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Eflornithine and Sulindac in Preventing Colorectal Cancer in Patients With Colon Polyps

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00118365
Recruitment Status : Completed
First Posted : July 11, 2005
Results First Posted : January 22, 2015
Last Update Posted : January 22, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Precancerous Condition
Interventions Other: placebo
Drug: eflornithine
Drug: sulindac
Other: laboratory biomarker analysis
Enrollment 375
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Hide Arm/Group Description

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Period Title: Overall Study
Started 191 184
Completed 132 124
Not Completed 59 60
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo) Total
Hide Arm/Group Description

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Total of all reporting groups
Overall Number of Baseline Participants 191 184 375
Hide Baseline Analysis Population Description
Randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 191 participants 184 participants 375 participants
60  (8.6) 61  (8.4) 60.5  (8.40)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 191 participants 184 participants 375 participants
Female
44
  23.0%
46
  25.0%
90
  24.0%
Male
147
  77.0%
138
  75.0%
285
  76.0%
1.Primary Outcome
Title Detection of Any Adenoma at the End of the Study
Hide Description Detection of any adenoma at the end of the study. This analysis is based on the participants who had the end-of-study colonscopy procedure done.
Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis is based on the participants who had the end-of-study colonscopy procedure done.
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 138 129
Measure Type: Number
Unit of Measure: participants
Yes 17 53
No 121 76
2.Secondary Outcome
Title Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment
Hide Description This analysis is based on the participants who had the end-of-study colonscopy procedure done and their baseline PGE2 values are available. The low PGE2 is defined as the values that are below the median PGE2 value in the analysis cohort. The high PGE2 is defined as the values that are above the median PGE2 value in the analysis cohort.
Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis is based on the participants who had the end-of-study colonscopy procedure done and their baseline PGE2 values are available. The low PGE2 is defined as the values that are below the median PGE2 value in the analysis cohort. The high PGE2 is defined as the values that are above the median PGE2 value in the analysis cohort.
Arm/Group Title Eflornithine and Sulindac + Low PGE2 at Baseline Eflornithine and Sulindac + High PGE2 at Baseline Placebo + Low PGE2 at Baseline Placebo + High PGE2 at Baseline
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

baseline PGE2 values is below the median

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

baseline PGE2 values is above the median

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

baseline PGE2 value is below median

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

baseline PGE2 value is above median

Overall Number of Participants Analyzed 53 44 42 53
Measure Type: Number
Unit of Measure: participants
Yes 12 3 19 21
No 41 41 23 32
3.Secondary Outcome
Title Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment
Hide Description The low is defined as the values that are below the median putrescine level in the analysis cohort. The high is defined as the values that are above the median putrescine level in the analysis cohort.
Time Frame Up 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
In the finalized datasaet, the total number of adnoma detected in the placebo group is 55. The descrepancy in the total number of adnoma detected in placebo group between Outcome Measure 1 and this oucome is due to the revolution of the datatset. The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title Eflornithine and Sulindac + Low Putrescine at Baseline Eflornithine and Sulindac + High Putrescine at Baseline Placebo + Low Putrescine at Baseline Placebo + High Putrescine at Baseline
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

baseline Putrescine values is below the median

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

baseline Putrescine values is above the median

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

baseline Putrescine value is below median

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

baseline Putrescine value is above median

Overall Number of Participants Analyzed 70 66 62 67
Measure Type: Number
Unit of Measure: participants
Yes 7 10 24 31
No 63 56 38 36
4.Secondary Outcome
Title Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment
Hide Description

The low is defined as the ratios that are below the median spermidine-to-spermine ratio in the analysis cohort. The high is defined as the ratios that are above the median spermidine-to-spermine ratio in the analysis cohort.

In the finalized datasaet, the total number of adnoma detected in the placebo group is 55. The descrepancy in the total number of adnoma detected in placebo group between Outcome Measure 1 and this oucome is due to the revolution of the datatset.

The analysis cohort is based on the participants whose data are available and complete.

Time Frame Up 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
In the finalized datasaet, the total number of adnoma detected in the placebo group is 55. The descrepancy in the total number of adnoma detected in placebo group between Outcome Measure 1 and this oucome is due to the revolution of the datatset. The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title Eflornithine and Sulindac + Low Spd:Spm at Baseline Eflornithine and Sulindac + High Spd:Spm at Baseline Placebo + Low Spd:Spm at Baseline Placebo + High Spd:Spm at Baseline
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

baseline spermidine-to-spermine ratio is below the median

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

baseline spermidine-to-spermine ratio is above the median

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

baseline spermidine-to-spermine ratio is below median

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

baseline spermidine-to-spermine ratio is above median

Overall Number of Participants Analyzed 64 72 68 61
Measure Type: Number
Unit of Measure: participants
Yes 5 12 31 24
No 59 60 37 37
5.Secondary Outcome
Title Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment
Hide Description PGE2 Responder = PGE2 values at 36-month are decreased by >=30% in PGE2 values from baseline PGE2 nonresponder = PGE2 values at 36-month are increased, or decreased by < 30% from baseline The analysis cohort is based on the participants whose data are available and complete.
Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title Eflornithine and Sulindac + PGE2 Responders Eflornithine and Sulindac + PGE2 Nonresponders Placebo + PGE2 Responders Placebo + PGE2 Nonresponders
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

PGE2 Responder = PGE2 values at 36-month are decreased by >=30% in PGE2 values from baseline

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

PGE2 nonresponder = PGE2 values at 36-month are increased, or decreased by < 30% from baseline

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

PGE2 Responder = PGE2 values at 36-month are decreased by >=30% in PGE2 values from baseline

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

PGE2 nonresponder = PGE2 values at 36-month are increased, or decreased by < 30% from baseline

Overall Number of Participants Analyzed 11 35 17 32
Measure Type: Number
Unit of Measure: participants
Yes 1 8 4 15
No 10 27 13 17
6.Secondary Outcome
Title Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment
Hide Description Putrescine responder = Putrescine values at 36-month are decreased by >=30% from baseline Putrescine nonresponder = Putrescine values at 36-month are increased, or decreased by < 30% from baseline The analysis cohort is based on the participants whose data are available and complete.
Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title Eflornithine and Sulindac + Putrescine Responders Eflornithine and Sulindac + Putrescine Nonresponders Placebo + Putrescine Responders Placebo + Putrescine Nonresponders
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Putrescine responder = Putrescine values at 36-month are decreased by >=30% from baseline

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Putrescine nonresponder = Putrescine values at 36-month are increased, or decreased by < 30% from baseline

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Putrescine responder = Putrescine values at 36-month are decreased by >=30% from baseline

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Putrescine nonresponder = Putrescine values at 36-month are increased, or decreased by < 30% from baseline

Overall Number of Participants Analyzed 61 60 46 72
Measure Type: Number
Unit of Measure: participants
Yes 9 7 22 28
No 52 53 24 44
7.Secondary Outcome
Title Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment
Hide Description Spermidine-to-spermine ratio responder = ratios at 36-month are decreased by >=30% from baseline Spermidine-to-spermine ratio nonresponder = ratios at 36-month are increased, or decreased by < 30% from baseline The analysis cohort is based on the participants whose data are available and complete.
Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title Eflornithine and Sulindac + Spd:Spm Responders Eflornithine and Sulindac + Spd:Spm Nonresponders Placebo + Spd:Spm Responders Placebo + Spd:Spm Nonresponders
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Spd:Spm Responder = spermidine-to-spermine ratio at 36-month are decreased by >=30% from baseline

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. The treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Spd:Spm nonresponder = spermidine-to-spermine ratio at 36-month increased, or decreased by < 30% from baseline

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

SpSpd:Spm Responder = spermidine-to-spermine ratio at 36-month are decreased by >=30% from baseline

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Spd:Spm nonresponder = spermidine-to-spermine ratio at 36-month increased, or decreased by < 30% from baseline

Overall Number of Participants Analyzed 83 38 41 77
Measure Type: Number
Unit of Measure: participants
Yes 8 8 17 33
No 75 30 24 44
8.Secondary Outcome
Title Adverse Events With a Grade of 3 and Above
Hide Description

Participants reported at least 1 adverse event with a grade of 3 and above, regardless if the event is defined as serious per protocol or other.

Per protocol, not all grade 3 events are considered as serious events.

Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 191 184
Measure Type: Number
Unit of Measure: participants
46 37
9.Secondary Outcome
Title Baseline Putrescine by ODC Genotype
Hide Description ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title ODC1 AA/GA ODC1 GG
Hide Arm/Group Description:
Patients with AA or GA genotype
Patients with GG genotype
Overall Number of Participants Analyzed 101 125
Median (Full Range)
Unit of Measure: nmol/mg protein
0.47
(0.01 to 4.60)
0.56
(0.01 to 5.29)
10.Secondary Outcome
Title Baseline Spermidine by ODC Genotype
Hide Description ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title ODC1 AA/GA ODC1 GG
Hide Arm/Group Description:
Patients with AA or GA genotype
Patients with GG genotype
Overall Number of Participants Analyzed 101 125
Median (Full Range)
Unit of Measure: nmol/mg protein
1.99
(0.76 to 9.18)
2.17
(1.05 to 8.97)
11.Secondary Outcome
Title Baseline Spermine by ODC Genotype
Hide Description ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title ODC1 AA/GA ODC1 GG
Hide Arm/Group Description:
Patients with AA or GA genotype
Patients with GG genotype
Overall Number of Participants Analyzed 101 125
Median (Full Range)
Unit of Measure: nmol/mg protein
6.82
(2.29 to 19.86)
7.29
(2.72 to 22.85)
12.Secondary Outcome
Title At the End of the Study - Putrescine Response by ODC Genotype
Hide Description

Putrescine responder was defined as (tissue putrescine value at baseline - tissue putrescine value at the end of the study)/(tissue putrescine value at baseline) ≥ the threshold. Putrescine non-responder was defined as (tissue putrescine value at baseline - tissue putrescine value at the end of the study)/(tissue putrescine value at baseline) < the threshold. The thresholds range from 0.25 to 0.45 with an increment of 0.5. The below data are shown for the threshold of 0.30.

ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.

Time Frame At the end of the study
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title DFMO + Sulindac - GG DFMO + Sulindac - AA/GA Placebo - GG Placebo - AA/GA
Hide Arm/Group Description:

Patients with GG genotype receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients with AA or GA genotype receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients with GG genotype receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Patients with AA or GA genotype receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 58 40 43 49
Measure Type: Number
Unit of Measure: participants
Responder 26 21 12 12
Non-Responder 32 19 31 37
13.Secondary Outcome
Title At the End of the Study - Spermidine Response by ODC Genotype
Hide Description

Spermidine responder was defined as (tissue spermidine value at baseline - tissue spermidine value at the end of the study)/(tissue spermidine value at baseline) ≥ the threshold. Spermidine non-responder was defined as (tissue spermidine value at baseline - tissue spermidine value at the end of the study)/(tissue spermidine value at baseline) < the threshold. The thresholds range from 0.25 to 0.45 with an increment of 0.5. The below data are shown for the threshold of 0.30.

ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.

Time Frame At the end of the study
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title DFMO + Sulindac - GG DFMO + Sulindac - AA/GA Placebo - GG Placebo - AA/GA
Hide Arm/Group Description:

Patients with GG genotype receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients with AA or GA genotype receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients with GG genotype receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Patients with AA or GA genotype receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 58 40 43 49
Measure Type: Number
Unit of Measure: participants
Responder 25 12 15 11
Non-Responder 32 28 28 38
14.Secondary Outcome
Title At the End of the Study - Spermine Response by ODC Genotype
Hide Description

Spermine responder was defined as (tissue spermine value at baseline - tissue spermine value at the end of the study)/(tissue spermine value at baseline) ≥ the threshold. Spermine non-responder was defined as (tissue spermine value at baseline - tissue spermine value at the end of the study)/(tissue spermine value at baseline) < the threshold. The thresholds range from 0.25 to 0.45 with an increment of 0.5. The below data are shown for the threshold of 0.30.

ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.

Time Frame At the end of the study
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title DFMO + Sulindac - GG DFMO + Sulindac - AA/GA Placebo - GG Placebo - AA/GA
Hide Arm/Group Description:

Patients with GG genotype receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients with AA or GA genotype receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients with GG genotype receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Patients with AA or GA genotype receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 58 40 43 49
Measure Type: Number
Unit of Measure: participants
Responder 7 7 18 10
Non-Responder 51 33 25 39
15.Secondary Outcome
Title Number of Participants Have Adenoma Recurrence in Each ODC1 Genotytpe by Treatment Group
Hide Description ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available and complete.
Arm/Group Title DFMO + Sulindac - GG DFMO + Sulindac - AA/GA Placebo - GG Placebo - AA/GA
Hide Arm/Group Description:

Patients with GG genotype receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients with AA or GA genotype receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients with GG genotype receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Patients with AA or GA genotype receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 64 42 44 53
Measure Type: Number
Unit of Measure: participants
7 9 22 18
16.Secondary Outcome
Title Biomarker in Adenoma: Apoptosis
Hide Description Apoptosis expression was assessed using cytoplasmic staining. The definitions for the category level for the Apoptosis are: 1. focal (less than 10% cells that are positively stained); 2. less than 50% cells are positively stained; 3. more than 50% cells are positively stained.
Time Frame At the end of the study
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available.
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 11 38
Overall Number of Units Analyzed
Type of Units Analyzed: Adenoma
12 60
Measure Type: Number
Unit of Measure: adenoma
A pattern equal to normal mucosa 2 4
1.focal (<10%) 7 20
2.cyto less than 50% 1 23
3.cyto more than 50% 2 13
17.Secondary Outcome
Title Biomarker in Adenoma - Ki-67
Hide Description Estimated mean percent of cells staining postivie for the Ki-67 based on the GEE approach with adjustment for covariates
Time Frame At the end of the study
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available.
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 11 40
Mean (95% Confidence Interval)
Unit of Measure: percentage of cells that are positive
59.5
(48.10 to 71.02)
63.9
(57.35 to 70.39)
18.Secondary Outcome
Title Biomarker in Adenoma: CEA
Hide Description carcino-embryonic antigen (CEA) is adenocarcinoma tissue marker that is expressed during adenoma formation.
Time Frame At the end of the study
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available.
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 11 40
Overall Number of Units Analyzed
Type of Units Analyzed: Adenoma
12 66
Measure Type: Number
Unit of Measure: Adenoma
A pattern equal to normal mucosa 1 5
1.<50% of cells showed staining 5 15
2.50-90% of cells showed staining 6 35
3.>90% of cells showed staining 0 9
Insufficient tissue 0 2
19.Secondary Outcome
Title Biomarker in Adenoma: Sialyl-TN (B72.3)
Hide Description sialyl-Tn (B72.3) is adenocarcinoma tissue marker that is expressed during adenoma formation.
Time Frame At the end of the study
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available.
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 11 40
Overall Number of Units Analyzed
Type of Units Analyzed: Adenoma
12 66
Measure Type: Number
Unit of Measure: Adenoma
a pattern equal to normal mucosa 3 11
1.<10% of the cells in the adenoma showed staining 7 32
2.10-50% cells showed staining 2 17
3.>50% cells showed staining 0 5
Insufficient tissue 0 1
20.Secondary Outcome
Title Biomarker in Adenoma - p53
Hide Description

Estimated mean percent of cells staining postivie for p53 based on GEE approach with adjument for covariates.

Tumor protein p53, also known as p53, cellular tumor antigen p53, phosphoprotein p53, or tumor suppressor p53, is a protein that in humans is encoded by the TP53 gene.

Time Frame At the end of the study
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available.
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 11 40
Mean (95% Confidence Interval)
Unit of Measure: percentage of cells that are positive
75.6
(51.10 to 100.09)
70.3
(61.86 to 78.69)
21.Secondary Outcome
Title Biomarker in Adenoma: Bcl-2
Hide Description bcl-2 is the anti-apoptotic protein BCL2
Time Frame At the end of the study, up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis cohort is based on the participants whose data are available.
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Hide Arm/Group Description:

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 11 40
Overall Number of Units Analyzed
Type of Units Analyzed: Adenoma
12 66
Measure Type: Number
Unit of Measure: Adenoma
A pattern equal to normal mucosa 4 17
1.<10% of the cells in the adenoma showed staining 4 25
2.10-50% cells showed staining 3 14
3.>50% cells showed staining 1 8
Insufficient tissue 0 2
Time Frame The adverse event onset date occurred between the date of run-in and the date of off-study or date of follow-up (up to 3.5 years), when available.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Hide Arm/Group Description

Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

eflornithine: Given orally

sulindac: Given orally

laboratory biomarker analysis: Correlative studies

Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

placebo: Given orally

laboratory biomarker analysis: Correlative studies

All-Cause Mortality
Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   41/191 (21.47%)      28/184 (15.22%)    
Cardiac disorders     
ACUTE MYOCARDIAL INFARCTION *  2/191 (1.05%)  2 0/184 (0.00%)  0
ANEURYSM *  1/191 (0.52%)  1 0/184 (0.00%)  0
ANGINA *  0/191 (0.00%)  0 1/184 (0.54%)  1
AORTIC STENOSIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
CHEST PAIN *  2/191 (1.05%)  2 1/184 (0.54%)  1
CHEST PAIN AND PALPITATIONS *  1/191 (0.52%)  1 0/184 (0.00%)  0
CHEST PAIN X 3 WKS, R/O CORONARY ARTERY DISEASE *  1/191 (0.52%)  1 0/184 (0.00%)  0
CONGESTIVE HEART FAILURE *  2/191 (1.05%)  2 0/184 (0.00%)  0
CORONARY ARTERY DISEASE *  3/191 (1.57%)  3 0/184 (0.00%)  0
CORONARY ARTERY DISEASE POST NON-ST ELEVATION MI *  0/191 (0.00%)  0 1/184 (0.54%)  1
CORONARY ARTERY DISORDER *  0/191 (0.00%)  0 1/184 (0.54%)  2
DISCHARGE SUMMARY 1/27/02 NEW ONSET ATRIAL FIBRILLATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEART DISEASE: A. CORONARY, B. NON-Q-WAVE INFARCTION, C. UNSTABLE ANGINA; CORONARY STENTING *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFARCT MYOCARDIAL *  1/191 (0.52%)  1 0/184 (0.00%)  0
MYOCARDIAL INFARCTION/CHEST PAIN, ABNORMAL CARDIAC ENZYMES *  1/191 (0.52%)  1 0/184 (0.00%)  0
PAIN CHEST *  0/191 (0.00%)  0 1/184 (0.54%)  1
QUADRUPLE BYPASS SURGERY FOR CAD, UNSTABLE ANGINA *  1/191 (0.52%)  1 0/184 (0.00%)  0
R/O MI *  0/191 (0.00%)  0 1/184 (0.54%)  1
STERNAL WOUND SURGICAL DEBRIDEMENT *  1/191 (0.52%)  1 0/184 (0.00%)  0
Endocrine disorders     
PARATHYROID DISORDER *  1/191 (0.52%)  1 0/184 (0.00%)  0
Gastrointestinal disorders     
ABDOMINAL PAIN MOST LIKELY SECONDARY TO ACUTE CHOLECYSTITIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
COLITIS PSEUDOMEMBRANOUS *  0/191 (0.00%)  0 1/184 (0.54%)  1
DIVERTICULITIS *  0/191 (0.00%)  0 1/184 (0.54%)  1
GASTROINTESTINAL BLEEDING *  1/191 (0.52%)  1 0/184 (0.00%)  0
GASTROINTESTINAL BLEEDING SECONDARY TO ACUTE GASTROENTERITIS *  0/191 (0.00%)  0 1/184 (0.54%)  1
GI BLEED R/T DIVERTICULA *  1/191 (0.52%)  1 0/184 (0.00%)  0
HOSPITALIZATION; APPENDICITIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
INTESTINAL ILEUS STATUS POST CHOLECYSTECTOMY *  0/191 (0.00%)  0 1/184 (0.54%)  1
OBSTRUCCTIVE JAUNDICE *  1/191 (0.52%)  1 0/184 (0.00%)  0
PT. ADMITTED TO HOSPITAL FOR SPIGELIAN HERNIA REPAIR *  0/191 (0.00%)  0 1/184 (0.54%)  1
RENAL CYST *  0/191 (0.00%)  0 1/184 (0.54%)  1
Hepatobiliary disorders     
CHOLECYSTITIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
GALLSTONES, PANCREATITIS *  0/191 (0.00%)  0 1/184 (0.54%)  1
Infections and infestations     
PANCREATITIS *  1/191 (0.52%)  2 1/184 (0.54%)  1
SEPSIS *  0/191 (0.00%)  0 1/184 (0.54%)  1
URINARY TRACT INFECTION, HYPERGLYCEMIA *  0/191 (0.00%)  0 1/184 (0.54%)  1
UTI WITH SEPSIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
Musculoskeletal and connective tissue disorders     
BROKEN RIGHT TIBIA UNDER KNEE D/T MVA *  1/191 (0.52%)  1 0/184 (0.00%)  0
FX (L) ELBOW *  1/191 (0.52%)  1 0/184 (0.00%)  0
HOSPITALIZATION; FRACTURE OF LEFT ANKLE REQUIRING SURGICAL INTERVENTION *  1/191 (0.52%)  1 0/184 (0.00%)  0
JOINT DISORDER *  0/191 (0.00%)  0 1/184 (0.54%)  1
LUMBAR HERNIATED DISC AND LUMBAR RADICULOPATHY *  1/191 (0.52%)  1 0/184 (0.00%)  0
MVA *  1/191 (0.52%)  1 0/184 (0.00%)  0
PT WAS IN A MOTOR VEHICLE ACCIDENT…RECEIVED CONTUSIONS AND EXPERIENCED HEAD PAIN. PT WAS RESTRAINED. *  0/191 (0.00%)  0 1/184 (0.54%)  1
RIGHT HIP PAIN *  1/191 (0.52%)  1 0/184 (0.00%)  0
RIGHT KNEE PAIN *  1/191 (0.52%)  1 0/184 (0.00%)  0
S/P LEFT TOTAL HIP ARTHROSCOPY *  0/191 (0.00%)  0 1/184 (0.54%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
CARCINOMA PROSTATIC *  1/191 (0.52%)  1 0/184 (0.00%)  0
HOSPITALIZATION FOR PANCREATIC NEOPLASM *  1/191 (0.52%)  1 0/184 (0.00%)  0
PANCREATIC CANCER *  0/191 (0.00%)  0 1/184 (0.54%)  1
Nervous system disorders     
BENIGN POSITIONAL VERTIGO *  0/191 (0.00%)  0 1/184 (0.54%)  1
CEREBRAL INFARCTION *  1/191 (0.52%)  1 0/184 (0.00%)  0
CEREBROVASCULAR ACCIDENT *  0/191 (0.00%)  0 1/184 (0.54%)  1
PROBABLE RIGHT SUBCORTICAL INFARCT *  1/191 (0.52%)  1 0/184 (0.00%)  0
SEIZURE ACTIVITY SECONDARY TO CEREBRAL ATROPHY OF RIGHT TEMPORAL LOBE *  0/191 (0.00%)  0 1/184 (0.54%)  1
Psychiatric disorders     
BIPOLAR, EXACERBATED *  1/191 (0.52%)  1 0/184 (0.00%)  0
DEPRESSION SUICIDAL *  0/191 (0.00%)  0 1/184 (0.54%)  1
MENTAL AND PHYSICAL BREAKDOWN *  1/191 (0.52%)  1 0/184 (0.00%)  0
Renal and urinary disorders     
BLADDER PROLAPSE *  0/191 (0.00%)  0 1/184 (0.54%)  1
HOSPITALIZATION - OVERNIGHT OBSERVATION; LEFT KIDNEY BIOPSY *  1/191 (0.52%)  1 0/184 (0.00%)  0
HOSPITALIZATION UTI *  1/191 (0.52%)  1 0/184 (0.00%)  0
HOSPITALIZED FOR ELECTIVE BLADDER SURGERY TO EVALUATE INCONTINENCE AND BIOPSY POSSIBLE TUMOR. *  0/191 (0.00%)  0 1/184 (0.54%)  1
KIDNEY CALCULUS *  1/191 (0.52%)  1 0/184 (0.00%)  0
NEPHROPATHY TOXIC *  0/191 (0.00%)  0 1/184 (0.54%)  1
RENAL FAILURE ACUTE *  0/191 (0.00%)  0 1/184 (0.54%)  1
Reproductive system and breast disorders     
DUCTAL LEFT BREAST CANCER *  0/191 (0.00%)  0 1/184 (0.54%)  1
HOSPITALIZATION VAGINAL BLEEDING TOTAL HYSTERECTOMY *  1/191 (0.52%)  1 0/184 (0.00%)  0
HOSPITALIZATION; BENIGN PROSTATIC HYPERTROPHY; ADMITTED FOR TRANSURETHRAL RESECTION OF THE PROSTATE *  0/191 (0.00%)  0 1/184 (0.54%)  1
LEFT URETERAL STONES, OBSTRUCTING *  1/191 (0.52%)  1 0/184 (0.00%)  0
PROLAPSED CYSTOCELE; TOTAL HYSTERECTOMY WITH BILATERAL SALPINGO-OOPHORECTOMY *  1/191 (0.52%)  1 0/184 (0.00%)  0
PROSTATE CANCER *  0/191 (0.00%)  0 1/184 (0.54%)  1
Respiratory, thoracic and mediastinal disorders     
ACUTE SHORTNESS OF BREATH R/T CHF, IMPROVED *  1/191 (0.52%)  1 0/184 (0.00%)  0
ACUTE SHORTNESS OF BREATH; CAD; UNSTABLE ANGINA *  1/191 (0.52%)  1 0/184 (0.00%)  0
ARRYTHMIA SINUS *  1/191 (0.52%)  1 0/184 (0.00%)  0
COPD EXACERBATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
DYSPNEA *  0/191 (0.00%)  0 1/184 (0.54%)  1
MALIGNANT EPITHELOID NEOPLASM *  0/191 (0.00%)  0 1/184 (0.54%)  1
PNEUMONIA *  1/191 (0.52%)  1 0/184 (0.00%)  0
PNEUMONIA, SEPSIS SYNDROME, ACUTE RENAL FAILURE *  0/191 (0.00%)  0 1/184 (0.54%)  1
PNEUMONIA; POSSIBLE COPD EXACERBATION *  1/191 (0.52%)  1 0/184 (0.00%)  0
Skin and subcutaneous tissue disorders     
BASAL CELL CARCINOMA *  1/191 (0.52%)  1 0/184 (0.00%)  0
CELLULITIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
CELLULITIS OF RIGHT LEG *  1/191 (0.52%)  1 0/184 (0.00%)  0
LEFT LEG CELLULITIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm I (Eflornithine and Sulindac) Arm II (Placebo)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   173/191 (90.58%)      154/184 (83.70%)    
Cardiac disorders     
A-FIB *  0/191 (0.00%)  0 1/184 (0.54%)  1
BLOOD IN STOOL SMALL DOT *  1/191 (0.52%)  1 0/184 (0.00%)  0
CAD *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* ALTERED LEFT VENTRICULAR DIASTOLIC FUNCTION *  0/191 (0.00%)  0 1/184 (0.54%)  1
CARDIAC* ATRIAL FIBRILLATION *  0/191 (0.00%)  0 2/184 (1.09%)  2
CARDIAC* CONGESTIVE HEART FAILURE *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* DX -- POSSIBLE RETURN OF RENOVASCULAR HTN *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* DX WITH CAD *  0/191 (0.00%)  0 1/184 (0.54%)  1
