Trial Outcomes & Findings for Zoledronate in Preventing Skeletal (Bone)-Related Events in Men Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases (NCT NCT00079001)

NCT ID: NCT00079001

Last Updated: 2020-05-12

Results Overview

Time to first skeletal related event (SRE) was defined as the time from randomization to first skeletal event. Skeletal events are defined as radiation to bone, clinical fracture, surgery to bone and spinal cord compression and death due to prostate cancer. The median with 95% CI was estimated using the Kaplan Meier method.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 645 participants
• Primary outcome timeframe: Up to 10 years
• Results posted on: 2020-05-12

Participant Flow

Between January 2004 and May 2012, 645 participants were registered and randomized.

Participant milestones

Measure	Zoledronic Acid + Androgen Deprivation Therapy 4mg by IV over 15 minutes every 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progression on blinded treatment before having a skeletal event may continue on open label Zoledronic acid (4 mg by IV over 15 minutes every 3 weeks).	Placebo + Androgen Deprivation Therapy Placebo bu IV over 15 minutes for 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progress on blinded treatment before having a skeletal event may continue on open label Zoledronic acid.
Overall Study STARTED	323	322
Overall Study COMPLETED	323	322
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Zoledronate in Preventing Skeletal (Bone)-Related Events in Men Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases

Baseline characteristics by cohort

Measure	Zoledronic Acid + Androgen Deprivation Therapy n=323 Participants 4mg by IV over 15 minutes every 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progression on blinded treatment before having a skeletal event may continue on open label Zoledronic acid (4 mg by IV over 15 minutes every 3 weeks).	Placebo + Androgen Deprivation Therapy n=322 Participants Placebo bu IV over 15 minutes for 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progress on blinded treatment before having a skeletal event may continue on open label Zoledronic acid.	Total n=645 Participants Total of all reporting groups
Age, Continuous	66.1 years n=5 Participants	66.7 years n=7 Participants	66.3 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	323 Participants n=5 Participants	322 Participants n=7 Participants	645 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	42 Participants n=5 Participants	50 Participants n=7 Participants	92 Participants n=5 Participants
Race (NIH/OMB) White	261 Participants n=5 Participants	256 Participants n=7 Participants	517 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment United States	323 participants n=5 Participants	321 participants n=7 Participants	644 participants n=5 Participants
Region of Enrollment Canada	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
ECOG Performance Status 0	205 participants n=5 Participants	205 participants n=7 Participants	410 participants n=5 Participants
ECOG Performance Status 1	105 participants n=5 Participants	105 participants n=7 Participants	210 participants n=5 Participants
ECOG Performance Status 2	13 participants n=5 Participants	12 participants n=7 Participants	25 participants n=5 Participants
Prior Skeletal Related Event Yes	42 participants n=5 Participants	40 participants n=7 Participants	82 participants n=5 Participants
Prior Skeletal Related Event No	281 participants n=5 Participants	282 participants n=7 Participants	563 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 10 years

Time to first skeletal related event (SRE) was defined as the time from randomization to first skeletal event. Skeletal events are defined as radiation to bone, clinical fracture, surgery to bone and spinal cord compression and death due to prostate cancer. The median with 95% CI was estimated using the Kaplan Meier method.

Outcome measures

Measure	Zoledronic Acid + Androgen Deprivation Therapy n=323 Participants 4mg by IV over 15 minutes every 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progression on blinded treatment before having a skeletal event may continue on open label Zoledronic acid (4 mg by IV over 15 minutes every 3 weeks).	Placebo + Androgen Deprivation Therapy n=322 Participants Placebo bu IV over 15 minutes for 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progress on blinded treatment before having a skeletal event may continue on open label Zoledronic acid.
Time to First Skeletal Related Event	31.9 months Interval 24.2 to 40.3	28.8 months Interval 25.3 to 37.2

SECONDARY outcome

Timeframe: Up to 10 years

Overall survival (OS) was defined as the time from randomization to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.

Outcome measures

Measure	Zoledronic Acid + Androgen Deprivation Therapy n=323 Participants 4mg by IV over 15 minutes every 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progression on blinded treatment before having a skeletal event may continue on open label Zoledronic acid (4 mg by IV over 15 minutes every 3 weeks).	Placebo + Androgen Deprivation Therapy n=322 Participants Placebo bu IV over 15 minutes for 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progress on blinded treatment before having a skeletal event may continue on open label Zoledronic acid.
Overall Survival	37.9 months Interval 34.2 to 49.2	36.0 months Interval 30.2 to 41.6

SECONDARY outcome

Timeframe: Up to 10 years

Progression Free Survival (PFS) was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method.

Progression is defined as one or more of the following: new bone metastases, biochemical progression of PSA, treatment with radiation therapy while on treatment.

