Trial Outcomes & Findings for Efficacy of Amitriptyline for Painful Bladder Syndrome (PBS) (NCT NCT00124306)

NCT ID: NCT00124306

Last Updated: 2026-01-12

Results Overview

The primary efficacy analysis was based on intent to treat, comparing the proportion of responders between treatment arms on a patient reported GRA recorded at 12 weeks or study withdrawal. The 7-point GRA queried, "As compared to when you started the current study, how would you rate your overall symptoms now?" The 7 response options were markedly worse, moderately worse, slightly worse, the same, slightly improved, moderately improved and markedly improved. Participants who indicated that they were markedly or moderately improved were considered responders. Subjects who withdrew from the study for any reason and did not provide data on the primary outcome were considered treatment failures, and were included in the denominator for calculation of response rates.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 271 participants
• Primary outcome timeframe: 12 Weeks
• Results posted on: 2026-01-12

Participant Flow

Participant milestones

Measure	1 - Active Comparator Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily. Amitriptyline: Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.	2 - Placebo Comparator Placebo will be dosed exactly as the active arm and taken once daily. Placebo: Placebo will be dosed exactly as active arm.
Overall Study STARTED	135	136
Overall Study COMPLETED	112	119
Overall Study NOT COMPLETED	23	17

Reasons for withdrawal

Measure	1 - Active Comparator Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily. Amitriptyline: Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.	2 - Placebo Comparator Placebo will be dosed exactly as the active arm and taken once daily. Placebo: Placebo will be dosed exactly as active arm.
Overall Study Adverse Event	7	2
Overall Study Lost to Follow-up	10	6
Overall Study Lack of Efficacy	3	6
Overall Study Personal constraints	0	2
Overall Study Use of unacceptable medication	1	0
Overall Study Abnormal lab result	0	1
Overall Study Other	2	0

Baseline Characteristics

Efficacy of Amitriptyline for Painful Bladder Syndrome (PBS)

Baseline characteristics by cohort

Measure	1 - Active Comparator n=135 Participants Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily. Amitriptyline: Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.	2 - Placebo Comparator n=136 Participants Placebo will be dosed exactly as the active arm and taken once daily. Placebo: Placebo will be dosed exactly as active arm.	Total n=271 Participants Total of all reporting groups
Age, Continuous	38.0 years STANDARD_DEVIATION 13.8 • n=210 Participants	39.9 years STANDARD_DEVIATION 14.0 • n=19 Participants	39.0 years STANDARD_DEVIATION 13.9 • n=8 Participants
Sex: Female, Male Female	115 Participants n=210 Participants	111 Participants n=19 Participants	226 Participants n=8 Participants
Sex: Female, Male Male	20 Participants n=210 Participants	25 Participants n=19 Participants	45 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=210 Participants	0 Participants n=19 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=210 Participants	0 Participants n=19 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=210 Participants	0 Participants n=19 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	18 Participants n=210 Participants	15 Participants n=19 Participants	33 Participants n=8 Participants
Race (NIH/OMB) White	96 Participants n=210 Participants	104 Participants n=19 Participants	200 Participants n=8 Participants
Race (NIH/OMB) More than one race	21 Participants n=210 Participants	17 Participants n=19 Participants	38 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=210 Participants	0 Participants n=19 Participants	0 Participants n=8 Participants
Participants ever diagnosed with IC/PBS	62 Participants n=210 Participants	75 Participants n=19 Participants	137 Participants n=8 Participants
Pain score	5.8 units on a scale STANDARD_DEVIATION 1.5 • n=210 Participants	6.0 units on a scale STANDARD_DEVIATION 1.8 • n=19 Participants	5.9 units on a scale STANDARD_DEVIATION 1.7 • n=8 Participants
Urgency score	6.4 units on a scale STANDARD_DEVIATION 1.8 • n=210 Participants	6.4 units on a scale STANDARD_DEVIATION 1.8 • n=19 Participants	6.4 units on a scale STANDARD_DEVIATION 1.8 • n=8 Participants
Frequency score	6.8 units on a scale STANDARD_DEVIATION 1.7 • n=210 Participants	6.8 units on a scale STANDARD_DEVIATION 1.8 • n=19 Participants	6.8 units on a scale STANDARD_DEVIATION 1.8 • n=8 Participants
24-Hr voiding frequency	13.9 Voiding events STANDARD_DEVIATION 5.2 • n=210 Participants	13.7 Voiding events STANDARD_DEVIATION 5.7 • n=19 Participants	13.8 Voiding events STANDARD_DEVIATION 5.5 • n=8 Participants
Nighttime voiding frequency	2.4 Voiding events STANDARD_DEVIATION 1.8 • n=210 Participants	3.0 Voiding events STANDARD_DEVIATION 2.8 • n=19 Participants	2.7 Voiding events STANDARD_DEVIATION 2.3 • n=8 Participants
Interstitial Cystitis Symptom Index	12.2 units on a scale STANDARD_DEVIATION 3.1 • n=210 Participants	12.0 units on a scale STANDARD_DEVIATION 3.6 • n=19 Participants	12.1 units on a scale STANDARD_DEVIATION 3.4 • n=8 Participants
Interstitial Cystitis Problem Index	11.1 units on a scale STANDARD_DEVIATION 2.8 • n=210 Participants	11.2 units on a scale STANDARD_DEVIATION 3.0 • n=19 Participants	11.2 units on a scale STANDARD_DEVIATION 2.9 • n=8 Participants
University of Wisconsin Symptom Inventory	25.9 units on a scale STANDARD_DEVIATION 8.6 • n=210 Participants	26.7 units on a scale STANDARD_DEVIATION 8.3 • n=19 Participants	26.3 units on a scale STANDARD_DEVIATION 8.5 • n=8 Participants

