Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of Aclidinium Bromide in the Treatment of Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) (LAS-MD-38) (NCT NCT01045161)

NCT ID: NCT01045161

Last Updated: 2017-01-23

Results Overview

Change from baseline in Trough forced expiratory volume in 1 second before the morning dose of aclidinium bromide, Last Observation Carried Forward (LOCF)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 544 participants
• Primary outcome timeframe: Change from baseline (Week 0) to Week 12
• Results posted on: 2017-01-23

Participant Flow

Patient recruitment occurred from December of 2009 to June of 2010 at 112 study sites (110 in the United States and 2 additional sites in Canada).

A total of 544 patients were randomized, with 542 in the Part A Safety population. Of the 454 patients who completed Part A, 448 patients continued into Part B, receiving at least 1 dose of open-label treatment, were included in the Part B Safety Population. Of these patients, 405 had a baseline and postbaseline assessment for the ITT Population.

Participant milestones

Measure	Placebo - Part A Placebo to Aclidinium Bromide 400 μg - Part B Dose matched placebo, twice per day, oral inhalation for 12 weeks of double-blind treatment. After 12 weeks, patients who were on placebo received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.	Aclidinium Bromide 200μg to Aclidinium Bromide 400μg Aclidinium bromide 200 microgram dose, oral inhalation, twice per day for 12 weeks of double-blind treatment. After 12 weeks, patients who were Aclidinium bromide 200 microgram dose, received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.	Aclidinium Bromide 400μg to Aclidinium Bromide 400μg Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 12 weeks of double-blind treatment. After 12 weeks, patients continued to receive Aclidinium bromide, 400 microgram dose as an open-label treatment for an additional 40 weeks
Part A - 12 Weeks Double Blind Treatment STARTED	182	184	178
Part A - 12 Weeks Double Blind Treatment COMPLETED	151	155	148
Part A - 12 Weeks Double Blind Treatment NOT COMPLETED	31	29	30
Part B - 40 Additional Weeks Open Label STARTED	147	154	147
Part B - 40 Additional Weeks Open Label COMPLETED	111	118	115
Part B - 40 Additional Weeks Open Label NOT COMPLETED	36	36	32

Reasons for withdrawal

Measure	Placebo - Part A Placebo to Aclidinium Bromide 400 μg - Part B Dose matched placebo, twice per day, oral inhalation for 12 weeks of double-blind treatment. After 12 weeks, patients who were on placebo received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.	Aclidinium Bromide 200μg to Aclidinium Bromide 400μg Aclidinium bromide 200 microgram dose, oral inhalation, twice per day for 12 weeks of double-blind treatment. After 12 weeks, patients who were Aclidinium bromide 200 microgram dose, received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.	Aclidinium Bromide 400μg to Aclidinium Bromide 400μg Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 12 weeks of double-blind treatment. After 12 weeks, patients continued to receive Aclidinium bromide, 400 microgram dose as an open-label treatment for an additional 40 weeks
Part A - 12 Weeks Double Blind Treatment Withdrawal by Subject	8	12	6
Part A - 12 Weeks Double Blind Treatment Adverse Event	4	3	8
Part A - 12 Weeks Double Blind Treatment Lack of Efficacy	6	3	2
Part A - 12 Weeks Double Blind Treatment COPD Exacerbation	4	1	6
Part A - 12 Weeks Double Blind Treatment Other Reason	3	3	3
Part A - 12 Weeks Double Blind Treatment Protocol Violation	3	4	3
Part A - 12 Weeks Double Blind Treatment Lost to Follow-up	3	3	2
Part B - 40 Additional Weeks Open Label Withdrawal by Subject	10	7	9
Part B - 40 Additional Weeks Open Label Adverse Event	10	10	7
Part B - 40 Additional Weeks Open Label Lack of Efficacy	3	5	5
Part B - 40 Additional Weeks Open Label COPD Exacerbation	1	5	1
Part B - 40 Additional Weeks Open Label Other Reason	4	2	1
Part B - 40 Additional Weeks Open Label Protocol Violation	3	6	3
Part B - 40 Additional Weeks Open Label Lost to Follow-up	5	1	6

Baseline Characteristics

Efficacy, Safety, and Tolerability of Aclidinium Bromide in the Treatment of Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) (LAS-MD-38)

Baseline characteristics by cohort

Measure	Placebo Part A / Placebo to Aclidinium Bromide 400μg Part B n=182 Participants Dose-matched placebo, twice per day, oral inhalation for 12 weeks of double-blind treatment in Part A of the Trial. After week 12 (conclusion of Part A), patients who were on placebo received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.	Aclidinium Bromide(AB) 200μg Part A / AB 200μg to 400μg Part B n=183 Participants Aclidinium bromide 200 microgram dose, oral inhalation, twice per day for 12 weeks of double-blind treatment in Part A of the Trial. After week 12 (conclusion of Part A), patients who were on a double-blind, 200 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at a 400 microgram dose for an additional 40 weeks.	Aclidinium Bromide(AB) 400μg Part A / AB 400μg to 400μg Part B n=177 Participants Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 12 weeks of double-blind treatment in Part A of the Trial. After week 12 (conclusion of Part A), patients who were on a double-blind, 400 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at the same 400 microgram dose for an additional 40 weeks.	Total n=542 Participants Total of all reporting groups
Age, Continuous Part A	61.7 years STANDARD_DEVIATION 9.3 • n=5 Participants	63.4 years STANDARD_DEVIATION 8.5 • n=7 Participants	63.2 years STANDARD_DEVIATION 9.0 • n=5 Participants	62.8 years STANDARD_DEVIATION 8.9 • n=4 Participants
Age, Continuous Part B	61.3 years STANDARD_DEVIATION 9.1 • n=5 Participants	63.8 years STANDARD_DEVIATION 8.2 • n=7 Participants	63.1 years STANDARD_DEVIATION 8.6 • n=5 Participants	62.8 years STANDARD_DEVIATION 8.7 • n=4 Participants
Age, Customized ≥ 40 to < 60 years - Part A	72 participants n=5 Participants	57 participants n=7 Participants	57 participants n=5 Participants	186 participants n=4 Participants
Age, Customized ≥ 60 to < 70 years - Part A	72 participants n=5 Participants	79 participants n=7 Participants	77 participants n=5 Participants	228 participants n=4 Participants
Age, Customized ≥ 70 years - Part A	38 participants n=5 Participants	47 participants n=7 Participants	43 participants n=5 Participants	128 participants n=4 Participants
Age, Customized ≥ 40 to < 60 years - Part B	60 participants n=5 Participants	46 participants n=7 Participants	46 participants n=5 Participants	152 participants n=4 Participants
Age, Customized ≥ 60 to < 70 years - Part B	58 participants n=5 Participants	67 participants n=7 Participants	67 participants n=5 Participants	192 participants n=4 Participants
Age, Customized ≥ 70 years - Part B	29 participants n=5 Participants	41 participants n=7 Participants	34 participants n=5 Participants	104 participants n=4 Participants
Gender Female	82 Participants n=5 Participants	84 Participants n=7 Participants	88 Participants n=5 Participants	254 Participants n=4 Participants
Gender Male	100 Participants n=5 Participants	99 Participants n=7 Participants	89 Participants n=5 Participants	288 Participants n=4 Participants
Region of Enrollment United States	145 participants n=5 Participants	152 participants n=7 Participants	145 participants n=5 Participants	442 participants n=4 Participants
Region of Enrollment Canada	2 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	6 participants n=4 Participants

PRIMARY outcome

Timeframe: Change from baseline (Week 0) to Week 12

Population: Of 544 patients randomized, 542 patients received at least 1 dose of double-blind treatment and were included in the Safety Population. Of these patients, 541 had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the Intent to Treat (ITT) Population.

Change from baseline in Trough forced expiratory volume in 1 second before the morning dose of aclidinium bromide, Last Observation Carried Forward (LOCF)

Outcome measures

Measure	Placebo n=182 Participants Dose-matched placebo twice per day, inhaled for 12 weeks of treatment.	Aclidinium Bromide 200 μg n=182 Participants Aclidinium bromide 200 μg dose twice per day, inhaled for 12 weeks of treatment.	Aclidinium Bromide 400 μg n=177 Participants Inhaled Aclidinium bromide 400 μg twice per day for 12 weeks.
Part A: Morning Predose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	-0.008 L Standard Error 0.015	0.043 L Standard Error 0.015	0.064 L Standard Error 0.016

PRIMARY outcome

Timeframe: Change from baseline (Week 0) to 52 Weeks

Population: A total of 544 patients were randomized, with 542 in the Part A Safety population. Of the 454 patients who completed Part A, 448 patients continued into Part B, receiving at least 1 dose of open-label treatment, were included in the Part B Safety Population. Of these patients, 405 had a baseline and postbaseline assessment for the ITT Population.

Change from Baseline in Morning Pre-dose (trough) Forced Expiratory Volume in 1 Second (FEV1) at Week 52, Lost Observation Carried Forward (LOCF)

Outcome measures

Measure	Placebo n=134 Participants Dose-matched placebo twice per day, inhaled for 12 weeks of treatment.	Aclidinium Bromide 200 μg n=139 Participants Aclidinium bromide 200 μg dose twice per day, inhaled for 12 weeks of treatment.	Aclidinium Bromide 400 μg n=132 Participants Inhaled Aclidinium bromide 400 μg twice per day for 12 weeks.
Part B: Morning Predose (Trough) FEV1	0.045 L Standard Deviation 0.021	0.029 L Standard Deviation 0.020	0.048 L Standard Deviation 0.021

SECONDARY outcome

Timeframe: Change from baseline (Week 0) to Week 12

Population: Of 544 patients randomized, 542 patients received at least 1 dose of double-blind treatment and were included in the Safety Population. Of these patients, 541 had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the Intent to Treat (ITT) Population.

Change from baseline in peak FEV1 at week 12, Last Observation Carried Forward (LOCF)

Outcome measures

Measure	Placebo n=182 Participants Dose-matched placebo twice per day, inhaled for 12 weeks of treatment.	Aclidinium Bromide 200 μg n=182 Participants Aclidinium bromide 200 μg dose twice per day, inhaled for 12 weeks of treatment.	Aclidinium Bromide 400 μg n=177 Participants Inhaled Aclidinium bromide 400 μg twice per day for 12 weeks.
Part A: Peak Forced Expiratory Volume in 1 Second (FEV1)	0.087 L Standard Error 0.018	0.202 L Standard Error 0.018	0.212 L Standard Error 0.018

SECONDARY outcome

Timeframe: Change from baseline (Week 0) to 52 Weeks

Population: A total of 544 patients were randomized, with 542 in the Part A Safety population. Of the 454 patients who completed Part A, 448 patients continued into Part B, receiving at least 1 dose of open-label treatment, were included in the Part B Safety Population. Of these patients, 405 had a baseline and postbaseline assessment for the ITT Population.

Change from Baseline in Peak FEV1 (L) at Week 52, Last Observation Carried Forward (LOCF)

Outcome measures

Measure	Placebo n=134 Participants Dose-matched placebo twice per day, inhaled for 12 weeks of treatment.	Aclidinium Bromide 200 μg n=139 Participants Aclidinium bromide 200 μg dose twice per day, inhaled for 12 weeks of treatment.	Aclidinium Bromide 400 μg n=132 Participants Inhaled Aclidinium bromide 400 μg twice per day for 12 weeks.
Part B: Peak FEV1	0.185 L Standard Error 0.023	0.176 L Standard Error 0.023	0.172 L Standard Error 0.023

Adverse Events

Placebo - Part A

Serious events: 12 serious events

Other events: 22 other events

Deaths: 0 deaths

Aclidinium Bromide 200 μg - Part A

Serious events: 11 serious events

Other events: 20 other events

Deaths: 0 deaths

Aclidinium Bromide 400 μg - Part A

Serious events: 8 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo to Aclidinium Bromide 400 μg - Part B