CARDIAC* FLUID IN LUNGS *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* HEART ATTACK *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* HEART MURMUR *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* HEART PALPITATIONS AND HYPERTENSION *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* LEFT BUNDLE BRANCH BLOCK *  0/191 (0.00%)  0 1/184 (0.54%)  1
CARDIAC* MILD AORTIC SCLEROSIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* MYOCARDIAL INFARCTION BY EKG *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* NEAR FAINT EPISODES, DX HTN, ON DRUGS *  0/191 (0.00%)  0 1/184 (0.54%)  1
CARDIAC* PALPITATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
CARDIAC* PALPITATIONS (PSVT) *  0/191 (0.00%)  0 1/184 (0.54%)  1
CARDIAC* TACHYCARDIA *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* TACHYCARDIA EPISODES - INCREASED FREQUENCY *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* UNSTABLE ANGINA, CHEST PAIN *  1/191 (0.52%)  1 0/184 (0.00%)  0
CARDIAC* VALVULAR HEART DISEASE - MILVAL VALVE REGURGITATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
CARDIAC* VASOVAGAL EPISODE *  1/191 (0.52%)  2 0/184 (0.00%)  0
CARDIAC* VASOVAGAL SYNCOPAL EPISODE *  0/191 (0.00%)  0 1/184 (0.54%)  1
CHEST PAIN RELATED TO 4/18 REPORT FOR HEART BURN *  1/191 (0.52%)  1 0/184 (0.00%)  0
CHEST PAIN WITH EXERTION *  1/191 (0.52%)  1 0/184 (0.00%)  0
DX CHF *  0/191 (0.00%)  0 1/184 (0.54%)  1
ELEVATED BLOOD PRESSURE *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEART DISEASE *  0/191 (0.00%)  0 1/184 (0.54%)  1
HIGH BLOOD PRESSURE *  1/191 (0.52%)  1 0/184 (0.00%)  0
HTN *  1/191 (0.52%)  1 0/184 (0.00%)  0
HYPERTENSION *  6/191 (3.14%)  7 6/184 (3.26%)  7
HYPERTENSION /DIABETES *  1/191 (0.52%)  1 0/184 (0.00%)  0
HYPERTENSION MILD/MOD *  1/191 (0.52%)  1 0/184 (0.00%)  0
HYPERTENSION RETURNED *  1/191 (0.52%)  1 0/184 (0.00%)  0
HYPERTENSION SUSPECT OCULAR HYPERTENSION *  1/191 (0.52%)  1 0/184 (0.00%)  0
HYPERTENSION UNCONTROLLED *  0/191 (0.00%)  0 1/184 (0.54%)  1
INCREASE BP WITH RINGING IN EARS *  0/191 (0.00%)  0 1/184 (0.54%)  1
OCC. CHEST TIGHTNESS *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* CLAUDICATION *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* ELEVATED BLOOD PRESSURE/ SINGLE EVENT 9/00 *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* ELEVATED BLOOD PRESSURE; SINGLE 9/00 *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* HTN *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* HTN (R/T STRESS AND WEIGHT) *  0/191 (0.00%)  0 1/184 (0.54%)  1
PAIN* CHEST *  2/191 (1.05%)  2 0/184 (0.00%)  0
PAIN* CHEST DISCOMFORT *  0/191 (0.00%)  0 1/184 (0.54%)  1
PAIN* CHEST; EXACERBATION OF PREVIOUS CONDITION *  1/191 (0.52%)  1 0/184 (0.00%)  0
Ear and labyrinth disorders     
BLEEDING* EAR CANALS, LEFT AND RIGHT *  0/191 (0.00%)  0 1/184 (0.54%)  1
CHANGE *  1/191 (0.52%)  1 0/184 (0.00%)  0
CHANGE IN HEARING PER AUDIOGRAM *  1/191 (0.52%)  1 0/184 (0.00%)  0
CHANGE IN SIGNIFICANT OTHER'S PERCEPTION OF HEARING *  1/191 (0.52%)  1 0/184 (0.00%)  0
CN VIII *  0/191 (0.00%)  0 1/184 (0.54%)  1
EAR INFECTION *  1/191 (0.52%)  1 2/184 (1.09%)  2
HEARING *  5/191 (2.62%)  5 5/184 (2.72%)  7
HEARING "CARBONIZATION SOUND" - LEFT EAR *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING /INNER EAR - "STATIC NOISE" LEFT *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING AUDIO CHANGE *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING AUDIO CHANGE SUBCLINICAL *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING AUDIO SHOWS NO CHANGE *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING AUDIOGRAM *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING AUDIOGRAM CHANGE *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING AUDIOGRAM GRADE 1 HEARING CHANGE *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING AUDIOGRAM ONLY *  2/191 (1.05%)  2 0/184 (0.00%)  0
HEARING AUDIOMETIC CHANGE, OFF STUDY *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING AUDIOMETRIC CHANGE *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING AUDIOMETRIC CHANGE BILATERAL *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING AUDIOMETRIC CHANGE LEFT EAR *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING AUDIOMETRIC CHANGE RIGHT EAR *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING AUDIOMETRIC CHANGE RIGHT EAR/ OVERALL NO SIGNIFICANT CHANGE *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING AUDITORY *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING CHANGE *  11/191 (5.76%)  13 6/184 (3.26%)  6
HEARING CHANGE AUDIOGRAM *  2/191 (1.05%)  2 1/184 (0.54%)  1
HEARING CHANGE NOTED ON AUDIO *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING CHANGE PER AUDIOGRAM *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING CHANGE-LEFT EAR *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING CHANGE? PT NOT SURE *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING DECREASE IN HEARING *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING DECREASE IN HEARING ABILITY *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING DECREASE LEFT>RIGHT *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING DECREASED *  1/191 (0.52%)  1 1/184 (0.54%)  1
HEARING DECREASED RIGHT EAR *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING DIFFICULTY *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING HEARING CHANGE *  3/191 (1.57%)  3 3/184 (1.63%)  3
HEARING HEARING LOSS *  2/191 (1.05%)  2 3/184 (1.63%)  3
HEARING HEARING LOSS - SIGNIFICANT OTHER PERCEPTION *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING HEARING LOSS AUDIOMETRY ONLY *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING HEARNING LOSS/ SUBCLINICAL *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING HEARS PULSE IN LEFT EAR *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING HUSBAND THINKS POSSIBLE HEARING CHANGE *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING INNER EAR *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING LOSS *  3/191 (1.57%)  3 2/184 (1.09%)  3
HEARING LOSS (SELF-PERCEPTION) *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING LOSS + PAIN, LEFT NECK *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING LOSS - SIGNIFICANT OTHER PERCEPTION *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING LOSS IN LEFT EAR *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING LOSS IN LEFT EAR, AUDIO DONE 11-30-00 *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING MILD LOSS *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING MUFFLED *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING OTITIS MEDIA *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING OTOTOXICITY *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING OTOTOXICITY - AUDIOGRAM ONLY *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING PLUGGED RIGHT EAR *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING POSSIBLE CHANGE *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING RIGHT EAR "PLUGGED" X2 EPISODES *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING RIGHT EAR PAIN/PLUG *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING RIGHT EAR PAIN/PLUG, EUSTACHIAN TUBE DYSFUNCTION *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEARING SELF PERCEPTION *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING SELF PERCEPTION, DIFFICULTY WITH DISCRIMINATION *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING SLIGHT LOSS *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARING TINNITUS (HAS GOTTEN SLIGHTLY WORSE OVER LAST 2 MONTHS) *  0/191 (0.00%)  0 1/184 (0.54%)  1