PRIMARY outcome

Timeframe: 12 Weeks

The primary efficacy analysis was based on intent to treat, comparing the proportion of responders between treatment arms on a patient reported GRA recorded at 12 weeks or study withdrawal. The 7-point GRA queried, "As compared to when you started the current study, how would you rate your overall symptoms now?" The 7 response options were markedly worse, moderately worse, slightly worse, the same, slightly improved, moderately improved and markedly improved. Participants who indicated that they were markedly or moderately improved were considered responders. Subjects who withdrew from the study for any reason and did not provide data on the primary outcome were considered treatment failures, and were included in the denominator for calculation of response rates.

Outcome measures

Measure	1 - Active Comparator n=135 Participants Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily. Amitriptyline: Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.	2 - Placebo Comparator n=136 Participants Placebo will be dosed exactly as the active arm and taken once daily. Placebo: Placebo will be dosed exactly as active arm.
Global Response Assessment (GRA) Marked/moderate improvement	74 Participants	61 Participants
Global Response Assessment (GRA) Slight improvement, same or worse	61 Participants	75 Participants

SECONDARY outcome

Timeframe: Baseline and 12 Weeks

A number of secondary outcomes [as detailed in the Baseline Measures section] were assessed throughout the study. These outcomes include pain, urgency and frequency on 0 to 10-point Likert scales, a 24-hour voiding diary, the Health Status Questionnaire for Quality of Life (SF-36), the Hospital Anxiety and Depression Scale, and the Female Sexual Function Index or International Index of Erectile Function. When applicable, additional analyses of the symptom outcomes may include evaluation of secondary response rates defined by specific changes in symptoms. Associations between changes from baseline in secondary outcomes and GRA will be used to supplement the primary endpoint analysis, and to evaluate the validity of the symptom scales for assessing change.

Outcome measures

Measure	1 - Active Comparator n=135 Participants Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily. Amitriptyline: Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.	2 - Placebo Comparator n=136 Participants Placebo will be dosed exactly as the active arm and taken once daily. Placebo: Placebo will be dosed exactly as active arm.
Changes in Quality of Life Measures From Baseline to 12 Weeks Pain score	-2.6 Change in score baseline to 12 weeks Standard Deviation 2.5	-2.3 Change in score baseline to 12 weeks Standard Deviation 2.4
Changes in Quality of Life Measures From Baseline to 12 Weeks Urgency	-3.0 Change in score baseline to 12 weeks Standard Deviation 2.5	-2.5 Change in score baseline to 12 weeks Standard Deviation 2.6
Changes in Quality of Life Measures From Baseline to 12 Weeks Frequency	-3.5 Change in score baseline to 12 weeks Standard Deviation 2.3	-2.6 Change in score baseline to 12 weeks Standard Deviation 2.5
Changes in Quality of Life Measures From Baseline to 12 Weeks 24-Hr voiding frequency	-4.4 Change in score baseline to 12 weeks Standard Deviation 5.4	-2.0 Change in score baseline to 12 weeks Standard Deviation 3.9

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Change between the Baseline and 12-week time points is reported for each measure.