Outcome measures

Measure	Zoledronic Acid + Androgen Deprivation Therapy n=323 Participants 4mg by IV over 15 minutes every 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progression on blinded treatment before having a skeletal event may continue on open label Zoledronic acid (4 mg by IV over 15 minutes every 3 weeks).	Placebo + Androgen Deprivation Therapy n=322 Participants Placebo bu IV over 15 minutes for 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progress on blinded treatment before having a skeletal event may continue on open label Zoledronic acid.
Progression-free Survival	10.6 months Interval 8.5 to 15.4	9.2 months Interval 8.0 to 11.9

Adverse Events

Zoledronic Acid + Androgen Deprivation Therapy

Serious events: 60 serious events

Other events: 269 other events

Deaths: 0 deaths

Placebo + Androgen Deprivation Therapy

Serious events: 61 serious events

Other events: 266 other events

Deaths: 0 deaths

Serious adverse events

Measure	Zoledronic Acid + Androgen Deprivation Therapy n=310 participants at risk 4mg by IV over 15 minutes every 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progression on blinded treatment before having a skeletal event may continue on open label Zoledronic acid (4 mg by IV over 15 minutes every 3 weeks).	Placebo + Androgen Deprivation Therapy n=308 participants at risk Placebo bu IV over 15 minutes for 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progress on blinded treatment before having a skeletal event may continue on open label Zoledronic acid.
Reproductive system and breast disorders Erectile dysfunction	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Reproductive system and breast disorders Pelvic pain	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Blood and lymphatic system disorders Blood disorder	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Blood and lymphatic system disorders Hemoglobin decreased	2.3% 7/310 • Number of events 9 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.9% 6/308 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Blood and lymphatic system disorders Hemolysis	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Arrhythmia supraventricular	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Atrial fibrillation	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Cardiac disorder	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Cardiac pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Left ventricular dysfunction	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Myocardial ischemia	1.6% 5/310 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Sick sinus syndrome	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Sinus tachycardia	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Supraventricular tachycardia	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Endocrine disorders Endocrine disorder	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Endocrine disorders Hyperthyroidism	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Eye disorders Vision blurred	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Abdominal distension	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Abdominal pain	1.3% 4/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Colitis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Colonic obstruction	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Constipation	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Diarrhea	3.2% 10/310 • Number of events 10 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	2.3% 7/308 • Number of events 7 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Esophageal pain	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Gastric hemorrhage	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Gastric ulcer	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Intra-abdominal hemorrhage	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Nausea	4.5% 14/310 • Number of events 14 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	5.8% 18/308 • Number of events 21 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Rectal pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Small intestinal obstruction	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Vomiting	3.2% 10/310 • Number of events 10 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	4.5% 14/308 • Number of events 16 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Chest pain	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Chills	1.6% 5/310 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Death NOS	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Disease progression	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Edema limbs	0.32% 1/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Fatigue	10.6% 33/310 • Number of events 39 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	10.4% 32/308 • Number of events 42 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Fever	1.6% 5/310 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.6% 5/308 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders General symptom	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Pain	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Sudden death	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Bladder infection	0.65% 2/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Catheter related infection	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Infection	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Infectious colitis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Pelvic infection	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Pneumonia	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Sepsis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Soft tissue infection	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Upper respiratory infection	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Urethral infection	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Urinary tract infection	1.3% 4/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Injury, poisoning and procedural complications Fracture	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Alanine aminotransferase increased	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Alkaline phosphatase increased	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Aspartate aminotransferase increased	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations CD4 lymphocytes decreased	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Coagulopathy	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Creatinine increased	7.1% 22/310 • Number of events 25 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	5.8% 18/308 • Number of events 19 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations INR increased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Laboratory test abnormal	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Leukocyte count decreased	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Lymphocyte count decreased	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Neutrophil count decreased	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Platelet count decreased	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Weight loss	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Acidosis	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Anorexia	5.2% 16/310 • Number of events 18 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	5.8% 18/308 • Number of events 21 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Blood bicarbonate decreased	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Blood glucose increased	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Blood uric acid increased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Dehydration	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.9% 6/308 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum albumin decreased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum calcium decreased	5.8% 18/310 • Number of events 21 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	5.8% 18/308 • Number of events 21 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum glucose decreased	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum magnesium decreased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.9% 6/308 • Number of events 7 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum magnesium increased	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum phosphate decreased	3.2% 10/310 • Number of events 11 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	2.6% 8/308 • Number of events 8 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum potassium decreased	5.2% 16/310 • Number of events 16 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	2.9% 9/308 • Number of events 10 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum potassium increased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum sodium decreased	1.3% 4/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Back pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.9% 6/308 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Bone pain	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.9% 6/308 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Muscle weakness	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	1.3% 4/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Myalgia	4.2% 13/310 • Number of events 18 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	7.1% 22/308 • Number of events 27 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Neck pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.97% 3/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain (onset or exacerbation of tumor pain due to treatment)	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Depressed level of consciousness	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Dizziness	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Headache	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Intracranial hemorrhage	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Ischemia cerebrovascular	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Memory impairment	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Neurological disorder NOS	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Oculomotor nerve disorder	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Peripheral motor neuropathy	0.97% 3/310 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Peripheral sensory neuropathy	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Syncope	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Syncope vasovagal	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Psychiatric disorders Agitation	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Psychiatric disorders Confusion	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Psychiatric disorders Depression	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Bladder hemorrhage	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Bladder obstruction	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Cystitis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Kidney pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Renal failure	1.6% 5/310 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Ureteric obstruction	0.97% 3/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Ureteric perforation	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Ureteric stenosis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Urethral obstruction	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Urinary incontinence	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Urinary retention	2.3% 7/310 • Number of events 7 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.97% 3/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.6% 5/308 • Number of events 7 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.32% 1/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Skin and subcutaneous tissue disorders Pruritus	1.3% 4/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Skin and subcutaneous tissue disorders Rash desquamating	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.3% 4/308 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Vascular disorders Hypertension	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Vascular disorders Hypotension	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Vascular disorders Thrombosis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.3% 4/308 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Vascular disorders Vascular disorder	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.