LEFT EAR INFECTION, RINGING WITH FULLNESS *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* DISCOMFORT LEFT EAR *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* EAR DISCHARGE *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* EAR PAIN AND PRESSURE *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* RIGHT EAR PRESSURE *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTOTOXICITY* LEFT EAR *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTOTOXICITY* R/EAR CLOGGED *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTOTOXICITY* TINNITUS LEFT EAR *  1/191 (0.52%)  1 0/184 (0.00%)  0
PAIN* EAR *  0/191 (0.00%)  0 1/184 (0.54%)  1
PAIN* EAR ACHE *  1/191 (0.52%)  1 1/184 (0.54%)  1
PAIN* EAR PAIN *  1/191 (0.52%)  1 0/184 (0.00%)  0
RIGHT EAR SENSORAL HEARING LOSS -- AGE RELATED PER ENT MD *  0/191 (0.00%)  0 1/184 (0.54%)  1
RIGHT SIDE ABOVE EAR *  1/191 (0.52%)  1 0/184 (0.00%)  0
SIGNIFICANT OTHER PERCEPTION OF CHANGE IN HEARING *  0/191 (0.00%)  0 1/184 (0.54%)  1
TINNITUS *  12/191 (6.28%)  12 8/184 (4.35%)  11
TINNITUS - SLIGHT INTERFERRENCE *  0/191 (0.00%)  0 1/184 (0.54%)  1
TINNITUS CHRONIC *  0/191 (0.00%)  0 1/184 (0.54%)  1
TINNITUS INCREASE *  0/191 (0.00%)  0 1/184 (0.54%)  1
TINNITUS INCREASE, LEFT EAR *  0/191 (0.00%)  0 1/184 (0.54%)  1
TINNITUS INCREASED *  0/191 (0.00%)  0 1/184 (0.54%)  1
TINNITUS INCREASED, LEFT EAR *  1/191 (0.52%)  1 0/184 (0.00%)  0
TINNITUS LEFT EAR *  0/191 (0.00%)  0 1/184 (0.54%)  1
TINNITUS MAY HAVE INCREASED *  1/191 (0.52%)  1 0/184 (0.00%)  0
TINNITUS MILD INCREASE, AUDIO AT 6M *  0/191 (0.00%)  0 1/184 (0.54%)  1
TINNITUS PRE-EXISTING - INCREASED *  1/191 (0.52%)  1 0/184 (0.00%)  0
TINNITUS VERY SLIGHT *  1/191 (0.52%)  1 0/184 (0.00%)  0
TINNITUS X1 EPISODE *  1/191 (0.52%)  1 0/184 (0.00%)  0
TINNITUS X4 EPISODES *  0/191 (0.00%)  0 1/184 (0.54%)  1
Endocrine disorders     
DIABETES NEW ONSET *  0/191 (0.00%)  0 1/184 (0.54%)  1
ENLARGED THYROID *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* DECREASED THYROID FUNCTION, THIN HAIR, DECREASED TEMP, DRY SKIN *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* DIABETES *  2/191 (1.05%)  2 0/184 (0.00%)  0
OTHER* DIABETIC NEUROPATHY *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* DX OF DIABETES *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* ENDOCRINE -- HOT FLASHES *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* SMALL GOITER *  0/191 (0.00%)  0 1/184 (0.54%)  1
Eye disorders     
BIL. CATARACTS *  0/191 (0.00%)  0 1/184 (0.54%)  1
BLEEDING IN EYE FROM THORN *  1/191 (0.52%)  1 0/184 (0.00%)  0
CATARACT SURGERY RIGHT EYE *  0/191 (0.00%)  0 1/184 (0.54%)  1
DRY EYE *  0/191 (0.00%)  0 1/184 (0.54%)  1
FUZZY EYESIGHT *  0/191 (0.00%)  0 1/184 (0.54%)  1
HEMIANOPSIA *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER CONJUNCTIVITIS, WITH OP EYE SURGERY *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* BLEPHARITIS *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* CONJUNCTIVITIS (ALLERGIC) *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* DRY EYES *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* EPISCLERITIS *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* FLOATER D/T DIABETIC RETINOPATHY *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* GLAUCOMA *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* GLAUCOMA INCREASED *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* ITCHY EYES *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* OCULAR - DRY MACULAR DEGENERATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* OCULAR - INCREASE INTRAOCULAR PRESSURE LEFT EYE *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* OCULAR/VISUAL MYOPIA *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* REDDENED EYES *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* RETINA EDEMA, POST OP *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* RETINAL TEAR LEFT EYE *  0/191 (0.00%)  0 1/184 (0.54%)  2
OTHER* RIGHT EYE BLURRINESS *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* SUBORBITAL EDEMA, RIGHT EYE *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* TEARY/WATERY EYES *  0/191 (0.00%)  0 1/184 (0.54%)  1
PSEDOTUMOR EYE WILL F/U IN 6 MONTHS *  0/191 (0.00%)  0 1/184 (0.54%)  1
SUBCONJUNCTIVAL HEMORRHAGE *  1/191 (0.52%)  1 0/184 (0.00%)  0
VISION *  0/191 (0.00%)  0 2/184 (1.09%)  2
VISION BLURRED *  1/191 (0.52%)  1 0/184 (0.00%)  0
VISION BLURRED RIGH EYE *  0/191 (0.00%)  0 1/184 (0.54%)  1
VISION BLURRED WHEN READING *  0/191 (0.00%)  0 1/184 (0.54%)  1
VISION BLURRING *  0/191 (0.00%)  0 1/184 (0.54%)  1
VISION CATARACT *  1/191 (0.52%)  1 0/184 (0.00%)  0
VISION CATARACT LEFT EYE *  0/191 (0.00%)  0 1/184 (0.54%)  1
VISION CATARACTS, "FLASHING LIGHT" *  1/191 (0.52%)  1 0/184 (0.00%)  0
VISION DISTURBANCE *  1/191 (0.52%)  1 0/184 (0.00%)  0
VISION FLASHING LIGHTS - BILATERAL *  0/191 (0.00%)  0 1/184 (0.54%)  1
VISION FLOATERS - LEFT EYE *  0/191 (0.00%)  0 1/184 (0.54%)  1
VISION FLOATERS, RIGHT EYE *  1/191 (0.52%)  1 0/184 (0.00%)  0
VISION GLAUCOMA *  1/191 (0.52%)  1 0/184 (0.00%)  0
VISION INCREASED INTRAOCULAR PRESSURE *  0/191 (0.00%)  0 1/184 (0.54%)  1
VISION LEFT EYE BLURRY *  0/191 (0.00%)  0 1/184 (0.54%)  1
VISION MYOPIA, LACERATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
VISION RIGHT CATARACT *  0/191 (0.00%)  0 1/184 (0.54%)  1
VISION SUB-CONJUNCTIVAL HEMMORHAGE *  1/191 (0.52%)  1 0/184 (0.00%)  0
Gastrointestinal disorders     
ABDOMINAL PAIN *  4/191 (2.09%)  6 5/184 (2.72%)  5
ABDOMINAL PAIN ABD CRAMPING AND BLOAT *  1/191 (0.52%)  1 0/184 (0.00%)  0
ABDOMINAL PAIN ABD. CRAMP AND CONSTIPATION *  1/191 (0.52%)  2 0/184 (0.00%)  0
ABDOMINAL PAIN ABDOMINAL CRAMPING *  1/191 (0.52%)  1 0/184 (0.00%)  0
ABDOMINAL PAIN CRAMPING *  2/191 (1.05%)  2 0/184 (0.00%)  0
ABDOMINAL PAIN CRAMPS/ CONSTIPATION *  1/191 (0.52%)  2 0/184 (0.00%)  0
ABDOMINAL PAIN DIARRHEA X 1-2 DAILY, CRAMPING *  1/191 (0.52%)  1 0/184 (0.00%)  0
ABDOMINAL PAIN DIARRHEA X 3-4 DAILY, CRAMPING *  1/191 (0.52%)  1 0/184 (0.00%)  0
ABDOMINAL PAIN EPIGASTRIC PAIN *  1/191 (0.52%)  1 0/184 (0.00%)  0
ABDOMINAL PAIN LEFT SIDE *  2/191 (1.05%)  2 0/184 (0.00%)  0
ABDOMINAL PAIN LOWER ABDOMEN, INTERMITTENT *  0/191 (0.00%)  0 1/184 (0.54%)  1
ABDOMINAL PAIN LOWER ABDOMINAL CRAMPING AFTER COLONOSCOPY *  0/191 (0.00%)  0 1/184 (0.54%)  1
ABDOMINAL PAIN OCCASIONAL ABD CRAMP WITH LOOSE STOOL WHEN NERVIOUS *  1/191 (0.52%)  1 0/184 (0.00%)  0
ABDOMINAL PAIN STOMACH CRAMPS *  1/191 (0.52%)  1 0/184 (0.00%)  0
ABDOMINAL PAIN UPSET STOMACH *  0/191 (0.00%)  0 1/184 (0.54%)  1
BLACK STOOLS (THINKS FROM MAALOX) *  1/191 (0.52%)  1 0/184 (0.00%)  0
BLEEDING GUMS DURING DENTAL VISIT *  0/191 (0.00%)  0 2/184 (1.09%)  2
BLEEDING RECTAL *  7/191 (3.66%)  12 5/184 (2.72%)  6
BLEEDING RECTAL 4 EPISODES BRBPR *  1/191 (0.52%)  1 0/184 (0.00%)  0
BLEEDING RECTAL BRB TOILET PAPER *  0/191 (0.00%)  0 1/184 (0.54%)  2
BLEEDING RECTAL HEMORRHOIDS *  5/191 (2.62%)  5 2/184 (1.09%)  2
BLEEDING* HEMATOCHEZIA *  0/191 (0.00%)  0 1/184 (0.54%)  1
BLEEDING* UPPER GI BLEED *  0/191 (0.00%)  0 1/184 (0.54%)  1
BLEEDING, RECTAL *  2/191 (1.05%)  2 0/184 (0.00%)  0
BLOOD IN STOOL *  4/191 (2.09%)  4 0/184 (0.00%)  0
BLOOD IN STOOL /HEMORRHOID *  1/191 (0.52%)  1 0/184 (0.00%)  0
BLOOD IN STOOL BURGUNDY *  1/191 (0.52%)  1 0/184 (0.00%)  0
BLOOD IN STOOL DIARRHEA, CRAMPING, BLACK STOOL *  0/191 (0.00%)  0 1/184 (0.54%)  1
BLOOD IN STOOL DX: COLITIS *  0/191 (0.00%)  0 1/184 (0.54%)  1
