Trial Outcomes & Findings for Complementary and Alternative Medicine for Urological Symptoms(CAMUS) (NCT NCT00603304)

Last Updated: 2012-10-12

Results Overview

The primary outcome was the mean difference in the AUA Symptom Score between baseline and 72 weeks between the saw palmetto and placebo groups. The AUA Symptom Score index is a seven item questionnaire assessing the frequency of lower urinary tract symptoms (LUTS). The questions are scored on a scale of zero to five, with zero being never, one to four being one to four accordingly, and five equaling five or more times. A Symptom Index is determined by adding the scores. The lowest possible score is 0 and the highest possible score is 35, which would represent the highest level of pain and discomfort.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

369 participants

Primary outcome timeframe

Baseline to 72 weeks

Results posted on

2012-10-12

Participant Flow

A total of 1032 men were prescreened for Complementary and Alternative Medicine for Urological Symptoms (CAMUS), usually by telephone; interested and preliminary eligible men were scheduled for a first screening visit.

Participant milestones

Participant milestones
Measure	Saw Palmetto Participants received one, two, and then three 320 mg chocolate-colored soft gelcaps containing a standardized saw palmetto fruit extract with dose escalations at 24 and 48 weeks.	Placebo Participants received either one, two, and then three 320 mg chocolate-colored placebo gelcaps with dose escalations at 24 and 48 weeks.
Overall Study STARTED	183	186
Overall Study COMPLETED	151	155
Overall Study NOT COMPLETED	32	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Saw Palmetto Participants received one, two, and then three 320 mg chocolate-colored soft gelcaps containing a standardized saw palmetto fruit extract with dose escalations at 24 and 48 weeks.	Placebo Participants received either one, two, and then three 320 mg chocolate-colored placebo gelcaps with dose escalations at 24 and 48 weeks.
Overall Study Lost to Follow-up	5	7
Overall Study Withdrawal by Subject	8	5
Overall Study Protocol Violation	1	0
Overall Study Adverse Event	4	2
Overall Study Unacceptable Treatment Toxicity	5	8
Overall Study Crossed Over to Open Label Therapy	3	3
Overall Study Exclusionary Medication	2	3
Overall Study Non-Compliant	0	1
Overall Study Moved Away	0	2
Overall Study Other	2	0
Overall Study Patient Decision	2	0

Baseline Characteristics

Complementary and Alternative Medicine for Urological Symptoms(CAMUS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saw Palmetto n=183 Participants Participants received one, two, and then three 320 mg chocolate-colored soft gelcaps containing a standardized saw palmetto fruit extract with dose escalations at 24 and 48 weeks.	Placebo n=186 Participants Participants received either one, two, and then three 320 mg chocolate-colored placebo gelcaps with dose escalations at 24 and 48 weeks.	Total n=369 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	123 Participants n=5 Participants	125 Participants n=7 Participants	248 Participants n=5 Participants
Age, Categorical >=65 years	60 Participants n=5 Participants	61 Participants n=7 Participants	121 Participants n=5 Participants
Age Continuous	61.25 years STANDARD_DEVIATION 8.72 • n=5 Participants	60.70 years STANDARD_DEVIATION 8.08 • n=7 Participants	60.86 years STANDARD_DEVIATION 8.38 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	183 Participants n=5 Participants	186 Participants n=7 Participants	369 Participants n=5 Participants
Region of Enrollment United States	167 participants n=5 Participants	169 participants n=7 Participants	336 participants n=5 Participants
Region of Enrollment Canada	16 participants n=5 Participants	17 participants n=7 Participants	33 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 72 weeks

Population: The primary analysis was a modified intention to treat analysis including all eligible participants who took at least one dose of study drug and had a least one follow-up AUA Symptom Score measurement.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
Mean and Standard Deviation of the Participant American Urological Association (AUA)Symptom Score Between Baseline and Week 72 for CAMUS Participants.	-2.20 units on a scale 95% Confidence Interval 5.83 • Interval -3.04 to -0.36	-2.99 units on a scale 95% Confidence Interval 5.65 • Interval -3.81 to -2.17