Other adverse events

Measure	Zoledronic Acid + Androgen Deprivation Therapy n=310 participants at risk 4mg by IV over 15 minutes every 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progression on blinded treatment before having a skeletal event may continue on open label Zoledronic acid (4 mg by IV over 15 minutes every 3 weeks).	Placebo + Androgen Deprivation Therapy n=308 participants at risk Placebo bu IV over 15 minutes for 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progress on blinded treatment before having a skeletal event may continue on open label Zoledronic acid.
Investigations CD4 lymphocytes decreased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Creatinine increased	24.8% 77/310 • Number of events 299 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	21.1% 65/308 • Number of events 316 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Laboratory test abnormal	0.97% 3/310 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Leukocyte count decreased	1.9% 6/310 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Lipase increased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Lymphocyte count decreased	0.65% 2/310 • Number of events 8 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Neutrophil count decreased	1.3% 4/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Platelet count decreased	0.32% 1/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Weight gain	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Weight loss	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Anorexia	17.4% 54/310 • Number of events 128 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	18.8% 58/308 • Number of events 128 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Blood bicarbonate decreased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Blood glucose increased	4.2% 13/310 • Number of events 23 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	3.6% 11/308 • Number of events 25 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Dehydration	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum albumin decreased	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 7 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum calcium decreased	19.0% 59/310 • Number of events 109 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	18.2% 56/308 • Number of events 113 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum glucose decreased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Skin infection	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Tooth infection	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Urinary tract infection	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Wound infection	0.32% 1/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Injury, poisoning and procedural complications Fracture	0.32% 1/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Injury, poisoning and procedural complications Venous injury - Extremity-upper	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Alanine aminotransferase increased	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Alkaline phosphatase increased	5.2% 16/310 • Number of events 25 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	4.2% 13/308 • Number of events 21 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Investigations Aspartate aminotransferase increased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Blood and lymphatic system disorders Hemoglobin decreased	2.6% 8/310 • Number of events 14 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.9% 6/308 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Blood and lymphatic system disorders Hemolysis	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Atrial fibrillation	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Atrial flutter	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Atrial tachycardia	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Cardiac disorder	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Cardiac valve disease	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Cardiopulmonary arrest	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Edema	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Left ventricular failure	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Myocardial ischemia	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Palpitations	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Sinus tachycardia	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Cardiac disorders Supraventricular tachycardia	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Ear and labyrinth disorders Hearing impaired	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Ear and labyrinth disorders Tinnitus	0.32% 1/310 • Number of events 7 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Eye disorders Cataract	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Eye disorders Retinal detachment	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Eye disorders Retinopathy	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 10 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Eye disorders Vision blurred	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Abdominal pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Ascites	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Colonic obstruction	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Constipation	1.6% 5/310 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.9% 6/308 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Diarrhea	19.7% 61/310 • Number of events 148 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	16.9% 52/308 • Number of events 127 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Diarrhea patients with a colostomy	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Jejunal obstruction	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Jejunal ulcer	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Nausea	22.6% 70/310 • Number of events 150 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	25.3% 78/308 • Number of events 209 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Rectal pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Salivary gland disorder	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Small intestinal obstruction	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Stomach pain	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Tooth disorder	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Gastrointestinal disorders Vomiting	12.9% 40/310 • Number of events 59 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	13.3% 41/308 • Number of events 67 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Chest pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Chills	11.9% 37/310 • Number of events 64 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	8.1% 25/308 • Number of events 55 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Disease progression	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Fatigue	61.6% 191/310 • Number of events 1076 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	62.7% 193/308 • Number of events 1232 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Fever	13.9% 43/310 • Number of events 56 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	9.4% 29/308 • Number of events 42 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Gait abnormal	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
