PD assessment on Day 21 of this period and had no major protocol deviation impacting the primary PD assessment. "n" indicates number of participants with observation at each time-point.

IC at peak was observed using spirometry. However, two different methodologies (whole body plethysmography (Bodybox) and spirometry) were used to observe IC at rest.

The analysis of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.

Outcome measures

Measure	NVA237 n=99 Participants Participants received NVA237 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo n=96 Participants Participants received Placebo 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Inspiratory Capacity (IC) at Rest (1 Hour Post Dose) and at Peak (End of Exercise) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks of Treatment IC at peak (Spirometry), Day 21 (n = 93, 90)	2.22 Litres Interval 2.16 to 2.28	2.03 Litres Interval 1.97 to 2.1
Inspiratory Capacity (IC) at Rest (1 Hour Post Dose) and at Peak (End of Exercise) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks of Treatment IC at rest (Bodybox) Day 21 (n= 97, 96)	2.49 Litres Interval 2.4 to 2.59	2.26 Litres Interval 2.17 to 2.35
Inspiratory Capacity (IC) at Rest (1 Hour Post Dose) and at Peak (End of Exercise) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks of Treatment IC at rest (Spirometry), Day 21 (n= 98, 96)	2.39 Litres Interval 2.33 to 2.45	2.17 Litres Interval 2.1 to 2.23

SECONDARY outcome

Timeframe: Day 21

Population: Pharmacodynamics (PD) set consisted of participants who completed at least one treatment period, had an evaluable PD assessment on Day 21 of this period and had no major protocol deviation impacting the primary PD assessment.

FEV1 is the amount of air that can be exhaled in one second. FEV1 was measured with spirometry conducted according to internationally accepted standards.

FVC is the volume of air that can forcibly be blown out after full inspiration and is used in spirometry tests.

The trough effects of Day 1 treatment are derived from values prior to morning dosing on the next treatment day (Day 2 of the corresponding period).

The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.

Outcome measures

Measure	NVA237 n=99 Participants Participants received NVA237 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo n=96 Participants Participants received Placebo 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Peak and Trough (24 h Post Dose) Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1 at peak, Day 21	1.60 Litres Interval 1.56 to 1.64	1.35 Litres Interval 1.31 to 1.39
Peak and Trough (24 h Post Dose) Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1 at trough, Day 21	1.44 Litres Interval 1.4 to 1.48	1.33 Litres Interval 1.29 to 1.37
Peak and Trough (24 h Post Dose) Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC at peak, Day 21	3.37 Litres Interval 3.3 to 3.44	3.00 Litres Interval 2.93 to 3.06
Peak and Trough (24 h Post Dose) Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC at trough, Day 21	3.17 Litres Interval 3.11 to 3.23	2.96 Litres Interval 2.9 to 3.02

SECONDARY outcome

Timeframe: Day 21

Population: Pharmacodynamics (PD) set consisted of participants who completed at least one treatment period, had an evaluable PD assessment on Day 21 of this period and had no major protocol deviation impacting the primary PD assessment. "n" indicates number of participants with observation at each time-point.

Vital Capacity is the amount of air that can be forcibly exhaled from the lungs after a full inhalation. Slow Vital Capacity (SVC) test is performed by having the patient slowly and completely blow out all of the air from their lungs.

Total Lung Capacity (TLC) is the best vital capacity plus residual volume. Whole body plethysmography (Bodybox) was used to measure SVC and TLC. The trough effects of Day 1 treatment are derived from values prior to morning dosing on the next treatment day (Day 2 of the corresponding period).

Outcome measures

Measure	NVA237 n=99 Participants Participants received NVA237 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo n=96 Participants Participants received Placebo 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Slow Vital Capacity (SVC) and Total Lung Capacity (TLC) SVC at trough, Day 21 (n= 98, 96)	3.21 Litres Interval 3.14 to 3.27	3.14 Litres Interval 3.07 to 3.21
Slow Vital Capacity (SVC) and Total Lung Capacity (TLC) SVC at peak, Day 21 (n= 97, 96)	3.40 Litres Interval 3.33 to 3.47	3.14 Litres Interval 3.07 to 3.21
Slow Vital Capacity (SVC) and Total Lung Capacity (TLC) TLC at trough, Day 21 (n= 98, 96)	6.99 Litres Interval 6.88 to 7.09	7.17 Litres Interval 7.07 to 7.28
Slow Vital Capacity (SVC) and Total Lung Capacity (TLC) TLC at peak, Day 21 (n= 97, 96)	6.86 Litres Interval 6.75 to 6.97	7.10 Litres Interval 6.99 to 7.21

SECONDARY outcome

Timeframe: Day 21

Population: Pharmacodynamics (PD) set consisted of participants who completed at least one treatment period, had an evaluable PD assessment on Day 21 of this period and had no major protocol deviation impacting the primary PD assessment.