SECONDARY outcome

Timeframe: Baseline to 72 weeks

Participants' global assessments of improvement and satisfaction at the end of the study. Likert scales were transformed to a 0 - 100 scale. The lowest possible score is 0 and the highest possible score is 100, which would reflect better outcomes.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
Participants Global Assessments of Improvement and Satisfaction at End of Study. Global Assessment: Change from Baseline	49.9 units on a scale 95% Confidence Interval 26.9 • Interval 46.0 to 54.0	50.58 units on a scale 95% Confidence Interval 28.7 • Interval 46.0 to 55.0
Participants Global Assessments of Improvement and Satisfaction at End of Study. Global Assessment: Satisfaction with Symptoms	48.9 units on a scale 95% Confidence Interval 26.9 • Interval 44.9 to 52.9	50.6 units on a scale 95% Confidence Interval 28.8 • Interval 46.4 to 54.8

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the BPH Impact Index score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The BPH Index Score is a self administered 4 item index. Three questions are scored on a scale from 0 to 3, with zero being none, one being only a little, two being some, and three being a lot. One question is scored on a scale from 0 to 4, with zero being none of the time, one being a little of the time, two being some of the time, three being most of the time, and four being all of the time. The lowest possible score is 0 and the highest possible score is 13, which would represent the greatest dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
Benign Prostate Hyperplasia (BPH) Impact Index Score	-0.81 units on a scale 95% Confidence Interval 2.38 • Interval -1.16 to -0.46	-1.23 units on a scale 95% Confidence Interval 2.57 • Interval -1.6 to -0.87

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the IPSS Quality-of-Life Question from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The IPSS Quality-of-Life Question is an additional question to the AUA Symptom Score. The self administered question is scored on a scale from 0 to 6, with zero being delighted, one being pleased, two being mostly satisfied, three being mixed-about equally satisfied and dissatisfied, four being mostly dissatisfied, five being unhappy, and six being terrible. The lowest possible score is 0 and the highest possible score is 6, which would represent the greatest dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
International Prostate Symptom Score Quality of Life (IPSS QOL) Score	-0.34 units on a scale 95% Confidence Interval 1.26 • Interval -0.52 to -0.16	-0.49 units on a scale 95% Confidence Interval 1.27 • Interval -0.67 to -0.31

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the nocturia item of the AUA Symptom Score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The nocturia item is a self administered question from the AUA Symptom Score Index that assesses the number of times a participant typically gets up to urinate from the time he goes to bed at night until the time he gets up in the morning. The question is scored on a scale of zero to five, with zero being none, one being one time, two being two times, three being three times, four being four times, and five being five or more times. The lowest possible score is 0 and the highest possible score is 5, which would represent the highest level dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
American Urological Association(AUA) Nocturia Item	-0.36 units on a scale 95% Confidence Interval 1.22 • Interval -0.72 to 0.0	-0.15 units on a scale 95% Confidence Interval 1.22 • Interval -0.44 to 0.13

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the participants' peak uroflow from baseline to 72 weeks in the modified intention to treat analysis. The peak uroflow was measured in milliliters/seconds. The higher units indicated greater dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
Peak Uroflow	-0.18 mL/sec 95% Confidence Interval 6.03 • Interval -1.07 to 0.7	-0.79 mL/sec 95% Confidence Interval 5.55 • Interval -1.58 to 0.0

SECONDARY outcome

Timeframe: Baseline to 72 weeks

Population: The analysis population was determined by the number of participants that were randomized and included in the modified intention to treat analyses.

