GLOW4: Long Term Safety and Tolerability of NVA237 Versus Tiotropium in Japanese Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01119937
• Collaborator: (none)
• Enrollment: 211
• Locations: 40
• Arms: 2
• Patients Per Site: 5.3

Study Details

Study Description

Brief Summary

This is a 52-week, multi-center, randomized, open label, parallel group study to assess the long term safety and tolerability of once-daily NVA237, using tiotropium as an active control, in Japanese patients with moderate to severe chronic obstructive pulmonary disease (COPD) .

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: NVA237; Drug: Tiotropium	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 211 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 52-week Treatment, Multi-center, Randomized, Open Label, Parallel Group Study to Assess the Long Term Safety and Tolerability of NVA237 (50µg o.d.) Using Tiotropium (18µg o.d.) as an Active Control in Japanese Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NVA237 50µg once daily	Drug: NVA237; 50µg capsules for inhalation, delivered via a single dose dry powder inhaler (Concept 1®)
Experimental: Tiotropium 18µg once daily	Drug: Tiotropium; 18µg capsules for inhalation, delivered via HandiHaler®

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events, Serious Adverse Events or Death [52 weeks]

   Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.

Secondary Outcome Measures

1. Change in Pre-dose FEV1 From Baseline [Weeks 12, 24, 36 and 52]

   Pre-dose FEV1 is defined as the average of the measurements at 45 and 15 minutes pre-dose.

2. Change in Pre-dose FVC From Baseline [Weeks 12, 24, 36 and 52]

   Pre-dose FVC is defined as the average of the measurements at 45 and 15 minutes pre-dose.

3. Time From Randomization Until the Start of the First Moderate or Severe COPD Exacerbation [52 weeks]

   Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required. Participants who withdraw from the study and do not experience a moderate or severe exacerbation are censored at the date of withdrawal. Participants who complete the study and do not experience a moderate or severe exacerbation are censored at the completion visit date.

4. Number of Patients With Moderate or Severe COPD Exacerbations [52 weeks]

   Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required.

5. Change in St. George Respiratory Questionnaire From Baseline [Weeks 12, 24, 36, 52]

   SGRQ is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life.

6. Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Over the Whole Treatment Period [52 weeks]

   Patients recorded rescue medication use in a paper patient diary. If a patient required the use of salbutamol as rescue medication due to an increase in COPD symptoms, the number of inhalations (puffs) taken was recorded in the patient diary.

7. Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period [52 weeks]

   Clinically notable hematology values were: hemoglobin - male <11.5g/dL, female <9.5 g/dL; hematocrit - male <37%, female <32%; white cell count - <2800µL or >16000µL; platelets - <7.5 10*4/µL or >70.0 10*4/µL

8. Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period [52 weeks]

   Clinically notable biochemistry values were: total protein - <4.0 g/dL or >9.5 g/dL; albumin <2.5 g/dL; bilirubin (total) >1.9 mg/dL; BUN >27 mg/dL; creatinine >1.99 mg/dL; AST >3 x ULN U/L; ALT >3 x ULN U/L; ALP >3 x ULN U/L; y-GTP >3 x ULN U/L; sodium <125 mEq/L or >160 mEq/L; potassium <3.0 mEq/L or >6.0 mEq/L; glucose <51.0 mg/dL or >180.0 mg/dL

9. Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period [52 weeks]

   Clinically notable vital sign values were: pulse rate - low, <40 bpm or <=50 bpm and decrease from baseline >=15bpm; pulse rate high, >130 bpm or >=120bpm and increase from baseline >=15 bpm. Systolic blood pressure - low, <75 mmHg or <=90 mmHg and decrease from baseline >=20 mmHg; high, >200 mmHg or >=180 mmHg and increase from baseline >=20 mmHg. Diastolic blood pressure - low, <40 mmHg or <=50 mmHg and decrease from baseline >=15 mmHg; high, >115 mmHg or >=105 mmHg and increase from baseline >=15 mmHg.

10. Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period [52 weeks]

    Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with moderate to severe stable COPD (Stage II or Stage III) according to the Gold Guideline 2008.

• Current or ex-smokers who have a smoking history of at least 10 pack years.