BLOOD IN STOOL OCCULT *  1/191 (0.52%)  1 0/184 (0.00%)  0
BLOOD WITH BM *  0/191 (0.00%)  0 1/184 (0.54%)  1
BOWEL MOVEMENT REGULARITY CONTINUES *  0/191 (0.00%)  0 1/184 (0.54%)  1
CONSTIPATION *  6/191 (3.14%)  8 4/184 (2.17%)  7
CONSTIPATION CHRONIC *  0/191 (0.00%)  0 1/184 (0.54%)  1
CONSTIPATION GETTING WORSE *  1/191 (0.52%)  1 0/184 (0.00%)  0
CONSTIPATION INCONTINENCE *  0/191 (0.00%)  0 1/184 (0.54%)  1
CONSTIPATION R/T IMMODIUM *  0/191 (0.00%)  0 1/184 (0.54%)  1
CRAMPING *  1/191 (0.52%)  1 0/184 (0.00%)  0
DIARRHEA *  31/191 (16.23%)  49 29/184 (15.76%)  47
DIARRHEA + ABDOMINAL CRAMPS *  1/191 (0.52%)  1 0/184 (0.00%)  0
DIARRHEA 2 EPISODES *  0/191 (0.00%)  0 1/184 (0.54%)  1
DIARRHEA 3 EPISODES *  1/191 (0.52%)  1 0/184 (0.00%)  0
DIARRHEA AFTER COLONOSCOPY *  0/191 (0.00%)  0 1/184 (0.54%)  1
DIARRHEA CONTINUED DIARRHEA *  0/191 (0.00%)  0 1/184 (0.54%)  1
DIARRHEA LOOSE STOOL *  0/191 (0.00%)  0 1/184 (0.54%)  1
DIARRHEA LOOSER STOOL *  1/191 (0.52%)  1 0/184 (0.00%)  0
DIARRHEA MILD *  1/191 (0.52%)  1 0/184 (0.00%)  0
DIARRHEA OCCASIONAL *  1/191 (0.52%)  1 1/184 (0.54%)  1
DIARRHEA X 1 RELATED TO FOOD *  1/191 (0.52%)  1 0/184 (0.00%)  0
DIVERTICULITIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
EARLY SATIETY *  0/191 (0.00%)  0 1/184 (0.54%)  1
EPIGASTRIC PAIN *  8/191 (4.19%)  8 7/184 (3.80%)  8
EPIGASTRIC PAIN 2-3 EPISODES PER WEEK *  0/191 (0.00%)  0 1/184 (0.54%)  1
EPIGASTRIC PAIN GAS PAINS *  0/191 (0.00%)  0 1/184 (0.54%)  1
EPIGASTRIC PAIN GAS X 1 PER MONTH *  0/191 (0.00%)  0 1/184 (0.54%)  1
EPIGASTRIC PAIN GASTRIC PAIN *  0/191 (0.00%)  0 1/184 (0.54%)  1
EPIGASTRIC PAIN GERD *  1/191 (0.52%)  1 1/184 (0.54%)  1
EPIGASTRIC PAIN GERD (INCREASE SYMPTOMS) *  0/191 (0.00%)  0 1/184 (0.54%)  1
EPIGASTRIC PAIN GERD, WORSENED, EST. START 1970 *  0/191 (0.00%)  0 1/184 (0.54%)  1
EPIGASTRIC PAIN PAIN X 1 *  0/191 (0.00%)  0 1/184 (0.54%)  1
EPIGASTRIC PAIN RIGHT SIDE *  0/191 (0.00%)  0 1/184 (0.54%)  1
FLATULENCE *  0/191 (0.00%)  0 1/184 (0.54%)  1
GASTRIC REFLUX *  1/191 (0.52%)  1 0/184 (0.00%)  0
GASTRITIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI ABDOMINAL BLOATING *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI BARRETT'S ESOPHAGUS *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI BARRETT'S ESOPHAGUS/DYSPLASIA *  0/191 (0.00%)  0 1/184 (0.54%)  1
GI BLOATING *  2/191 (1.05%)  2 0/184 (0.00%)  0
GI BLOATING / GAS *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI BLOATING/FEELING OF INCOMPLETE EVACUATION, CONSISTENT WITH IBS *  0/191 (0.00%)  0 1/184 (0.54%)  1
GI CECUM BIOPSY: EROSIM WITH CHRONIC INFLAMMATION, NON-SPECIFIC *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI CONT. COLITIS SX *  0/191 (0.00%)  0 1/184 (0.54%)  1
GI CONT. ESOPHAGEAL IRRITATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
GI ESOPHAGEAL FULLNESS RELATED TO GASTRO CIRCLAGE *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI HEARTBURN *  1/191 (0.52%)  1 3/184 (1.63%)  3
GI HEARTBURN 1 - 2 EPISODES/WEEK *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI HEARTBURN 4 EPISODES WEEKLY *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI HEARTBURN 5-6 EPISODES/WEEK *  0/191 (0.00%)  0 1/184 (0.54%)  1
GI HEARTBURN 5-6- EPISODES/WEEK *  0/191 (0.00%)  0 1/184 (0.54%)  1
GI HEARTBURN X9 EPISODES *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI HEARTBURN, 1 EPISODE PER WEEK *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI INCREASE IN GERD SYMPTOMS *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI INCREASED GERD SX *  0/191 (0.00%)  0 1/184 (0.54%)  1
GI INFLAMMATION COLITIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI PEPTIC ULCER DISEASE *  0/191 (0.00%)  0 1/184 (0.54%)  1
GI STOMACH CRAMPS *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI UPPER GI PAIN/ACID REFLUX *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI UPSET *  0/191 (0.00%)  0 1/184 (0.54%)  1
GI UPSET STOMACH *  0/191 (0.00%)  0 2/184 (1.09%)  3
GI UPSET STOMACH X 2 EPISODES *  1/191 (0.52%)  1 0/184 (0.00%)  0
GI UPSET STOMACH X3 EPISODES *  1/191 (0.52%)  1 0/184 (0.00%)  0
GUM SORENESS *  0/191 (0.00%)  0 1/184 (0.54%)  2
H. PYLORI +, STOMACH UPSET *  1/191 (0.52%)  1 0/184 (0.00%)  0
H.PYLORI +, DX IBS - CONSTIPATION *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEARTBURN *  1/191 (0.52%)  1 1/184 (0.54%)  2
HEMMORRHOID *  1/191 (0.52%)  1 0/184 (0.00%)  0
HEMORRHOIDS *  2/191 (1.05%)  2 3/184 (1.63%)  4
HEMORRHOIDS FLARE-UP *  0/191 (0.00%)  0 1/184 (0.54%)  1
INCREASE "BURPING" *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASE FLATULENCE *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASE FREQ OF HEMORHOIDAL BLEEDING *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASE STOOL FREQUENCY *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASE STOOLING *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASED BOWEL MOVEMENTS *  0/191 (0.00%)  0 1/184 (0.54%)  1
INCREASED FLATULENCE; ANAL INCONTINENCE *  1/191 (0.52%)  2 0/184 (0.00%)  0
INCREASED STOOLING *  0/191 (0.00%)  0 1/184 (0.54%)  1
INDIGESTION *  4/191 (2.09%)  6 3/184 (1.63%)  3
INDIGESTION DYSPEPSIA *  0/191 (0.00%)  0 1/184 (0.54%)  1
INDIGESTION EPIGASTRIC PAIN *  0/191 (0.00%)  0 1/184 (0.54%)  1
INDIGESTION HEART BURN *  1/191 (0.52%)  1 0/184 (0.00%)  0
LICHEN PLANUS MOUTH + TONGUE *  0/191 (0.00%)  0 1/184 (0.54%)  1
LLQ ABDOMINAL PAIN WITH BM *  0/191 (0.00%)  0 1/184 (0.54%)  1
LOOSE STOOL *  1/191 (0.52%)  1 2/184 (1.09%)  3
NAUSEA *  16/191 (8.38%)  18 11/184 (5.98%)  16
NAUSEA 5 EPISODES *  1/191 (0.52%)  1 0/184 (0.00%)  0
NAUSEA AFTER COLONOSCOPY *  0/191 (0.00%)  0 1/184 (0.54%)  1
NAUSEA AND BELCHING *  1/191 (0.52%)  2 0/184 (0.00%)  0
NAUSEA NAUSEA/DIARRHEA/HEADACHE *  1/191 (0.52%)  3 0/184 (0.00%)  0
NAUSEA POST SURGICAL *  1/191 (0.52%)  1 0/184 (0.00%)  0
NAUSEA RELATED TO NEW MEDICINE GLUCOPHAGE *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL HAD BUMP ON SURFACE OF TONGUE *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL SORE NEAR RIGHT INCISOR *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL SORENESS, UPPER RIGHT GUM WHERE PREVIOUSLY BAD TOOTH REMOVED *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL SORES *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* BLISTER ROOF OF MOUTH *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* CANKER SORES *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* CANKER SORES ON TONGUE *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* CHAPPED LIPS *  1/191 (0.52%)  2 0/184 (0.00%)  0
ORAL* COLD SORES, LIPS *  3/191 (1.57%)  3 0/184 (0.00%)  0
ORAL* DIFFICULTY SWALLOWING POSSIBLY DUE TO ROSACEA MEDS *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* DISCOLORING OF TEETH *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* DISCOMFORT MOUTH, POST DENTAL WORK *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* DRY MOUTH *  1/191 (0.52%)  1 1/184 (0.54%)  1
