Trial Outcomes & Findings for Memantine in Preventing Side Effects in Patients Undergoing Whole-Brain Radiation Therapy for Brain Metastases From Solid Tumors (NCT NCT00566852)

NCT ID: NCT00566852

Last Updated: 2017-08-21

Results Overview

The HVLT-R consists of 3 parts. Free call has a range of 0 to 36, delayed recall has a range from 0 to 12, and delayed recognition has a range of -12 to 12. Higher scores indicating better function in all 3 parts. Standardized scores are used by calculating an average standardized z score for each part of the HVLT-R. Change is calculated by subtracting baseline value from 24-week value. Imputation methods were used to determine values for all alive patients missing the 24 week assessment. This tool is being used to measure cognitive function, specifically memory.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 554 participants
• Primary outcome timeframe: Baseline and 24 weeks from the start of drug treatment
• Results posted on: 2017-08-21

Participant Flow

Participant milestones

Measure	WBRT+Memantine Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo Whole brain radiation therapy (WBRT) and placebo
Overall Study STARTED	278	276
Overall Study COMPLETED	71	78
Overall Study NOT COMPLETED	207	198

Reasons for withdrawal

Measure	WBRT+Memantine Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo Whole brain radiation therapy (WBRT) and placebo
Overall Study Protocol Violation	22	24
Overall Study Death	95	78
Overall Study Withdrawal by Subject	30	25
Overall Study Patient refusal	37	37
Overall Study Not tested due to disability	6	12
Overall Study Missing reason not specified	1	2
Overall Study Missing reason not reported	16	20

Baseline Characteristics

Memantine in Preventing Side Effects in Patients Undergoing Whole-Brain Radiation Therapy for Brain Metastases From Solid Tumors

Baseline characteristics by cohort

Measure	WBRT+Memantine n=256 Participants Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo n=252 Participants Whole brain radiation therapy (WBRT) and placebo	Total n=508 Participants Total of all reporting groups
Age, Continuous	60 years n=5 Participants	59 years n=7 Participants	59 years n=5 Participants
Sex: Female, Male Female	141 Participants n=5 Participants	145 Participants n=7 Participants	286 Participants n=5 Participants
Sex: Female, Male Male	115 Participants n=5 Participants	107 Participants n=7 Participants	222 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 weeks from the start of drug treatment

Population: All eligible patients with Hopkins Verbal Learning Test-Revised for delayed recall (HVLT-R delayed recall) at baseline and 24 weeks.

The HVLT-R consists of 3 parts. Free call has a range of 0 to 36, delayed recall has a range from 0 to 12, and delayed recognition has a range of -12 to 12. Higher scores indicating better function in all 3 parts. Standardized scores are used by calculating an average standardized z score for each part of the HVLT-R. Change is calculated by subtracting baseline value from 24-week value. Imputation methods were used to determine values for all alive patients missing the 24 week assessment. This tool is being used to measure cognitive function, specifically memory.

Outcome measures

Measure	WBRT+Memantine n=71 Participants Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo n=78 Participants Whole brain radiation therapy (WBRT) and placebo
Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall) at 24 Weeks	0 units on a scale Interval -1.67 to 0.59	-0.9 units on a scale Interval -2.22 to 0.55

SECONDARY outcome

Timeframe: Baseline, 8, 16, and 52 weeks from the start of drug treatment

Population: Eligible patients with baseline and respective post-baseline measurements

The HVLT-R consists of 3 parts. Free call has a range of 0 to 36, delayed recall has a range from 0 to 12, and delayed recognition has a range of -12 to 12. Higher scores indicating better function in all 3 parts. Standardized scores are used by calculating an average standardized z score for each part of the HVLT-R. Change is calculated by subtracting baseline value from the respective later time point value. Imputation methods were used to determine values for all alive patients missing the post-baseline assessments. This tool is being used to measure cognitive function, specifically memory.

Outcome measures

Measure	WBRT+Memantine n=128 Participants Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo n=128 Participants Whole brain radiation therapy (WBRT) and placebo
Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall) at 8, 16, and 52 Weeks 8-weeks	-0.36 units on a scale Interval -1.77 to 0.56	-0.72 units on a scale Interval -1.76 to 0.0
Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall) at 8, 16, and 52 Weeks 16-weeks	0 units on a scale Interval -0.91 to 0.91	0 units on a scale Interval -0.91 to 0.815
Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall) at 8, 16, and 52 Weeks 52-weeks	0 units on a scale Interval -2.0 to 0.71	0 units on a scale Interval -1.82 to 0.72

SECONDARY outcome

Timeframe: Baseline to 12 months from the start of drug treatment

Population: All randomized eligible patients with neurocognitive scores from baseline to 12 months from start of drug treatment.