• Patients with a post-bronchodilator FEV1 ≥30% and < 80% of the predicted normal, and postbronchodilator FEV1/FVC < 0.7 at Visit 2 (day -7)

Exclusion Criteria:

• Pregnant women or nursing mothers or women of child-bearing potential not using an acceptable method of contraception

• Patients requiring long term oxygen therapy

• Patients who have had a lower respiratory tract infection within 6 weeks prior to Visit 1

• Patients with concomitant pulmonary disease

• Patients with a history of asthma

• Any patient with lung cancer or a history of lung cancer

• Patients with a history of certain cardiovascular comorbid conditions

• Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency

• Patients in the active phase of a supervised pulmonary rehabilitation program

• Patients contraindicated for tiotropium or ipratropium treatment or who have shown an untoward reaction to inhaled anticholinergic agents

• Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Iizuka	Fukuoka	Japan	820-8505
2	Novartis Investigative Site	Kitakyushu	Fukuoka	Japan	802-0083
3	Novartis Investigative Site	Kitakyushu	Fukuoka	Japan	820-0052
4	Novartis Investigative Site	Kurume	Fukuoka	Japan	830-0011
5	Novartis Investigative Site	Onojo	Fukuoka	Japan	816-0931
6	Novartis Investigative Site	Yanagawa	Fukuoka	Japan	832-0059
7	Novartis Investigative Site	Asahikawa	Hokkaido	Japan	070-8644
8	Novartis Investigative Site	Obihiro	Hokkaido	Japan	080-0805
9	Novartis Investigative Site	Sapporo	Hokkaido	Japan	060-8648
10	Novartis Investigative Site	Himeji-city	Hyogo	Japan	672-8064
11	Novartis Investigative Site	Takarazuka	Hyogo	Japan	665-0827
12	Novartis Investigative Site	Yabu	Hyogo	Japan	667-8555
13	Novartis Investigative Site	Inashiki-gun	Ibaraki	Japan	300-0395
14	Novartis Investigative Site	Naka-gun	Ibaraki	Japan	319-1113
15	Novartis Investigative Site	Sashima-gun	Ibaraki	Japan	306-0433
16	Novartis Investigative Site	Morioka	Iwate	Japan	020-0055
17	Novartis Investigative Site	Kawasaki	Kanagawa	Japan	210-0852
18	Novartis Investigative Site	Yokohama	Kanagawa	Japan	232-0021
19	Novartis Investigative Site	Yokohama	Kanagawa	Japan	236-0051
20	Novartis Investigative Site	Uji	Kyoto	Japan	611-0042
21	Novartis Investigative Site	Matsusaka-city	Mie	Japan	515-8544
22	Novartis Investigative Site	Sendai	Miyagi	Japan	981-8563
23	Novartis Investigative Site	Nagaoka-City	Niigata	Japan	940-2085
24	Novartis Investigative Site	Nagaoka	Niigata	Japan	940-8653
25	Novartis Investigative Site	Kasaoka	Okayama	Japan	714-0081
26	Novartis Investigative Site	Tsuyama	Okayama	Japan	708-0841
27	Novartis Investigative Site	Osakasayama	Osaka	Japan	589-0022
28	Novartis Investigative Site	Sakai	Osaka	Japan	591-8555
29	Novartis Investigative Site	Takatsuki	Osaka	Japan	569-1096
30	Novartis Investigative Site	Shimotsuka-gun	Tochigi	Japan	321-0293
31	Novartis Investigative Site	Bunkyo-ku	Tokyo	Japan	113-8431
32	Novartis Investigative Site	Nakano-ku	Tokyo	Japan	164-0012
33	Novartis Investigative Site	Ohta-ku	Tokyo	Japan	140-0063
34	Novartis Investigative Site	Yamagata city	Yamagata	Japan	990-8533
35	Novartis Investigative Site	Ube	Yamaguchi	Japan	755-0241
36	Novartis Investigative Site	Fukuoka		Japan	812-0033
37	Novartis Investigative Site	Kochi		Japan	780-8077
38	Novartis Investigative Site	Osaka		Japan	530-0012
39	Novartis Investigative Site	Osaka		Japan	545-8586
40	Novartis Investigative Site	Saitama		Japan	337-0012

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01119937
• Other Study ID Numbers: CNVA237A1302
• First Posted: May 10, 2010
• Last Update Posted: Jan 18, 2013
• Last Verified: Nov 1, 2012

• Keywords provided by Novartis Pharmaceuticals: COPD; NVA237
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Glycopyrrolate; Tiotropium Bromide

Study Results

Participant Flow

Pre-assignment Detail	211 participants entered screening. 163 participants entered treatment.