The O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices, and the University of Wisconsin Interstitial Cystitis Symptom Inventory The IC Symptom Index is a 4-question survey w/ a severity scale from min.0(not at all) to max.5(always).

The IC Problem Index is a 4-question survey with a severity scale ranging from min.0 (no problem) to max.4 (big problem).

Higher subscale responses for each index indicate more severe symptoms. A sub-set of the University of Wisconsin Symptom Survey is designated as the Interstitial Cystitis Symptom Inventory w/ questions ranging from 0(not at all) to 6(a lot). Pts. reported symptoms the day of assessment.

Scores ranged from 0 to 42. A higher score indicates more severe symptoms. Symptoms include: bladder pain; bladder discomfort; getting up at night to go to the bathroom; going to the bathroom frequently during the day; urgency to urinate; difficulty sleeping because of bladder problems; and burning sensation in the bladder.

Outcome measures

Measure	1 - Active Comparator n=135 Participants Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily. Amitriptyline: Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.	2 - Placebo Comparator n=136 Participants Placebo will be dosed exactly as the active arm and taken once daily. Placebo: Placebo will be dosed exactly as active arm.
Change in Urinary Symptoms Measures IC Symptom Index	-4.8 Change in score baseline to 12 weeks Standard Deviation 3.7	-3.3 Change in score baseline to 12 weeks Standard Deviation 3.9
Change in Urinary Symptoms Measures IC Problem Index	-5.2 Change in score baseline to 12 weeks Standard Deviation 3.9	-3.9 Change in score baseline to 12 weeks Standard Deviation 4.0
Change in Urinary Symptoms Measures Wisconsin Symptom Survey	-13.1 Change in score baseline to 12 weeks Standard Deviation 10.2	-9.3 Change in score baseline to 12 weeks Standard Deviation 9.3

SECONDARY outcome

Timeframe: 12 weeks

Population: Consistent with intent to treat analytic strategies participants who did not provide data at 12 weeks, including 24 (18%) on amitriptyline and 17 (13%) on placebo, were considered treatment non-responders.

Adherence to protocol treatment, to study drug and EBMP, at 6 weeks was assessed in 4 categories of 1) symptom management, 2) fluid management, 3) diet modification and 4) bladder training. For each of these EBMP categories adherence was defined as the overall percentage of participants who reported adhering to each component of the EBMP at each telephone contact or clinic visit. Subjects were classified into 3 groups based on the maximum dose obtained at 6 and 12 weeks as shown in the Outcome Measure Data Table below.

Outcome measures

Measure	1 - Active Comparator n=135 Participants Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily. Amitriptyline: Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.	2 - Placebo Comparator n=136 Participants Placebo will be dosed exactly as the active arm and taken once daily. Placebo: Placebo will be dosed exactly as active arm.
Adherence to Study Drug and Urinary Educational/Behavioral Program (EBMP Educational/Behavioral Modification Program) 50 mg or > achieved/maintained @ 12 wks	62 Participants	98 Participants
Adherence to Study Drug and Urinary Educational/Behavioral Program (EBMP Educational/Behavioral Modification Program) 50 mg or > achieved, reduced < 50 by 12 wks	27 Participants	20 Participants
Adherence to Study Drug and Urinary Educational/Behavioral Program (EBMP Educational/Behavioral Modification Program) 50 mg or greater not achieved	46 Participants	18 Participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Changes in nighttime voids from baseline to 12 weeks were reported by treatment arm for those with available data at those points. Nighttime \[sleep period\] voiding frequency was collected by participant report on a Voiding Diary with entries for each void in a 24-hour period. Each void entry included the question: "Did this void occur during your intended sleep period?" Responses: 1=Yes, 0=No. The sum was totaled for "Yes" entries in response to this question.

Baseline nighttime [sleep period] voiding frequency was collected by participant report on a Voiding Diary with entries for each void in a 24-hour period. Each void entry included the question: "Did this void occur during your intended sleep period?" Responses: 1=Yes, 0=No. The sum was totaled for "Yes" entries in response to this question.

