Trial Outcomes & Findings for Zileuton With or Without Celecoxib As Chemopreventive Agents in Smokers (NCT NCT01021215)

Last Updated: 2015-04-02

Results Overview

Pre and Post treatment differences in urinary PGE-M levels measured in each treatment arm. PGE-M levels reported as median with full range (ng/mg creatinine) for Pre treatment versus Post treatment PGE-M levels among study participants compliant to treatment with evaluable urine samples at both time points (baseline and Day 6 +/- 1 day).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

84 participants

Primary outcome timeframe

Baseline and Day 6

Results posted on

2015-04-02

Participant Flow

Recruitment Period: May 5, 2010 to September 12, 2011. All recruitment done in medical clinics at Weill Cornell Medical College (WCMC), a Participating Organization within the MD Anderson Cancer Center (MDACC) Consortium.

A total of 84 subjects were enrolled, four withdrew for different reasons before beginning study medication leaving 80 subjects started on the study medication(s).

Participant milestones

Participant milestones
Measure	Arm I: Zileuton Zileuton 1200 mg twice orally twice a day on days 1-6.	Arm II: Zileuton and Celecoxib Combined Zileuton 1200 mg twice daily plus Celecoxib 200 mg twice daily on days 1-6.
Overall Study STARTED	60	20
Overall Study Received Allocated Intervention	60	20
Overall Study COMPLETED	57	20
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I: Zileuton Zileuton 1200 mg twice orally twice a day on days 1-6.	Arm II: Zileuton and Celecoxib Combined Zileuton 1200 mg twice daily plus Celecoxib 200 mg twice daily on days 1-6.
Overall Study Lost to Follow-up	3	0

Baseline Characteristics

Zileuton With or Without Celecoxib As Chemopreventive Agents in Smokers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I: Zileuton n=60 Participants Zileuton 1200 mg twice orally twice a day on days 1-6.	Arm II: Zileuton and Celecoxib n=20 Participants Combined Zileuton 1200 mg twice daily plus Celecoxib 200 mg twice daily on days 1-6.	Total n=80 Participants Total of all reporting groups
Age, Continuous	45 years n=5 Participants	43 years n=7 Participants	43 years n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	8 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	12 Participants n=7 Participants	48 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	28 Participants n=5 Participants	7 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	10 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants	20 participants n=7 Participants	80 participants n=5 Participants
Smoking (Packs per Year)	19.5 cigarette packs n=5 Participants	19.5 cigarette packs n=7 Participants	19.5 cigarette packs n=5 Participants
Baseline PGE-M (ng/mg Cr)	12.8 ng/mg Cr n=5 Participants	10.2 ng/mg Cr n=7 Participants	12.6 ng/mg Cr n=5 Participants
Baseline LTE4 (pg/mg CR)	107 pg/mg CR n=5 Participants	86.5 pg/mg CR n=7 Participants	102.5 pg/mg CR n=5 Participants
Gender, Male/Female: Compliant Participants Female	19 participants n=5 Participants	8 participants n=7 Participants	27 participants n=5 Participants
Gender, Male/Female: Compliant Participants Male	33 participants n=5 Participants	10 participants n=7 Participants	43 participants n=5 Participants
Race, Compliant Participants American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race, Compliant Participants Asian	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Race, Compliant Participants Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race, Compliant Participants Black or African American	28 participants n=5 Participants	7 participants n=7 Participants	35 participants n=5 Participants
Race, Compliant Participants White	24 participants n=5 Participants	9 participants n=7 Participants	33 participants n=5 Participants
Race, Compliant Participants Unknown or Not Reported	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Age, Continuous, Compliant Participants	43.8 years STANDARD_DEVIATION 9.6 • n=5 Participants	43.1 years STANDARD_DEVIATION 7.6 • n=7 Participants	43.6 years STANDARD_DEVIATION 9.1 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 6

Population: Seventy-seven subjects completed the entire study with seven of those excluded from analysis as non-compliant (study medications were undetectable). Urine of two participants contained interfering substances thus were excluded from PGE-M related analysis.

Outcome measures

Outcome measures
Measure	Arm I: Zileuton n=52 Participants Zileuton 1200 mg twice orally twice a day on days 1-6.	Arm II: Zileuton and Celecoxib n=16 Participants Combined Zileuton 1200 mg twice daily plus Celecoxib 200 mg twice daily on days 1-6.
Median Urinary PGE-M Levels (Pre and Post Treatment) Pre PGE-M Levels	12.8 ng/mg creatinine Interval 1.4 to 50.4	13.4 ng/mg creatinine Interval 2.3 to 35.1
Median Urinary PGE-M Levels (Pre and Post Treatment) Post PGE-M Levels	10.5 ng/mg creatinine Interval 2.0 to 34.6	3.9 ng/mg creatinine Interval 1.2 to 10.1

PRIMARY outcome

Timeframe: Baseline and day 6

Population: Seventy-seven subjects completed the entire study, three withdrew for personal reasons. Seven of those participants were excluded from analysis as non-compliant (study medications were undetectable).