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Period Title: Overall Study
STARTED	123	40
COMPLETED	104	33
NOT COMPLETED	19	7

Baseline Characteristics

Arm/Group Title	NVA237	Tiotropium	Total
Arm/Group Description	50µg once daily	18µg once daily	Total of all reporting groups
Overall Participants	123	40	163
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.4 (7.29)	69.4 (7.48)	68.7 (7.32)
Sex: Female, Male (Count of Participants)
Female	2 1.6%	2 5%	4 2.5%
Male	121 98.4%	38 95%	159 97.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events, Serious Adverse Events or Death
Description	Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least one dose of study drug

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	123	40
Adverse events	102 82.9%	33 82.5%
Serious adverse events	16 13%	6 15%
Death	0 0%	0 0%

2. Secondary Outcome

Title	Change in Pre-dose FEV1 From Baseline
Description	Pre-dose FEV1 is defined as the average of the measurements at 45 and 15 minutes pre-dose.
Time Frame	Weeks 12, 24, 36 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug. Only participants with measurements at both baseline and the specified timepoint were included in the analysis for the specific timepoint.

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	110	37
Week 12	0.101 (0.1455)	0.173 (0.1976)
Week 24	0.094 (0.1614)	0.144 (0.1435)
Week 36 (n = 106, 36)	0.084 (0.1558)	0.112 (0.2200)
Week 52 (n = 103, 33)	0.068 (0.1829)	0.127 (0.2566)

3. Secondary Outcome

Title	Change in Pre-dose FVC From Baseline
Description	Pre-dose FVC is defined as the average of the measurements at 45 and 15 minutes pre-dose.
Time Frame	Weeks 12, 24, 36 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug. Only participants with measurements at both baseline and the specified timepoint were included in the analysis for the specific timepoint.

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	110	37
Week 12	0.221 (0.3057)	0.220 (0.3029)
Week 24	0.218 (0.2798)	0.179 (0.2285)
Week 36 (n = 106, 36)	0.208 (0.3204)	0.146 (0.2547)
Week 52 (n = 103, 33)	0.195 (0.3739)	0.126 (0.2889)

4. Secondary Outcome

Title	Time From Randomization Until the Start of the First Moderate or Severe COPD Exacerbation
Description	Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required. Participants who withdraw from the study and do not experience a moderate or severe exacerbation are censored at the date of withdrawal. Participants who complete the study and do not experience a moderate or severe exacerbation are censored at the completion visit date.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	123	40
Number [days]	362	359

5. Secondary Outcome

Title	Number of Patients With Moderate or Severe COPD Exacerbations
Description	Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	123	40
0 exacerbations	99 80.5%	31 77.5%
1 exacerbation	17 13.8%	5 12.5%
2 exacerbations	5 4.1%	3 7.5%
3 exacerbations	1 0.8%	0 0%
> = 4 exacerbations	1 0.8%	1 2.5%

6. Secondary Outcome

Title	Change in St. George Respiratory Questionnaire From Baseline
Description	SGRQ is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life.
Time Frame	Weeks 12, 24, 36, 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug. Only participants with measurements at both baseline and the specified timepoint were included in the analysis for the specific timepoint.

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	121	40
Week 12	-2.57 (8.506)	-2.31 (13.654)
Week 24	-1.77 (9.466)	-3.24 (12.908)
Week 36	-2.54 (9.614)	-0.93 (14.214)
Week 52	-2.68 (10.505)	0.36 (15.389)

7. Secondary Outcome

Title	Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Over the Whole Treatment Period
Description	Patients recorded rescue medication use in a paper patient diary. If a patient required the use of salbutamol as rescue medication due to an increase in COPD symptoms, the number of inhalations (puffs) taken was recorded in the patient diary.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population - included all randomized patients who received at least one dose of study drug

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	123	40
Mean (Standard Deviation) [change in puffs]	-0.16 (1.039)	-0.27 (0.859)

8. Secondary Outcome

Title	Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period
Description	Clinically notable hematology values were: hemoglobin - male <11.5g/dL, female <9.5 g/dL; hematocrit - male <37%, female <32%; white cell count - <2800µL or >16000µL; platelets - <7.5 10*4/µL or >70.0 10*4/µL
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least one dose of study drug. Only participants with the required measurements were included for each specific value.