General disorders Pain	1.3% 4/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Immune system disorders Hypersensitivity	2.6% 8/310 • Number of events 12 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.9% 6/308 • Number of events 22 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Bladder infection	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Catheter related infection	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Infection	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Infection without neutropenia	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Infective myositis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Otitis externa	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Infections and infestations Pneumonia	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum magnesium decreased	7.4% 23/310 • Number of events 34 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	9.1% 28/308 • Number of events 100 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum magnesium increased	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum phosphate decreased	12.3% 38/310 • Number of events 101 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	12.3% 38/308 • Number of events 79 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum potassium decreased	14.2% 44/310 • Number of events 108 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	11.7% 36/308 • Number of events 89 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum potassium increased	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum sodium decreased	1.9% 6/310 • Number of events 7 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.6% 5/308 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Metabolism and nutrition disorders Serum sodium increased	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Arthralgia	2.3% 7/310 • Number of events 12 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.9% 6/308 • Number of events 8 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Back pain	4.5% 14/310 • Number of events 32 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	2.6% 8/308 • Number of events 11 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Bone pain	6.5% 20/310 • Number of events 32 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	6.8% 21/308 • Number of events 30 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Joint disorder	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Muscle weakness	1.3% 4/310 • Number of events 8 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 11 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Myalgia	53.5% 166/310 • Number of events 849 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	45.5% 140/308 • Number of events 680 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Neck pain	0.32% 1/310 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Osteonecrosis	2.6% 8/310 • Number of events 11 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.9% 6/308 • Number of events 7 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Musculoskeletal and connective tissue disorders Pain in extremity	0.97% 3/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	0.97% 3/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Depressed level of consciousness	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Dizziness	0.32% 1/310 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Dysgeusia	0.65% 2/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Headache	1.3% 4/310 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Mini mental status examination abnormal	0.32% 1/310 • Number of events 17 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Neuralgia	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Neurological disorder NOS	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Peripheral motor neuropathy	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Seizure	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Syncope	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Nervous system disorders Syncope vasovagal	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Psychiatric disorders Agitation	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Psychiatric disorders Anxiety	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Psychiatric disorders Depression	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Psychiatric disorders Insomnia	1.6% 5/310 • Number of events 13 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Cystitis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Hemorrhage urinary tract	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Kidney pain	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Kidney perforation	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Urinary frequency	0.65% 2/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.6% 5/308 • Number of events 12 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Urinary retention	0.97% 3/310 • Number of events 6 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.3% 4/308 • Number of events 7 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Renal and urinary disorders Urogenital disorder	0.32% 1/310 • Number of events 4 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.65% 2/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Reproductive system and breast disorders Erectile dysfunction	3.2% 10/310 • Number of events 42 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.6% 5/308 • Number of events 46 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Reproductive system and breast disorders Gynecomastia	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Reproductive system and breast disorders Pelvic pain	0.32% 1/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Reproductive system and breast disorders Prostatic obstruction	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Reproductive system and breast disorders Testicular pain	0.65% 2/310 • Number of events 2 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Cough	0.97% 3/310 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.6% 5/308 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.3% 7/310 • Number of events 7 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	2.3% 7/308 • Number of events 20 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 12 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Pharyngeal stenosis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Skin and subcutaneous tissue disorders Alopecia	0.32% 1/310 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/310 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.32% 1/308 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Skin and subcutaneous tissue disorders Pruritus	7.1% 22/310 • Number of events 70 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	8.1% 25/308 • Number of events 79 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Skin and subcutaneous tissue disorders Rash desquamating	11.6% 36/310 • Number of events 74 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	15.3% 47/308 • Number of events 120 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Skin and subcutaneous tissue disorders Skin disorder	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Vascular disorders Hemorrhage	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Vascular disorders Hot flashes	1.3% 4/310 • Number of events 11 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 5 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Vascular disorders Hypertension	1.3% 4/310 • Number of events 8 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	1.6% 5/308 • Number of events 11 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Vascular disorders Hypotension	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.00% 0/308 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.
Vascular disorders Thrombosis	0.32% 1/310 • Number of events 1 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.	0.97% 3/308 • Number of events 3 All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.

Additional Information

Matthew Smith, MD, PhD

Massachusetts General Hospital

Email: smith.matthew@mgh.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee Must obtain prior Sponsor approval.
• Publication restrictions are in place

Restriction type: OTHER