The mean difference in the participants' post-void residual from baseline to 72 weeks in the modified intention to treat analysis. The post-void residual was measured in milliliters. The higher units indicated greater dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
Post-void Residual	4.78 mL 95% Confidence Interval 83.70 • Interval -30.0 to 52.0	1.17 mL 95% Confidence Interval 76.12 • Interval -33.0 to 34.0

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the PSA level from baseline to 72 weeks in the modified intention to treat analysis. The PSA level was measured in nanograms/milliliters. The higher units indicated greater dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
Prostate Specific Antigen (PSA) Level	0.32 ng/mL 95% Confidence Interval 0.82 • Interval -0.08 to 0.73	-0.19 ng/mL 95% Confidence Interval 1.16 • Interval -0.53 to 0.14

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the IIEF score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The IIEF is a multidimensional scale for assessment of erectile dysfunction. The six item self administered questionnaire is scored on a scale from 0 to 5, with zero being no sexual activity, one being never or almost never, two being a few times (much less than half the time), three being sometimes (much less than half the time), four being most times (much more than half the time), and five being always or almost always. The lowest possible score is 0 and the highest possible score is 30, which represents less dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
International Index of Erectile Function (IIEF)Scale Score.	-0.52 units on a scale 95% Confidence Interval 7.59 • Interval -1.63 to 0.59	-1.06 units on a scale 95% Confidence Interval 7.39 • Interval -2.11 to -0.02

SECONDARY outcome

Timeframe: Baseline to 72 weeks.

The mean difference in the MSHQ-EjD from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The MSHQ-EjD scale is used for the assessment ejaculatory dysfunction (EjD). The MSHQ-EjD consists of four self administered questions. Three of the items are scored on a scale from 0 to 5, with zero being all the time, one being most of the time, two being some of the time, three being a little of the time, four being none of the time, and five being no sexual activity. The fourth item is scored on a scale of 1 - 5, with one being not at all bothered, two being a little bit bothered, three being moderately bothered, four being very bothered, and five being extremely bothered. The lowest possible score is 0 and the highest possible score is 20, which represents the highest level of dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
Male Sexual Health Questionnaire - Ejaculatory Domain (MSHQ-EjD) Scale Score.	-0.38 units on a scale 95% Confidence Interval 4.51 • Interval -1.04 to 0.28	-0.09 units on a scale 95% Confidence Interval 3.75 • Interval -0.63 to 0.45

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the ICSmaleIS score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The six item self administered questionnaire is scored on a scale from 0 to 4, with zero being never, one being occasionally, two being sometimes, three being most of the time, and four being all of the time. The lowest possible is 0 and the highest possible score is 24, which represents the the highest level of dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
International Continence Society Male Incontinence Symptom (ICSmale IS) Score	-0.48 units on a scale 95% Confidence Interval 2.22 • Interval -0.8 to -0.16	-0.84 units on a scale 95% Confidence Interval 2.46 • Interval -1.17 to -0.51

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the Jenkins Sleep Dysfunction score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. Jenkins Sleep Dysfunction score is used to assess sleep dysfunction. The four item self administered questionnaire is scored on a scale from 0 to 5, with zero being not at all, one being 1 -3 days, two being 4 - 7 days, three being 8 - 14 days, four being 15 - 21 days, and five being 22 - 31 days. The lowest possible score is 0 and the highest possible score is 20, which represents the highest level of dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
Jenkins Sleep Scale Score	-0.80 units on a scale 95% Confidence Interval 3.59 • Interval -1.34 to -0.27	-1.63 units on a scale 95% Confidence Interval 4.38 • Interval -2.25 to -1.01

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Pain Scale score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Pain Scale is a four item self administered questionnaire. Three of the four items are scored on a scale from 0 - 1, with zero being no and one being yes. The fourth item is scored on a scale from 0 - 10, with zero being no pain and ten being pain as bad as you can imagine. The lowest possible score is 0 and the highest possible score is 21, which represents the highest level of pain.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Pain Scale	0 units on a scale 95% Confidence Interval 2.85 • Interval -0.08 to 0.0	0 units on a scale 95% Confidence Interval 2.82 • Interval -1.0 to 0.0

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) urinary symptom scale from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) urinary symptom scale consists of two self administered questions. The questions are scored on a scale from 0 - 5, with zero being not at all, one being less than 1 time in 5, two being less than half the time, three being about half the time, four being more than half the time, and five being almost always. The lowest possible score is 0 and the highest possible score is 10, which represents the highest level of dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Urinary Symptom Scale	-0.35 units on a scale 95% Confidence Interval 2.19 • Interval -0.67 to -0.03	-0.86 units on a scale 95% Confidence Interval 2.53 • Interval -1.22 to -0.49