Neurocognitive failure is defined as the first cognitive failure on any of the neurocognitive tests: the HVLT-R for immediate recall, delayed recognition, and delayed recall; the Controlled Oral Word Association Test (COWAT); the Trail-Making Test (TMT) Parts A and B. Cognitive failure for each test is defined as a post-treatment score that meets one of the following criteria: follow-up score is at least 2 standard deviations worse than the patient's personal baseline score or the patient's raw score change is greater than the reliable change index. The cumulative incidence approach was used to estimate the median time to neurocognitive failure to account for the competing risks of disease progression and death.

Outcome measures

Measure	WBRT+Memantine n=256 Participants Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo n=252 Participants Whole brain radiation therapy (WBRT) and placebo
Median Time to Neurocognitive Failure	2.6 years Interval 2.4 to 3.7	2.3 years Interval 2.1 to 2.6

SECONDARY outcome

Timeframe: Baseline and 24 weeks from start of treatment

Population: Eligible patients with FACT-Br score at baseline and 24 weeks.

The FACT-Br is a 50-question self-report questionnaire contains the following domains (scales): Physical well-being (7 questions), social/family well-being (7 questions), emotional well-being (6 questions), functional well-being (7 questions) and brain cancer subscale which contains concerns relevant to patients with brain tumors (23 questions). Each question has a value 0-4. For some questions a higher indicates better outcome and others are the opposite. The former are summed as is, the latter are reversed in value before adding, such that each domain ranges from 0 to 4 times the number of questions in the domain, with 0 indicating worst and the highest possible value indicating best outcome. The FACT-Br total is obtained by adding all domains together if the overall question response rate is greater than 80%. Total scores on the FACT-Br range from 0 to 184 with lower scores indicating declining quality of life. Change is calculated as baseline score subtracted from 24-week score.

Outcome measures

Measure	WBRT+Memantine n=71 Participants Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo n=66 Participants Whole brain radiation therapy (WBRT) and placebo
Change in Functional Assessment of Cancer Therapy With Brain Subscale (FACT-Br) at 24 Weeks	0 units on a scale Interval -14.0 to 16.0	1 units on a scale Interval -10.0 to 12.0

SECONDARY outcome

Timeframe: From randomization to date of progression, death or last follow-up. Analysis occurs at the same time as the primary outcome. Patients are followed until death and all follow-up collected at time of analysis is used.

Population: All eligible patients

Disease progression is defined as the first of the following events: an increase of at least 50% for lesions less than or equal to 1cm, an increase of least 25% for lesions greater than 1cm, appearance of any new brain metastases. Failure for progression-free survival is disease progression or death. Median progression-free survival was estimated using the Kaplan-Meier method.

Outcome measures

Measure	WBRT+Memantine n=256 Participants Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo n=252 Participants Whole brain radiation therapy (WBRT) and placebo
Median Progression-free Survival Time	4.7 months Interval 3.7 to 5.6	5.5 months Interval 4.8 to 6.2

SECONDARY outcome

Timeframe: From randomization to date of death or last follow-up. Analysis occurs at the same time as the primary outcome. Patients are followed until death and all follow-up collected at time of analysis is used.

Population: All eligible patients

Failure for overall survival is death from any cause. Median survival was estimated using the Kaplan-Meier method.

Outcome measures

Measure	WBRT+Memantine n=256 Participants Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo n=252 Participants Whole brain radiation therapy (WBRT) and placebo
Overall Survival	6.7 months Interval 5.3 to 10.2	7.8 months Interval 6.4 to 9.6