SGaw is a measure of how hard it is to get air into the lungs, measured by (Sec(-1)*kP). Whole body plethysmography (Bodybox) was used to measure SGaw.

The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.

Outcome measures

Measure	NVA237 n=99 Participants Participants received NVA237 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo n=96 Participants Participants received Placebo 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Specific Airways Conductance (SGaw) SGaw at trough, Day 21 (n= 98, 96)	0.48 litres/(Second*kpa); kpa = kilopascal Interval 0.45 to 0.51	0.40 litres/(Second*kpa); kpa = kilopascal Interval 0.38 to 0.43
Specific Airways Conductance (SGaw) SGaw at peak, Day 21 (n= 97, 96)	0.66 litres/(Second*kpa); kpa = kilopascal Interval 0.63 to 0.7	0.42 litres/(Second*kpa); kpa = kilopascal Interval 0.39 to 0.46

SECONDARY outcome

Timeframe: Day 21

Population: Pharmacodynamics (PD) set consisted of participants who completed at least one treatment period, had an evaluable PD assessment on Day 21 of this period and had no major protocol deviation impacting the primary PD assessment.

The Borg CR10 Scale consists of 12-point score that the patients pointed to so as to indicate their level of dyspnea before and during exercise testing (where 0 indicates no breathlessness at all and 12 indicates maximum breathlessness).

A reduction in this score indicates an improvement. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.

Outcome measures

Measure	NVA237 n=93 Participants Participants received NVA237 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo n=93 Participants Participants received Placebo 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Exertional Dyspnea (Borg CR10 Scale) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks Treatment	5.64 units on a scale Interval 5.05 to 6.23	6.80 units on a scale Interval 6.2 to 7.39

SECONDARY outcome

Timeframe: Day 21

Population: Pharmacodynamics (PD) set consisted of participants who completed at least one treatment period, had an evaluable PD assessment on Day 21 of this period and had no major protocol deviation impacting the primary PD assessment.

The modified Borg CR10 Scale consists of 12-point score that the patients pointed to so as to indicate their level of leg discomfort before and during exercise testing (where 0 indicates no breathlessness at all and 12 indicates maximum breathlessness).

A reduction in this score indicates an improvement. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.

Outcome measures

Measure	NVA237 n=93 Participants Participants received NVA237 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo n=93 Participants Participants received Placebo 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Leg Discomfort (Borg CR10 Scale) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks Treatment	6.21 units on a scale Interval 5.67 to 6.76	7.05 units on a scale Interval 6.51 to 7.6

SECONDARY outcome

Timeframe: Day 1

Population: Pharmacodynamics (PD) set consisted of participants who completed at least one treatment period, had an evaluable PD assessment on Day 21 of this period and had no major protocol deviation impacting the primary PD assessment.

SMETT is an exercise procedure where the patient cycles at 80% of the maximum workload (Wmax )value achieved at the Incremental exercise test. During this test, the patient will cycle at a constant load. Exercise endurance time was from commencement of loaded pedaling to stopping exercise.

The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.

Outcome measures

Measure	NVA237 n=96 Participants Participants received NVA237 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo n=94 Participants Participants received Placebo 50 μg once daily delivered via the NEOHALER inhaler device device for 3 weeks (21 days). The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Exercise Endurance Time During a Sub-maximal Constant-load Cycle Ergometry Test (SMETT) on Treatment Day 1	490.92 Seconds Interval 458.45 to 523.38	447.78 Seconds Interval 415.09 to 480.48

Adverse Events

NVA237

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	NVA237 n=102 participants at risk Period 1: 50 μg NVA237 via NEOHALER inhaler device for 21 days Period 2: Matching placebo via NEOHALER inhaler device for 21 days The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Placebo n=102 participants at risk Period 1: 50 μg NVA237 via NEOHALER inhaler device for 21 days Period 2: Matching placebo via NEOHALER inhaler device for 21 days The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.98% 1/102 All patients as randomized who received at least one dose of study drug are included in the safety analysis set.	0.00% 0/102 All patients as randomized who received at least one dose of study drug are included in the safety analysis set.

Other adverse events

Adverse event data not reported

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER