Trial Outcomes & Findings for Long-term Extension Study of the Safety, Tolerability, and Efficacy of Aclidinium Bromide in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (LAS-MD-36) (NCT NCT00970268)

Last Updated: 2017-01-06

Results Overview

Change From Baseline (Visit 2 of lead-in Study NCT00891462, \[LAS-MD-33\]) to Week 52 (Week 64 From Start of NCT00891462, \[LAS-MD-33\]) in Morning Predose (Trough) FEV1

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

291 participants

Primary outcome timeframe

Change from baseline (visit 2 of lead-in study LAS-MD-33) to 52 weeks

Results posted on

2017-01-06

Participant Flow

Patient recruitment occurred from August of 2009 to March of 2010 and was by invitation only to patients who had completed study NCT00891462 (LAS-MD-33). In total, there were 77 individual study sites, 71 in the United States and 6 additional sites in Canada.

From the total of 291 patients enrolled, 289 patients (99.3%) received at least 1 dose of double-blind treatment and therefore were included in the Safety Population. Of these patients, 246 (84.5%) had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the Intent To Treat (ITT) Population.

Participant milestones

Participant milestones
Measure	Aclidinium Bromide 200 μg Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment.	Aclidinium Bromide 400 μg Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment.
Overall Study STARTED	139	152
Overall Study COMPLETED	96	103
Overall Study NOT COMPLETED	43	49

Reasons for withdrawal

Reasons for withdrawal
Measure	Aclidinium Bromide 200 μg Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment.	Aclidinium Bromide 400 μg Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment.
Overall Study Withdrawal by Subject	12	19
Overall Study Adverse Event	15	12
Overall Study Lack of Efficacy	3	6
Overall Study Protocol Violation	4	7
Overall Study Other Reason	3	1
Overall Study COPD Exacerbation	4	2
Overall Study Lost to Follow-up	1	2
Overall Study Inclusion/Exclusion Criteria	1	0

Baseline Characteristics

Long-term Extension Study of the Safety, Tolerability, and Efficacy of Aclidinium Bromide in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (LAS-MD-36)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aclidinium Bromide 200 μg n=137 Participants Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment.	Aclidinium Bromide 400 μg n=152 Participants Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment.	Total n=289 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 10.1 • n=5 Participants	64.4 years STANDARD_DEVIATION 10.0 • n=7 Participants	63.9 years STANDARD_DEVIATION 9.9 • n=5 Participants
Age, Customized ≥ 40 to < 60 years	49 participants n=5 Participants	40 participants n=7 Participants	89 participants n=5 Participants
Age, Customized ≥ 60 to < 70 years	51 participants n=5 Participants	67 participants n=7 Participants	118 participants n=5 Participants
Age, Customized ≥ 70 years	37 participants n=5 Participants	45 participants n=7 Participants	82 participants n=5 Participants
Gender Female	63 Participants n=5 Participants	76 Participants n=7 Participants	139 Participants n=5 Participants
Gender Male	74 Participants n=5 Participants	76 Participants n=7 Participants	150 Participants n=5 Participants
Region of Enrollment United States	128 participants n=5 Participants	138 participants n=7 Participants	266 participants n=5 Participants
Region of Enrollment Canada	9 participants n=5 Participants	14 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: Change from baseline (visit 2 of lead-in study LAS-MD-33) to 52 weeks

Population: From the total of 291 patients enrolled, 289 patients (99.3%) received at least 1 dose of double-blind treatment and therefore were included in the Safety Population. Of these patients, 246 (84.5%) had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the ITT Population

Change From Baseline (Visit 2 of lead-in Study NCT00891462, \[LAS-MD-33\]) to Week 52 (Week 64 From Start of NCT00891462, \[LAS-MD-33\]) in Morning Predose (Trough) FEV1

Outcome measures

Outcome measures
Measure	Placebo - Aclidinium Bromide 200 μg n=38 Participants Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment for patients who received 12 weeks of placebo in the lead-in study.	Aclidinium Bromide 200 μg - Aclidinium Bromide 200 μg n=76 Participants Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment in patients who also received 200 micrograms of Aclidinium bromide for 12 weeks in the lead-in study.	Placebo - Aclidinium Bromide 400 μg n=41 Participants Aclidinium bromide, 400 microgram dose, oral inhalation, twice per day for 52 weeks of treatment for patients who received 12 weeks of placebo in the lead-in study.	Aclidinium Bromide 400 μg - Aclidinium Bromide 400 μg n=91 Participants Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment in patients who also received 400 microgram of Aclidinium bromide for 12 weeks in the lead-in study.
Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1)	-0.035 L Standard Error 0.040	0.069 L Standard Error 0.028	0.069 L Standard Error 0.037	0.056 L Standard Error 0.025

SECONDARY outcome

Timeframe: 52 weeks

Change From Baseline (Visit 2 of study NCT00891462, \[LAS-MD-33\])in Peak FEV1 in liters at Week 52 (Week 64 from the start of NCT00891462, \[LAS-MD-33\]).

Outcome measures

Outcome measures
Measure	Placebo - Aclidinium Bromide 200 μg n=38 Participants Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment for patients who received 12 weeks of placebo in the lead-in study.	Aclidinium Bromide 200 μg - Aclidinium Bromide 200 μg n=76 Participants Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment in patients who also received 200 micrograms of Aclidinium bromide for 12 weeks in the lead-in study.	Placebo - Aclidinium Bromide 400 μg n=41 Participants Aclidinium bromide, 400 microgram dose, oral inhalation, twice per day for 52 weeks of treatment for patients who received 12 weeks of placebo in the lead-in study.	Aclidinium Bromide 400 μg - Aclidinium Bromide 400 μg n=91 Participants Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment in patients who also received 400 microgram of Aclidinium bromide for 12 weeks in the lead-in study.
Change From Baseline in Peak FEV1	0.111 L Standard Error 0.040	0.213 L Standard Error 0.028	0.222 L Standard Error 0.038	0.219 L Standard Error 0.025

Adverse Events

Placebo to Aclidinium Bromide 200 μg

Serious events: 7 serious events

Other events: 36 other events

Deaths: 0 deaths

Aclidinium Bromide 200 μg to Aclidinium Bromide 200 μg

Serious events: 13 serious events

Other events: 63 other events

Deaths: 0 deaths

Placebo to Aclidinium Bromide 400μg

Serious events: 7 serious events

Other events: 28 other events

Deaths: 0 deaths

Aclidinium Bromide 400μg to Aclidinium Bromide 400μg

Serious events: 13 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

AstraZeneca Clinical

Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

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

Measure	Placebo to Aclidinium Bromide 200 μg n=44 participants at risk Patients were given 12 weeks of placebo, then switched to Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment	Aclidinium Bromide 200 μg to Aclidinium Bromide 200 μg n=93 participants at risk Patients were given 12 weeks of Aclidinium bromide, 200 microgram dose, then continued with the 200 microgram dose, oral inhalation twice per day for an additional 52 weeks of treatment.	Placebo to Aclidinium Bromide 400μg n=46 participants at risk Patients were given 12 weeks of placebo, then switched to Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment	Aclidinium Bromide 400μg to Aclidinium Bromide 400μg n=106 participants at risk Patients were given 12 weeks of Aclidinium bromide, 400 microgram dose, then continued with the 400 microgram dose twice per day, oral inhalation, for an additional 52 weeks of treatment.
Infections and infestations Nasopharyngitis	9.1% 4/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	8.6% 8/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	8.7% 4/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	9.4% 10/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Infections and infestations Urinary tract infection	9.1% 4/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	4.3% 4/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	6.5% 3/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	7.5% 8/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disorder	36.4% 16/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	24.7% 23/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	30.4% 14/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	22.6% 24/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Cardiac disorders Bundle branch block left	6.8% 3/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	3.2% 3/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	0.00% 0/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.8% 3/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Gastrointestinal disorders Gastrooesophageal reflux disease	6.8% 3/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	0.00% 0/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.2% 1/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	1.9% 2/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Gastrointestinal disorders Nausea	9.1% 4/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	1.1% 1/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.2% 1/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	1.9% 2/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
General disorders Fatigue	9.1% 4/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	3.2% 3/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	0.00% 0/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.8% 3/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
General disorders Pyrexia	6.8% 3/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	0.00% 0/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	0.00% 0/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.8% 3/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Infections and infestations Upper respiratory tract infection	11.4% 5/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	6.5% 6/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	4.3% 2/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	5.7% 6/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Infections and infestations Bronchitis	6.8% 3/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	1.1% 1/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.2% 1/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	3.8% 4/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Infections and infestations Sinusitis	11.4% 5/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	6.5% 6/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.2% 1/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.8% 3/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Infections and infestations Pneumonia	6.8% 3/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	4.3% 4/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.2% 1/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	1.9% 2/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Injury, poisoning and procedural complications Fall	0.00% 0/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	6.5% 6/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	6.5% 3/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	1.9% 2/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Injury, poisoning and procedural complications Contusion	0.00% 0/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	6.5% 6/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	10.9% 5/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	0.94% 1/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Investigations Blood glucose increased	6.8% 3/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	3.2% 3/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	6.5% 3/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	0.00% 0/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Musculoskeletal and connective tissue disorders Back pain	4.5% 2/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	7.5% 7/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	0.00% 0/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	4.7% 5/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Musculoskeletal and connective tissue disorders Arthralgia	4.5% 2/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	5.4% 5/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	6.5% 3/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	3.8% 4/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Psychiatric disorders Insomnia	4.5% 2/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.2% 2/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	4.3% 2/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	5.7% 6/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.5% 2/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.2% 2/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	0.00% 0/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	5.7% 6/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Cough	4.5% 2/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	7.5% 7/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	8.7% 4/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	3.8% 4/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 1/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	7.5% 7/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	8.7% 4/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	3.8% 4/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Skin and subcutaneous tissue disorders Rash	2.3% 1/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.2% 2/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.2% 1/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	5.7% 6/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Vascular disorders Hypertension	6.8% 3/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	4.3% 4/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.2% 1/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	2.8% 3/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Nervous system disorders Headache	6.8% 3/44 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	5.4% 5/93 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	4.3% 2/46 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).	3.8% 4/106 • Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).