ORAL* DRY THROAT *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* DRY THROAT/MOUTH *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* DYSGEUSIA/TASTE DISTURBANCE *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* DYSPHAGIA *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* EXACERBATION/ LICHEN PLANUS *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* GINGIVITIS FROM TEETH SCALING *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* GUM PAIN *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* HYPERTROPHY, LUMP LEFT UPPER GUM *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* INCREASED SALIVA *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* INTERMITTENT ORAL ULCERS *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* LESION *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* LESION ON LOWER LIP *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* MOUTH DRYNESS *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* MOUTH SORE *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* MOUTH SORES *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* PAIN - SOFT PALATE POST SURGICAL *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* PAIN IN MOUTH POST PERIODONTAL SURGERY *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* PAIN RIGHT UPPER MOLAR *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* PRE-ABSCESS *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* SORE GUM - RIGHT *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* SORE THROAT *  0/191 (0.00%)  0 4/184 (2.17%)  5
ORAL* SORENESS *  1/191 (0.52%)  1 1/184 (0.54%)  1
ORAL* THROAT DRYNESS *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* THROAT IRRITATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* TOOTH PAIN *  0/191 (0.00%)  0 1/184 (0.54%)  1
ORAL* ULCERS *  1/191 (0.52%)  2 0/184 (0.00%)  0
OTHER* ABDOMINAL BLOATING *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* ANAL FISTULA *  1/191 (0.52%)  2 0/184 (0.00%)  0
OTHER* ANAL FISTULA, SURG REPAIR *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* BLOATING *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* BLOATING, HX IBS *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* CRAMPING *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* DIFFICULTY SWALLOWING(DYSPHAGIA) *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* DYSPEPSIA *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* DYSPHAGIA *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* ERODED ESOPHAGUS/GERD *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* ESOPHAGEAL SPASM *  1/191 (0.52%)  2 1/184 (0.54%)  1
OTHER* ESOPHAGEAL STRICTURE *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* ESOPHAGITIS *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* FOOD POISONING *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* FOOD POISONING: DIARRHEA. VOMITTING *  1/191 (0.52%)  2 0/184 (0.00%)  0
OTHER* GASTRITIS, DEHYDRATION, RESPIRATORY TRACT INFECTION, FATIGUE *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* GERD *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* HARDER STOOLS *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* HEARTBURN *  7/191 (3.66%)  15 7/184 (3.80%)  9
OTHER* HEARTBURN 2X WEEKLY *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* HEARTBURN 3 TIMES A WEEK *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* HEARTBURN X 3 EPISODES *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* HEARTBURN X5 EPISODES *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* HEARTBURN, 3-4 EPISODES/WEEK *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* HEARTBURN, INCREASE? *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* HEME + X3 *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* HT OF GASTRIC ULCERS *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* INCREASED GAS WITH EATING *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* LOOSE SPHINCTER RECTURM-SEEPAGE *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* LOOSE STOOL *  1/191 (0.52%)  1 1/184 (0.54%)  1
OTHER* MOUTH COLD SORE *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* ORAL SORENESS; ABCESS LOWER GUM *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* PERIANAL ABSCESS *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* PERIANAL SWELLING *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* RECTAL MOISTNESS *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* RECTAL URGENCY *  0/191 (0.00%)  0 1/184 (0.54%)  2
OTHER* RECTOCELE, VAGINAL *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* RIGHT INGUINAL HERNIA *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* STOMACH CRAMPING *  0/191 (0.00%)  0 1/184 (0.54%)  2
OTHER* VERY LOOSE STOOL *  0/191 (0.00%)  0 1/184 (0.54%)  4
PAIN AND LOCAL SWELLING, UPPER LEFT MOLAR *  1/191 (0.52%)  1 0/184 (0.00%)  0
PAIN* GAS *  1/191 (0.52%)  2 0/184 (0.00%)  0
PAIN* PELVIC CRAMPING *  0/191 (0.00%)  0 1/184 (0.54%)  8
PAIN* RECTAL PAIN *  0/191 (0.00%)  0 1/184 (0.54%)  1
PAIN* STOMACH *  0/191 (0.00%)  0 1/184 (0.54%)  2
PAIN* TOOTH *  1/191 (0.52%)  1 0/184 (0.00%)  0
PROCTALGIA FUGAX *  0/191 (0.00%)  0 1/184 (0.54%)  1
PROTRUDING AND TENDER HEMORRHOIDS *  1/191 (0.52%)  1 0/184 (0.00%)  0
REFLUX *  2/191 (1.05%)  2 3/184 (1.63%)  4
REFLUX ACID *  1/191 (0.52%)  1 0/184 (0.00%)  0
REFLUX ACID REFLUX *  0/191 (0.00%)  0 2/184 (1.09%)  2
REFLUX ACID REFLUX 2-3 EPISODES/WK *  0/191 (0.00%)  0 1/184 (0.54%)  1
REFLUX ACID REFLUX DAILY *  0/191 (0.00%)  0 1/184 (0.54%)  1
REFLUX GASTRIC *  0/191 (0.00%)  0 1/184 (0.54%)  1
REFLUX GERD *  1/191 (0.52%)  1 0/184 (0.00%)  0
REFLUX GERD EPISODE *  1/191 (0.52%)  2 0/184 (0.00%)  0
REFLUX GERD EPISODIC *  1/191 (0.52%)  1 0/184 (0.00%)  0
REFLUX GERD, INCREASED SEVERITY OF EPISODES *  0/191 (0.00%)  0 1/184 (0.54%)  1
REFLUX INCREASED GERD, NUMBER OF EPISODES *  1/191 (0.52%)  1 0/184 (0.00%)  0
RIGHT RENAL CYST *  0/191 (0.00%)  0 1/184 (0.54%)  1
SLIGHT QUEEZY STOMACH *  1/191 (0.52%)  1 0/184 (0.00%)  0
STOMACH ACHE *  0/191 (0.00%)  0 1/184 (0.54%)  1
STOMACH FLU *  1/191 (0.52%)  1 0/184 (0.00%)  0
STOMACH PAIN *  1/191 (0.52%)  1 0/184 (0.00%)  0
STOMACH UPSET AND HEARTBURN *  1/191 (0.52%)  2 0/184 (0.00%)  0
STOMACH VIRUS (VIRAL GASTROECTERITIS) *  1/191 (0.52%)  1 0/184 (0.00%)  0
STOOL* BLACK *  0/191 (0.00%)  0 1/184 (0.54%)  1
STOOL* CLEAR RECTAL DISCHARGE *  0/191 (0.00%)  0 1/184 (0.54%)  1
STOOL* DISCOLORED *  0/191 (0.00%)  0 1/184 (0.54%)  1
STOOL* HARD *  0/191 (0.00%)  0 1/184 (0.54%)  1
STOOL* HIGHER FREQUENCY *  1/191 (0.52%)  1 0/184 (0.00%)  0
STOOL* LOOSE *  2/191 (1.05%)  2 1/184 (0.54%)  1
STOOL* LOOSE, 2-3 DAYS/WEEK *  1/191 (0.52%)  1 0/184 (0.00%)  0
STOOL* LOOSER *  1/191 (0.52%)  1 0/184 (0.00%)  0
STOOL* SOFT WITH ABDOMINAL CRAMPS *  1/191 (0.52%)  1 0/184 (0.00%)  0
STOOL* TARRY *  1/191 (0.52%)  1 0/184 (0.00%)  0
TOOTH ABCESS *  1/191 (0.52%)  1 0/184 (0.00%)  0
TOOTH INFECTION *  0/191 (0.00%)  0 1/184 (0.54%)  1
TOOTH INFECTION -> ROOT CANAL *  1/191 (0.52%)  1 0/184 (0.00%)  0
UPPER HARD PALATE 1 CM ERYTHEMA W/ ULCER *  1/191 (0.52%)  1 0/184 (0.00%)  0
VIRAL GASTROENTERITIS *  0/191 (0.00%)  0 1/184 (0.54%)  1
VOMITING *  9/191 (4.71%)  9 5/184 (2.72%)  8
VOMITING AND NAUSEA *  0/191 (0.00%)  0 1/184 (0.54%)  1
VOMITING NAUSEA AND VOMITING *  1/191 (0.52%)  1 0/184 (0.00%)  0
VOMITTING *  0/191 (0.00%)  0 1/184 (0.54%)  1
General disorders     
BIL LE EDEMA *  1/191 (0.52%)  1 0/184 (0.00%)  0
BIL SWOLLEN FEET AND ANKLES *  1/191 (0.52%)  1 0/184 (0.00%)  0
BLEEDING* SHAVING *  0/191 (0.00%)  0 1/184 (0.54%)  1
COLD SYMPTOMS *  11/191 (5.76%)  13 9/184 (4.89%)  11
COLD SYMPTOMS COLD X3-4 *  1/191 (0.52%)  1 0/184 (0.00%)  0
COLD SYMPTOMS HEAD *  1/191 (0.52%)  1 0/184 (0.00%)  0
COLD SYMPTOMS HEAD COLD *  0/191 (0.00%)  0 6/184 (3.26%)  6
FATIGUE *  32/191 (16.75%)  34 17/184 (9.24%)  19
FATIGUE* ALLERGY FATIGUE *  0/191 (0.00%)  0 1/184 (0.54%)  1
FATIGUE* BILATERAL LEG FATIGUE *  0/191 (0.00%)  0 1/184 (0.54%)  1
FATIGUE* DIAPHORESIS AFTER MEALS *  0/191 (0.00%)  0 1/184 (0.54%)  1
FATIGUE* INCREASED *  0/191 (0.00%)  0 1/184 (0.54%)  1
FATIGUE* MILD *  0/191 (0.00%)  0 1/184 (0.54%)  1