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	123	40
Hemoglobin - male (n = 121, 38)	3 2.4%	2 5%
Hemoglobin - female (n = 121, 38)	0 0%	0 0%
Hematocrit - male (n = 121, 38)	3 2.4%	4 10%
Hematocrit - female (n = 121, 38)	0 0%	0 0%
White cell count - <2800/µL	0 0%	1 2.5%
White cell count - >16000/µL	0 0%	0 0%
Platelets - <7.5 10*4/µL	1 0.8%	0 0%
Platelets - >70.0 10*4/µL	0 0%	0 0%

9. Secondary Outcome

Title	Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period
Description	Clinically notable biochemistry values were: total protein - <4.0 g/dL or >9.5 g/dL; albumin <2.5 g/dL; bilirubin (total) >1.9 mg/dL; BUN >27 mg/dL; creatinine >1.99 mg/dL; AST >3 x ULN U/L; ALT >3 x ULN U/L; ALP >3 x ULN U/L; y-GTP >3 x ULN U/L; sodium <125 mEq/L or >160 mEq/L; potassium <3.0 mEq/L or >6.0 mEq/L; glucose <51.0 mg/dL or >180.0 mg/dL
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least one dose of study drug

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	123	40
Total protein - <4.0 g/dL	0 0%	0 0%
Total protein - >9.5 g/dL	0 0%	0 0%
Albumin - <2.5 g/dL	0 0%	0 0%
Bilirubin (total) - >1.9 mg/dL	2 1.6%	0 0%
BUN - >27 mg/dL	3 2.4%	0 0%
Creatinine - >1.99 mg/dL	0 0%	0 0%
AST - >3 x ULN U/L	1 0.8%	0 0%
ALT - >3 x ULN U/L	0 0%	0 0%
ALP - >3 x ULN U/L	0 0%	1 2.5%
Y-GTP - >3 x ULN U/L	5 4.1%	4 10%
Sodium - <125 mEq/L	0 0%	0 0%
Sodium - >160 mEq/L	0 0%	0 0%
Potassium - <3.0 mEq/L	1 0.8%	0 0%
Potassium - >6.0 mEq/L	0 0%	0 0%
Glucose - <51.0 mg/dL	0 0%	0 0%
Glucose - >180.0 mg/dL	11 8.9%	3 7.5%

10. Secondary Outcome

Title	Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period
Description	Clinically notable vital sign values were: pulse rate - low, <40 bpm or <=50 bpm and decrease from baseline >=15bpm; pulse rate high, >130 bpm or >=120bpm and increase from baseline >=15 bpm. Systolic blood pressure - low, <75 mmHg or <=90 mmHg and decrease from baseline >=20 mmHg; high, >200 mmHg or >=180 mmHg and increase from baseline >=20 mmHg. Diastolic blood pressure - low, <40 mmHg or <=50 mmHg and decrease from baseline >=15 mmHg; high, >115 mmHg or >=105 mmHg and increase from baseline >=15 mmHg.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least one dose of study drug

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	123	40
Pulse rate - low	0 0%	1 2.5%
Pulse rate - high	0 0%	0 0%
Pulse rate - low or high	0 0%	1 2.5%
Systolic blood pressure - low	0 0%	0 0%
Systolic blood pressure - high	1 0.8%	0 0%
Systolic blood pressure - low or high	1 0.8%	0 0%
Diastolic blood pressure - low	1 0.8%	0 0%
Diastolic blood pressure - high	2 1.6%	0 0%
Diastolic blood pressure - low or high	3 2.4%	0 0%

11. Secondary Outcome

Title	Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period
Description	Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms).
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least one dose of study drug