SECONDARY outcome

Timeframe: Baseline to 72 weeks

The mean difference in the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Quality of Life (QOL) scale from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Quality of Life (QOL) scale consists of three self administered questions. Two of the questions are scored on a scale of 0 - 3, with zero being none, one being only a little, two being some, and three being a lot. The third question is scored on a scale of 0 -6, with zero being delighted, one being pleased, two being mostly satisfied, three being mixed (equally satisfied and dissatisfied), four being mostly dissatisfied, five being unhappy, and six being terrible. The lowest possible score is 0 and the highest possible score is 12, which represents the highest level of dysfunction.

Outcome measures

Outcome measures
Measure	Saw Palmetto n=176 Participants One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 Participants One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Quality of Life (QOL)Scale	-0.85 units on a scale 95% Confidence Interval 2.14 • Interval -1.16 to -0.53	-1.08 units on a scale 95% Confidence Interval 2.16 • Interval -1.39 to -0.77

Adverse Events

Saw Palmetto

Serious events: 18 serious events

Other events: 138 other events

Deaths: 0 deaths

Placebo

Serious events: 17 serious events

Other events: 139 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Alan Cantor

University of Alabama at Birmingham

Phone: (205) 934-6887

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Saw Palmetto n=176 participants at risk One, two, and then three 320 mg gelcaps with dose escalations at 24 and 48 weeks.	Placebo n=181 participants at risk One, two, and then three 320 mg placebo gelcaps with dose escalations at 24 and 48 weeks.
Surgical and medical procedures Appendectomy for appendicitis	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Surgical and medical procedures Appendectomy for ruptured appendix	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Injury, poisoning and procedural complications Automobile accident with multiple injuries	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Surgical and medical procedures Back surgery for a lumbar spinal connective tissue cyst	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Reproductive system and breast disorders Bacterial epididymitis requiring intravenous antibiotics	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder Cancer	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Nervous system disorders Cerebellar stroke	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Surgical and medical procedures Colon resection for a polyp	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Surgical and medical procedures Elective knee replacement	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Surgical and medical procedures Elective plastic surgery	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Vascular disorders Elective repair of abdominal aortic aneurysm	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Surgical and medical procedures Elective tonsillectomy and deviated nasal septum repair	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Cardiac disorders Episode of atrial fibrillation	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Renal and urinary disorders Gross hematuria	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Surgical and medical procedures Hospitalized after pacemaker insertion	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Surgical and medical procedures Hospitalized for abdominal pain, underwent laparascopic cholecystectomy	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Infections and infestations Hospitalized for cellulitis of the elbow, required intravenous antibiotics	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
General disorders Hospitalized for chest pain	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Cardiac disorders Hospitalized for chest pain due to coronary artery disease, underwent revascularization	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
General disorders Hospitalized for chest pain that proved noncardiac after the study	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Infections and infestations Hospitalized for diverticulitis	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Renal and urinary disorders Hospitalized for hypotension due to pneumonia and chronic kidney disease	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Musculoskeletal and connective tissue disorders Hospitalized for knee pain secondary to torn vastus lateralis muscle	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Infections and infestations Hospitalized for pneumonia	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hospitalized for radioactive iodine treatment for thyroid cancer	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Cardiac disorders Inferior wall myocardial infarction	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Gastrointestinal disorders Lower gastointestinal diverticular bleeding	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mestatic recurrent follicular thyroid carcinoma	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Cancer	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Infections and infestations Sepsis secondary to a pelvic fracture	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Infections and infestations Severe Gastroenteritis	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Gastrointestinal disorders Small bowel obstruction requiring laparoscopy lysis of adhesions	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Nervous system disorders Syncope with transient high grade atrioventricular block	0.57% 1/176 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.00% 0/181 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.
Gastrointestinal disorders Upper gastrointestinal bleeding requiring transfusion	0.00% 0/176 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.	0.55% 1/181 • Number of events 1 • Collected over 72 weeks The number of participants at risk was determined by the number of participants that were randomized and included in the modified intention to treat analyses.