FATIGUE* MILD DEPRESSION *  0/191 (0.00%)  0 1/184 (0.54%)  1
FATIGUE* MUSCLE ACHES *  0/191 (0.00%)  0 1/184 (0.54%)  1
FATIGUE* POSSIBLE VIRUS *  0/191 (0.00%)  0 1/184 (0.54%)  1
FATIGUE* R/T MUSCLE WEAKNESS *  0/191 (0.00%)  0 1/184 (0.54%)  1
FATIGUE* RELATED TO MUSCLE WEAKNESS *  0/191 (0.00%)  0 1/184 (0.54%)  1
FATIGUE* SYNCOPE *  1/191 (0.52%)  1 0/184 (0.00%)  0
FATIGUE* WEAKNESS *  1/191 (0.52%)  1 0/184 (0.00%)  0
FEVER *  2/191 (1.05%)  2 1/184 (0.54%)  1
FEVER INTERMITTENT *  1/191 (0.52%)  1 0/184 (0.00%)  0
FEVER SWEATS *  0/191 (0.00%)  0 1/184 (0.54%)  2
FEVER X 2DAYS *  1/191 (0.52%)  1 0/184 (0.00%)  0
FEVER X1 *  1/191 (0.52%)  1 0/184 (0.00%)  0
FLU *  7/191 (3.66%)  7 3/184 (1.63%)  3
FLU ACHY, NAUSEA, HEADACHE, COUGH *  1/191 (0.52%)  1 0/184 (0.00%)  0
FLU DIARRHEA N/V *  1/191 (0.52%)  2 0/184 (0.00%)  0
FLU FLU-LIKE SYMPTOMS *  1/191 (0.52%)  1 0/184 (0.00%)  0
FLU INFECTION *  1/191 (0.52%)  1 0/184 (0.00%)  0
FLU S/S *  0/191 (0.00%)  0 1/184 (0.54%)  1
FLU SYMPTOMS *  1/191 (0.52%)  1 1/184 (0.54%)  1
FLU X5 DAYS *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASED FATIGUE *  0/191 (0.00%)  0 1/184 (0.54%)  1
LOWGRADE FEVER *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* + + PITTING BILATERAL ANKLE EDEMA *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* BAD COLD X 3 WKS *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* BILATERAL FOOT EDEMA R>L *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* BILATERAL LOWER EXTREMEITY EDEMA *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* CHILLS, JOINT PAIN, SKIN IS SENSITIVE *  0/191 (0.00%)  0 1/184 (0.54%)  3
OTHER* EDEMA *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* EDEMA LEFT EXTREMITY *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* GENERAL ACHES *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* GENERAL BODY ACHES *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* INCREASED STRESS *  1/191 (0.52%)  1 2/184 (1.09%)  2
OTHER* LETHARGY *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* LOWER EXTREMITY EDEMA *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* LOWER EXTREMITY EDEMA - BILATERAL *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* SLEEPY *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* STRESS, INCREASED *  0/191 (0.00%)  0 1/184 (0.54%)  1
PAIN *  1/191 (0.52%)  1 0/184 (0.00%)  0
SWELLING PERIPHERAL EDEMA *  1/191 (0.52%)  1 0/184 (0.00%)  0
SWOLLEN ANKLES (PERIPHERAL EDEMA) *  1/191 (0.52%)  1 0/184 (0.00%)  0
Hepatobiliary disorders     
OTHER* GALLSTONES *  0/191 (0.00%)  0 1/184 (0.54%)  1
Immune system disorders     
OTHER* URTICARIA *  0/191 (0.00%)  0 1/184 (0.54%)  1
Infections and infestations     
BLEEDING* GUMS *  0/191 (0.00%)  0 1/184 (0.54%)  1
BROKEN TOOTH *  1/191 (0.52%)  1 0/184 (0.00%)  0
FEVER BLISTERS *  0/191 (0.00%)  0 1/184 (0.54%)  1
HERPES *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASED ORAL HERPES OUTBREAKS *  0/191 (0.00%)  0 1/184 (0.54%)  1
INFECTION* BLADDER *  0/191 (0.00%)  0 2/184 (1.09%)  2
INFECTION* BLADDER INFECTION *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* EAR *  0/191 (0.00%)  0 2/184 (1.09%)  2
INFECTION* ESOPHAGITIS *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* EUSTACHIAN TUBES *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* FUNGAL FINGERNAIL *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* FUNGAL INFECTION FINGERNAILS *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* FUNGAL, LEFT MIDDLE FINGER *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* INFECTED SCROTAL CYST *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* INSECT BITE RIGHT ANKLE *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* LEFT INDEX FINGER *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* LEFT LOWER LEG AK SITE *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* LEFT TESTICLE *  0/191 (0.00%)  0 1/184 (0.54%)  1
INFECTION* MIDDLE EAR-BLOCKED EUSTACHIAN TUBE *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* PNEUMONIA POSS "SCAR" ON CXR *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* RIGHT BREAST *  0/191 (0.00%)  0 1/184 (0.54%)  1
INFECTION* RIGHT CALF BITE *  0/191 (0.00%)  0 1/184 (0.54%)  2
INFECTION* RIGHT MIDDLE FINGER NAIL *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* SINUS *  3/191 (1.57%)  4 0/184 (0.00%)  0
INFECTION* SINUS INFECTION *  1/191 (0.52%)  1 0/184 (0.00%)  0
INFECTION* SKIN FUNGAL *  0/191 (0.00%)  0 1/184 (0.54%)  1
INFECTION* TOOTH *  2/191 (1.05%)  2 1/184 (0.54%)  2
INFECTION* UPPER RESPIRATORY *  0/191 (0.00%)  0 1/184 (0.54%)  1
INFECTION* VAGINAL YEAST *  1/191 (0.52%)  1 1/184 (0.54%)  1
INFECTION* WOUND/INFECTION LEFT LE *  0/191 (0.00%)  0 1/184 (0.54%)  1
INFECTION* YEAST *  1/191 (0.52%)  1 0/184 (0.00%)  0
ORAL* YEAST INFECTION *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* HSV OUTBREAK *  1/191 (0.52%)  2 0/184 (0.00%)  0
POSSIBLE FUNGAL INFECTION (SCALP) *  0/191 (0.00%)  0 1/184 (0.54%)  1
TOE INFECTION *  0/191 (0.00%)  0 1/184 (0.54%)  2
Injury, poisoning and procedural complications     
CUT SHIN = INFECTION (CELLULITIS) *  0/191 (0.00%)  0 1/184 (0.54%)  1
FINGER LACERATION RIGHT HAND *  1/191 (0.52%)  1 0/184 (0.00%)  0
FOOT CONTUSION *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* CUTS TAKE LONGER TO HEAL *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* LACERATION, ER VISIT *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* MECHANICAL FALL WITH LACERATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
OTHER* PHLEBITIS LEFT FOREARM *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* PHLEBITIS SUPERFICIAL LEFT FOREARM *  1/191 (0.52%)  1 0/184 (0.00%)  0
OTHER* SPIDER BITE (LEG) SWELLING *  1/191 (0.52%)  1 0/184 (0.00%)  0
PAIN* SCORPION BITE RIGHT FOREARM *  1/191 (0.52%)  1 0/184 (0.00%)  0
PAIN* SHIN LACERATION *  1/191 (0.52%)  1 0/184 (0.00%)  0
PAIN* STERNAL PAIN/BURNING SENSATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
WOUND INFECT *  1/191 (0.52%)  1 0/184 (0.00%)  0
WOUND* FACIAL CUT FROM FALL *  0/191 (0.00%)  0 1/184 (0.54%)  1
WOUND* HEAD LACERATION *  0/191 (0.00%)  0 1/184 (0.54%)  1
WOUND* HEAD LACERATION ON SCALP *  0/191 (0.00%)  0 1/184 (0.54%)  1
Investigations     
5 LBS X 2 WKS *  0/191 (0.00%)  0 1/184 (0.54%)  1
ABNORMAL X-RAY *  1/191 (0.52%)  1 0/184 (0.00%)  0
DECREASE HGB 5% FROM BASELINE *  0/191 (0.00%)  0 1/184 (0.54%)  1
DECREASE IN HGB *  0/191 (0.00%)  0 1/184 (0.54%)  1
DROP HGB *  0/191 (0.00%)  0 1/184 (0.54%)  1
DROP IN HGB *  0/191 (0.00%)  0 1/184 (0.54%)  1
ELECT. BALANCE *  1/191 (0.52%)  1 0/184 (0.00%)  0
ELEVATED CREATININE BUN *  1/191 (0.52%)  2 0/184 (0.00%)  0
ELEVATED LIVER ENZYMES *  0/191 (0.00%)  0 1/184 (0.54%)  1
ELEVATED PSA *  0/191 (0.00%)  0 1/184 (0.54%)  1
ELEVATED TRIGLYCERIDE *  0/191 (0.00%)  0 1/184 (0.54%)  1
ELEVATED TRIGLYCERIDES 571 *  0/191 (0.00%)  0 1/184 (0.54%)  1
ELEVATED TRIGLYCERIDES 779 *  0/191 (0.00%)  0 1/184 (0.54%)  1
HYPERGLICEMIA *  1/191 (0.52%)  2 0/184 (0.00%)  0
HYPERGLYCEMIA *  1/191 (0.52%)  1 2/184 (1.09%)  2
HYPERKALEMIA *  2/191 (1.05%)  2 0/184 (0.00%)  0
INCREASED ALKPHOSPHATASE *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASED ALT *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASED AST *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASED BILIRUBIN *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASED CREATININE *  1/191 (0.52%)  1 0/184 (0.00%)  0
INCREASED HEMOGLOBIN *  0/191 (0.00%)  0 1/184 (0.54%)  1
INCREASED LFTS *  0/191 (0.00%)  0