Pre and Post treatment differences in urinary LTE4 levels measured in each treatment arm compared using paired t-test should the data conform to the normality assumption or one-sample Wilcoxon rank-sum test. LTE4 levels reported as median with full range (pg/mg creatinine) for Pre treatment versus Post treatment LTE4 levels among study participants compliant to treatment with evaluable urine samples at both time points (baseline and Day 6 +/- 1 day).

Outcome measures

Outcome measures
Measure	Arm I: Zileuton n=52 Participants Zileuton 1200 mg twice orally twice a day on days 1-6.	Arm II: Zileuton and Celecoxib n=18 Participants Combined Zileuton 1200 mg twice daily plus Celecoxib 200 mg twice daily on days 1-6.
Median Urinary LTE4 Levels (Pre and Post Treatment) Pre LTE4 levels	107 pg/mg creatinine Interval 4.0 to 268.0	86 pg/mg creatinine Interval 37.0 to 250.0
Median Urinary LTE4 Levels (Pre and Post Treatment) Post LTE4 levels	42 pg/mg creatinine Interval 4.0 to 292.0	30 pg/mg creatinine Interval 10.0 to 84.0

SECONDARY outcome

Timeframe: Baseline to Day 6

Population: Analysis includes only number of participants in each treatment arm with post-treatment increase in urinary PGE-M levels as measured from baseline.

Proportion of cases with a post-treatment increase in urinary PGE-M levels by comparing those treated with Zileuton and Celecoxib combined therapy compared to those treated with Zileuton alone. Pre/postchange in levels (Increase) derived from baseline level to Day 6 +/- 1 day. Differences in baseline levels between 2 treatment arms were examined using the Wilcoxon rank-sum test.

Outcome measures

Outcome measures
Measure	Arm I: Zileuton n=52 Participants Zileuton 1200 mg twice orally twice a day on days 1-6.	Arm II: Zileuton and Celecoxib n=16 Participants Combined Zileuton 1200 mg twice daily plus Celecoxib 200 mg twice daily on days 1-6.
Proportion of Cases With a Post-treatment Increase in Urinary PGE-M Levels	.37 proportion of participants	.06 proportion of participants

Adverse Events

Arm I: Zileuton

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Arm II: Zileuton and Celecoxib

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Powel H. Brown, MD Anderson Phase I/II Prevention Consortium

University of Texas (UT) MD Anderson Cancer

Phone: (713) 745-3672

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Other adverse events
Measure	Arm I: Zileuton n=60 participants at risk Zileuton 1200 mg twice orally twice a day on days 1-6.	Arm II: Zileuton and Celecoxib n=20 participants at risk Combined Zileuton 1200 mg twice daily plus Celecoxib 200 mg twice daily on days 1-6.
Gastrointestinal disorders ABDOMINAL PAIN	3.3% 2/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Respiratory, thoracic and mediastinal disorders ALLERGIC RHINITIS	3.3% 2/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	5.0% 1/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Musculoskeletal and connective tissue disorders CHEST WALL PAIN	1.7% 1/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Gastrointestinal disorders CONSTIPATION	5.0% 3/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Psychiatric disorders DEPRESSION	3.3% 2/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Gastrointestinal disorders DIARRHEA	8.3% 5/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Nervous system disorders DIZZINESS	5.0% 3/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Gastrointestinal disorders DRY MOUTH	5.0% 3/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	5.0% 1/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Gastrointestinal disorders DYSPEPSIA	3.3% 2/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Eye disorders EYE PAIN	1.7% 1/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
General disorders FATIGUE	6.7% 4/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	5.0% 1/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Gastrointestinal disorders FLATULENCE	3.3% 2/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Gastrointestinal disorders GERD	0.00% 0/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	5.0% 1/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Nervous system disorders HEADACHE	8.3% 5/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	5.0% 1/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Skin and subcutaneous tissue disorders HYPERHIDROSIS	1.7% 1/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	5.0% 1/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Vascular disorders HYPERTENSION	1.7% 1/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Psychiatric disorders INSOMNIA	1.7% 1/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
General disorders IRRITABILITY	0.00% 0/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	5.0% 1/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	3.3% 2/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Gastrointestinal disorders NAUSEA	3.3% 2/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	10.0% 2/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Vascular disorders PAIN IN EXTREMITY	1.7% 1/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Respiratory, thoracic and mediastinal disorders POSTNASAL DRIP	1.7% 1/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	10.0% 2/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Psychiatric disorders RESTLESSNESS	0.00% 0/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	5.0% 1/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Infections and infestations SINUSITIS	1.7% 1/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Respiratory, thoracic and mediastinal disorders SORE THROAT	5.0% 3/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Infections and infestations UPPER RESPIRATORY INFECTION	0.00% 0/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	5.0% 1/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.
Eye disorders WATERING EYES	1.7% 1/60 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.	0.00% 0/20 • All adverse events that occur after the informed consent signed (including run-in) until subject off study. Study period was from May 2010 to September 2011. Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.