Arm/Group Title	NVA237	Tiotropium
Arm/Group Description	50µg once daily	18µg once daily
Measure Participants	123	40
Increase from baseline 30 to 60 ms	6 4.9%	1 2.5%
Increase from baseline >60 ms	2 1.6%	0 0%

Adverse Events

Arm/Group Title	NVA237		Tiotropium
Arm/Group Description	50µg once daily		18µg once daily
All Cause Mortality
	NVA237		Tiotropium
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	NVA237		Tiotropium
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/123 (13%)		6/40 (15%)
Cardiac disorders
Angina unstable	0/123 (0%)		1/40 (2.5%)
Cardiac failure	1/123 (0.8%)		0/40 (0%)
Eye disorders
Cataract	1/123 (0.8%)		0/40 (0%)
Macular hole	1/123 (0.8%)		0/40 (0%)
Gastrointestinal disorders
Intestinal obstruction	1/123 (0.8%)		0/40 (0%)
Hepatobiliary disorders
Bile duct stone	0/123 (0%)		1/40 (2.5%)
Infections and infestations
Bronchitis	1/123 (0.8%)		0/40 (0%)
Bronchopneumonia	1/123 (0.8%)		0/40 (0%)
Diverticulitis	1/123 (0.8%)		0/40 (0%)
Nasopharyngitis	1/123 (0.8%)		0/40 (0%)
Pneumonia	0/123 (0%)		2/40 (5%)
Pneumonia pneumococcal	1/123 (0.8%)		0/40 (0%)
Sepsis	1/123 (0.8%)		0/40 (0%)
Injury, poisoning and procedural complications
Contusion	0/123 (0%)		1/40 (2.5%)
Heat illness	0/123 (0%)		1/40 (2.5%)
Metabolism and nutrition disorders
Diabetes mellitus	1/123 (0.8%)		0/40 (0%)
Musculoskeletal and connective tissue disorders
Polymyalgia rheumatica	1/123 (0.8%)		0/40 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	1/123 (0.8%)		0/40 (0%)
Lung neoplasm malignant	1/123 (0.8%)		1/40 (2.5%)
Nervous system disorders
Loss of consciousness	1/123 (0.8%)		0/40 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/123 (0.8%)		0/40 (0%)
Chronic obstructive pulmonary disease	2/123 (1.6%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	NVA237		Tiotropium
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	83/123 (67.5%)		33/40 (82.5%)
Ear and labyrinth disorders
Meniere's disease	0/123 (0%)		1/40 (2.5%)
Vertigo	2/123 (1.6%)		2/40 (5%)
Eye disorders
Cataract	1/123 (0.8%)		1/40 (2.5%)
Conjunctivitis	1/123 (0.8%)		1/40 (2.5%)
Dry eye	0/123 (0%)		1/40 (2.5%)
Gastrointestinal disorders
Abdominal distension	1/123 (0.8%)		1/40 (2.5%)
Constipation	6/123 (4.9%)		3/40 (7.5%)
Diarrhoea	1/123 (0.8%)		1/40 (2.5%)
Dry mouth	2/123 (1.6%)		2/40 (5%)
Gastric xanthoma	0/123 (0%)		1/40 (2.5%)
Gastritis	1/123 (0.8%)		3/40 (7.5%)
Gastritis atrophic	3/123 (2.4%)		1/40 (2.5%)
Gastrooesophageal reflux disease	5/123 (4.1%)		0/40 (0%)
Gingivitis	2/123 (1.6%)		1/40 (2.5%)
Hiatus hernia	0/123 (0%)		1/40 (2.5%)
Intestinal polyp	1/123 (0.8%)		1/40 (2.5%)
Nausea	1/123 (0.8%)		1/40 (2.5%)
Toothache	1/123 (0.8%)		2/40 (5%)
General disorders
Fatigue	0/123 (0%)		1/40 (2.5%)
Metaplasia	0/123 (0%)		1/40 (2.5%)
Hepatobiliary disorders
Hepatic function abnormal	1/123 (0.8%)		2/40 (5%)
Infections and infestations
Arthritis infective	0/123 (0%)		1/40 (2.5%)