Serious events: 15 serious events

Other events: 37 other events

Deaths: 0 deaths

Aclidinium Bromide 200μg to Aclidinium Bromide 400μg - Part B

Serious events: 20 serious events

Other events: 50 other events

Deaths: 0 deaths

Aclidinium Bromide 400μg to Aclidinium Bromide 400μg - Part B

Serious events: 14 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo - Part A n=182 participants at risk Dose matched placebo, twice per day, oral inhalation for 12 weeks of double-blind treatment.	Aclidinium Bromide 200 μg - Part A n=183 participants at risk Aclidinium bromide 200 microgram dose, oral inhalation, twice per day for 12 weeks of double-blind treatment.	Aclidinium Bromide 400 μg - Part A n=177 participants at risk Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 12 weeks of double-blind treatment.	Placebo to Aclidinium Bromide 400 μg - Part B n=147 participants at risk After week 12 (conclusion of Part A), patients who were on placebo received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.	Aclidinium Bromide 200μg to Aclidinium Bromide 400μg - Part B n=154 participants at risk Part B - After week 12 (conclusion of Part A), patients who were on a double-blind, 200 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at a 400 microgram dose for an additional 40 weeks.	Aclidinium Bromide 400μg to Aclidinium Bromide 400μg - Part B n=147 participants at risk After week 12 (conclusion of Part A), patients who were on a double-blind, 400 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at the same 400 microgram dose for an additional 40 weeks.
Infections and infestations Staphylococcal skin infection	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	3.3% 6/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	2.7% 5/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	2.8% 5/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	2.7% 4/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	4.5% 7/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	2.0% 3/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Cardiac disorders Coronary artery disease	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	1.4% 2/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	1.3% 2/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Cardiac disorders Acute myocardial infarction	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	1.4% 2/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Blood and lymphatic system disorders Anaemia	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Cardiac disorders Cardiac arrest	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Cardiac disorders Cardiac failure congestive	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	1.3% 2/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Nervous system disorders Cerebrovascular accident	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
General disorders Non-cardiac chest pain	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Pneumonia	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Gastrointestinal disorders Abdominal pain	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Infections and infestations Bronchitis	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Cardiac disorders Cardio-respiratory arrest	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.56% 1/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Nervous system disorders Carotid artery stenosis	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
General disorders Chest pain	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Infections and infestations Clostridium difficile colitis	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Reproductive system and breast disorders Cystocele	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Infections and infestations Diverticulitis	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Injury, poisoning and procedural complications Haematoma	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Vascular disorders Hypotension	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Infections and infestations Influenza	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Infections and infestations Lobar pneumonia	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.55% 1/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Nervous system disorders Lumbar radiculopathy	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Psychiatric disorders Mental status changes	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Nervous system disorders Migraine	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Cardiac disorders Myocardial ischaemia	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Infections and infestations Osteomyelitis	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Infections and infestations Osteomyelitis bacterial	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Gastrointestinal disorders Pancreatitis	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Renal and urinary disorders Renal failure acute	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.55% 1/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Infections and infestations Staphylococcal bacteraemia	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Infections and infestations Staphylococcal sepsis	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Reproductive system and breast disorders Uterine haemorrhage	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Nervous system disorders VIIth nerve paralysis	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.68% 1/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Reproductive system and breast disorders Vulvar dysplasia	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.65% 1/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Vascular disorders Aortic aneurysm	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.56% 1/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Gastrointestinal disorders Gastrenteritis salmonella	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.56% 1/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Pseudomonas bronchitis	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.56% 1/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Psychiatric disorders Agitated depression	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Cardiac disorders Angina pectoris	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	1.1% 2/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Cardiac disorders Atrial fibrillation	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Reproductive system and breast disorders Benign prostatic hyperplasia	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Hepatobiliary disorders Cholangitis	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Hepatobiliary disorders Cholecystitis acute	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
General disorders Death	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Metabolism and nutrition disorders Dehydration	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.55% 1/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Gastrointestinal disorders Diarrhoea	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.55% 1/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Gastrointestinal disorders Duodenal ulcer	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.55% 1/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Injury, poisoning and procedural complications Fall	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.55% 1/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.55% 1/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Injury, poisoning and procedural complications Joint injury	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.55% 1/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Ear and labyrinth disorders Labyrinthitis	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Lung adenocarcinoma	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.55% 1/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Psychiatric disorders Suicidal ideation	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Vascular disorders Transient ischaemic attack	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.55% 1/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	0.00% 0/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).

Other adverse events

Measure	Placebo - Part A n=182 participants at risk Dose matched placebo, twice per day, oral inhalation for 12 weeks of double-blind treatment.	Aclidinium Bromide 200 μg - Part A n=183 participants at risk Aclidinium bromide 200 microgram dose, oral inhalation, twice per day for 12 weeks of double-blind treatment.	Aclidinium Bromide 400 μg - Part A n=177 participants at risk Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 12 weeks of double-blind treatment.	Placebo to Aclidinium Bromide 400 μg - Part B n=147 participants at risk After week 12 (conclusion of Part A), patients who were on placebo received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.	Aclidinium Bromide 200μg to Aclidinium Bromide 400μg - Part B n=154 participants at risk Part B - After week 12 (conclusion of Part A), patients who were on a double-blind, 200 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at a 400 microgram dose for an additional 40 weeks.	Aclidinium Bromide 400μg to Aclidinium Bromide 400μg - Part B n=147 participants at risk After week 12 (conclusion of Part A), patients who were on a double-blind, 400 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at the same 400 microgram dose for an additional 40 weeks.
Respiratory, thoracic and mediastinal disorders COPD exacerbation	11.5% 21/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	8.7% 16/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	13.0% 23/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	16.3% 24/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	22.7% 35/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	27.9% 41/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Infections and infestations Upper respiratory tract infection	0.55% 1/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	1.6% 3/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	1.7% 3/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	6.1% 9/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	5.8% 9/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	5.4% 8/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	0.00% 0/182 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	1.1% 2/183 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	1.1% 2/177 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	4.1% 6/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	5.8% 9/154 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).	4.1% 6/147 • Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).

Additional Information

AstraZeneca Clinical

Study Information Center

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.
• Publication restrictions are in place

Restriction type: OTHER