Outcome measures

Measure	1 - Active Comparator n=135 Participants Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily. Amitriptyline: Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.	2 - Placebo Comparator n=136 Participants Placebo will be dosed exactly as the active arm and taken once daily. Placebo: Placebo will be dosed exactly as active arm.
Change in Nighttime Voiding From Baseline to 12 Weeks	-0.9 Change in voiding events Standard Deviation 2.4	-0.9 Change in voiding events Standard Deviation 2.4

Adverse Events

1 - Amitriptyline

Serious events: 2 serious events

Other events: 119 other events

Deaths: 0 deaths

2 - Placebo

Serious events: 3 serious events

Other events: 98 other events

Deaths: 0 deaths

Serious adverse events

Measure	1 - Amitriptyline n=135 participants at risk Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily for a total of 12 weeks. Amitriptyline: Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.	2 - Placebo n=136 participants at risk Placebo will be dosed exactly as the active arm and taken once daily for a total of 12 weeks. Placebo: Placebo will be dosed exactly as active arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive transitional cell carcinoma	0.74% 1/135 • Number of events 1 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	0.00% 0/136 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Endocrine disorders Hypothyroidism	0.74% 1/135 • Number of events 1 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	0.00% 0/136 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Respiratory, thoracic and mediastinal disorders Mass found on chest x-ray	0.00% 0/135 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	0.74% 1/136 • Number of events 1 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Cardiac disorders Sudden onset of nausea, abdominal pain, SOB, subscapular pain w/left arm radiation	0.00% 0/135 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	0.74% 1/136 • Number of events 1 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Renal and urinary disorders Diagnosed with prostate cancer	0.00% 0/135 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	0.74% 1/136 • Number of events 1 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.

Other adverse events

Measure	1 - Amitriptyline n=135 participants at risk Amitryptiline, increased during a 6-week period from 10 mg up to 75 mg, taken once daily for a total of 12 weeks. Amitriptyline: Amitriptyline will be titrated over a 6-week period as tolerated, to a maximum dose of 75mg. During the 6-week titration period, the patient who cannot tolerate a scheduled increased dose may adjust the medication dose for tolerance by tapering down one 25mg tablet.	2 - Placebo n=136 participants at risk Placebo will be dosed exactly as the active arm and taken once daily for a total of 12 weeks. Placebo: Placebo will be dosed exactly as active arm.
Skin and subcutaneous tissue disorders Dermatology/skin	6.7% 9/135 • Number of events 9 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	7.4% 10/136 • Number of events 10 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
General disorders Gastrointestinal	42.2% 57/135 • Number of events 57 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	23.5% 32/136 • Number of events 32 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
General disorders Constitutional symptoms	45.2% 61/135 • Number of events 61 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	30.9% 42/136 • Number of events 42 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Infections and infestations Infection, fever	6.7% 9/135 • Number of events 9 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	10.3% 14/136 • Number of events 14 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Musculoskeletal and connective tissue disorders Musculokeletal	5.2% 7/135 • Number of events 7 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	2.2% 3/136 • Number of events 3 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Ear and labyrinth disorders Neurological	33.3% 45/135 • Number of events 45 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	21.3% 29/136 • Number of events 29 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Eye disorders Ocular, visual	2.2% 3/135 • Number of events 3 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	5.1% 7/136 • Number of events 7 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Nervous system disorders Pain	31.9% 43/135 • Number of events 43 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	35.3% 48/136 • Number of events 48 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Respiratory, thoracic and mediastinal disorders Pulmonary	11.1% 15/135 • Number of events 15 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	9.6% 13/136 • Number of events 13 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.
Renal and urinary disorders Genitourinary	16.3% 22/135 • Number of events 22 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.	7.4% 10/136 • Number of events 10 • 12 weeks Final Adverse Event reporting included all adverse events by type, regardless of their relationship to study drug. Patients are counted once in each category and included in the column relating to their worst toxicity grade. Patients may have had events in more than one body system category. An adverse event is not counted if the same event is observed at baseline with an equal or greater toxicity grade.

Additional Information

J. Richard Landis, PhD

University of Pennsylvania

Phone: 215-5734922

Email: hultman@upenn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place