Bronchitis	6/123 (4.9%)		5/40 (12.5%)
Eczema impetiginous	0/123 (0%)		1/40 (2.5%)
Enterocolitis infectious	0/123 (0%)		1/40 (2.5%)
Gastroenteritis	3/123 (2.4%)		1/40 (2.5%)
Gastroenteritis viral	1/123 (0.8%)		1/40 (2.5%)
Helicobacter infection	0/123 (0%)		2/40 (5%)
Herpes zoster	0/123 (0%)		1/40 (2.5%)
Lower respiratory tract infection	3/123 (2.4%)		2/40 (5%)
Nasopharyngitis	37/123 (30.1%)		13/40 (32.5%)
Oral herpes	1/123 (0.8%)		1/40 (2.5%)
Pharyngitis	6/123 (4.9%)		1/40 (2.5%)
Pneumonia	1/123 (0.8%)		2/40 (5%)
Sinusitis	0/123 (0%)		1/40 (2.5%)
Skin candida	0/123 (0%)		1/40 (2.5%)
Tinea infection	0/123 (0%)		1/40 (2.5%)
Upper respiratory tract infection	6/123 (4.9%)		3/40 (7.5%)
Upper respiratory tract infection bacterial	6/123 (4.9%)		2/40 (5%)
Urinary tract infection	1/123 (0.8%)		1/40 (2.5%)
Injury, poisoning and procedural complications
Contusion	3/123 (2.4%)		1/40 (2.5%)
Fall	0/123 (0%)		1/40 (2.5%)
Fractured sacrum	0/123 (0%)		1/40 (2.5%)
Head injury	0/123 (0%)		1/40 (2.5%)
Rib fracture	0/123 (0%)		1/40 (2.5%)
Investigations
Blood creatinine increased	0/123 (0%)		1/40 (2.5%)
Blood potassium increased	0/123 (0%)		1/40 (2.5%)
Blood pressure increased	1/123 (0.8%)		1/40 (2.5%)
Electrocardiogram T wave abnormal	0/123 (0%)		1/40 (2.5%)
Gamma-glutamyltransferase increased	3/123 (2.4%)		0/40 (0%)
Platelet count increased	0/123 (0%)		1/40 (2.5%)
White blood cell count increased	0/123 (0%)		1/40 (2.5%)
Metabolism and nutrition disorders
Diabetes mellitus	3/123 (2.4%)		0/40 (0%)
Gout	1/123 (0.8%)		1/40 (2.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/123 (1.6%)		1/40 (2.5%)
Back pain	6/123 (4.9%)		1/40 (2.5%)
Periarthritis	1/123 (0.8%)		1/40 (2.5%)
Rheumatoid arthritis	0/123 (0%)		1/40 (2.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm	0/123 (0%)		1/40 (2.5%)
Nervous system disorders
Dizziness	1/123 (0.8%)		1/40 (2.5%)
Intracranial aneurysm	0/123 (0%)		1/40 (2.5%)
Lacunar infarction	0/123 (0%)		1/40 (2.5%)
Psychiatric disorders
Depression	0/123 (0%)		1/40 (2.5%)
Insomnia	3/123 (2.4%)		1/40 (2.5%)
Renal and urinary disorders
Dysuria	3/123 (2.4%)		0/40 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/123 (1.6%)		1/40 (2.5%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/123 (0%)		1/40 (2.5%)
Chronic obstructive pulmonary disease	28/123 (22.8%)		13/40 (32.5%)
Dysphonia	6/123 (4.9%)		2/40 (5%)
Haemoptysis	0/123 (0%)		2/40 (5%)
Lower respiratory tract inflammation	1/123 (0.8%)		1/40 (2.5%)
Sputum retention	4/123 (3.3%)		0/40 (0%)
Upper respiratory tract inflammation	4/123 (3.3%)		1/40 (2.5%)
Skin and subcutaneous tissue disorders
Dermal cyst	1/123 (0.8%)		1/40 (2.5%)
Eczema	3/123 (2.4%)		0/40 (0%)
Eczema asteatotic	2/123 (1.6%)		2/40 (5%)
Rash	0/123 (0%)		2/40 (5%)
Xeroderma	0/123 (0%)		1/40 (2.5%)
Vascular disorders
Hypertension	7/123 (5.7%)		5/40 (12.5%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.