Adverse Events

WBRT+Memantine

Serious events: 80 serious events

Other events: 160 other events

Deaths: 0 deaths

WBRT+Placebo

Serious events: 67 serious events

Other events: 166 other events

Deaths: 0 deaths

Serious adverse events

Measure	WBRT+Memantine n=251 participants at risk Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo n=246 participants at risk Whole brain radiation therapy (WBRT) and placebo
Blood and lymphatic system disorders Blood disorder	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Blood and lymphatic system disorders Febrile neutropenia	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Blood and lymphatic system disorders Hemoglobin decreased	1.6% 4/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	2.8% 7/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Arrhythmia supraventricular	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Atrial fibrillation	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Atrial flutter	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Cardiac disorder	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Cardiac pain	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Left ventricular failure	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Myocardial ischemia	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Pericardial effusion	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Cardiac disorders Sinus tachycardia	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Ear and labyrinth disorders Ear pain	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Ear and labyrinth disorders External ear inflammation	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Ear and labyrinth disorders Hearing loss	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Eye disorders Eye disorder	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Eye disorders Vision blurred	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Abdominal pain	2.0% 5/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.6% 4/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Colonic hemorrhage	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Constipation	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Diarrhea	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Dysphagia	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Ileal perforation	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Ileus	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Mucositis oral	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Nausea	3.6% 9/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	2.4% 6/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Pancreatitis	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Vomiting	4.0% 10/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.7% 9/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Chest pain	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Death	4.0% 10/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	4.9% 12/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Disease progression	4.8% 12/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	4.1% 10/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Edema limbs	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Fatigue	3.6% 9/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.7% 9/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Fever	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders General symptom	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Pain [NOS]	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Pain [other]	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Sudden death	1.2% 3/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Colitis, infectious (e.g., Clostridium difficile)	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Eye infection [with normal or Grade 1-2 ANC]	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Infection [neck, with normal or Grade 1-2 ANC]	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Infection [other]	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Infectious colitis [with unknown ANC]	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Infectious meningitis [with unknown ANC]	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Peritoneal infection [with unknown ANC]	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Pleural infection [with normal or Grade 1-2 ANC]	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Pneumonia [with Grade 3-4 ANC]	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Pneumonia [with normal or Grade 1-2 ANC]	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.2% 3/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Pneumonia [with unknown ANC]	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.2% 3/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Urinary tract infection [with normal or Grade 1-2 ANC]	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Infections and infestations Wound infection [with unknown ANC]	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Injury, poisoning and procedural complications Arterial injury - Extremity-upper	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Injury, poisoning and procedural complications Fracture	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Alanine aminotransferase increased	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Alkaline phosphatase increased	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Aspartate aminotransferase increased	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Cardiac troponin I increased	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Creatinine increased	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations INR increased	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Laboratory test abnormal	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Leukopenia	1.2% 3/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Lymphopenia	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Neutrophil count decreased	1.2% 3/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Platelet count decreased	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.2% 3/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Weight loss	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.6% 4/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Acidosis	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Anorexia	1.2% 3/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Dehydration	3.2% 8/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.3% 8/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Hyperglycemia	1.2% 3/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	2.0% 5/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Hypokalemia	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Hyponatremia	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.6% 4/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Musculoskeletal and connective tissue disorders Back pain	1.2% 3/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.2% 3/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Musculoskeletal and connective tissue disorders Bone pain	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Musculoskeletal and connective tissue disorders Joint pain	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness	2.4% 6/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.6% 4/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Musculoskeletal and connective tissue disorders Neck pain	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Ataxia	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Cognitive disturbance	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.6% 4/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Depressed level of consciousness	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.6% 4/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Dizziness	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Encephalopathy	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Headache	2.4% 6/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Ischemia cerebrovascular	1.2% 3/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Memory impairment	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Mental status changes	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Neurological disorder NOS	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Nystagmus	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Peripheral motor neuropathy	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.6% 4/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Seizure	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Speech disorder	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Syncope	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Psychiatric disorders Agitation	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Psychiatric disorders Confusion	1.6% 4/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	2.0% 5/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Psychiatric disorders Depression	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Psychiatric disorders Insomnia	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Psychiatric disorders Personality change	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Psychiatric disorders Psychosis	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Renal and urinary disorders Bladder hemorrhage	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Renal and urinary disorders Renal failure	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Renal and urinary disorders Urinary incontinence	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Reproductive system and breast disorders Pelvic pain	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Cough	1.2% 3/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.4% 11/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	2.4% 6/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Hemorrhage nasal	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.6% 4/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.81% 2/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.6% 4/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	1.2% 3/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	1.2% 3/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Skin and subcutaneous tissue disorders Sweating	0.00% 0/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Vascular disorders Hypertension	0.40% 1/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.00% 0/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Vascular disorders Hypotension	0.80% 2/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	0.41% 1/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Vascular disorders Thrombosis	2.8% 7/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.7% 9/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.

Other adverse events

Measure	WBRT+Memantine n=251 participants at risk Whole brain radiation therapy (WBRT) and memantine	WBRT+Placebo n=246 participants at risk Whole brain radiation therapy (WBRT) and placebo
Blood and lymphatic system disorders Hemoglobin decreased	11.2% 28/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	12.2% 30/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Ear and labyrinth disorders Hearing loss	6.0% 15/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	8.1% 20/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Constipation	13.5% 34/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	10.2% 25/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Diarrhea	2.4% 6/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.1% 15/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Nausea	22.3% 56/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	27.2% 67/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Gastrointestinal disorders Vomiting	6.0% 15/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	13.8% 34/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Edema limbs	2.8% 7/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.3% 13/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
General disorders Fatigue	46.6% 117/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	43.5% 107/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Injury, poisoning and procedural complications Dermatitis radiation	3.6% 9/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	8.1% 20/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Injury, poisoning and procedural complications Radiation recall reaction (dermatologic)	4.8% 12/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	8.1% 20/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Alanine aminotransferase increased	4.4% 11/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.9% 17/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Alkaline phosphatase increased	4.4% 11/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.7% 14/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Aspartate aminotransferase increased	2.4% 6/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.1% 15/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Laboratory test abnormal	4.8% 12/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.7% 14/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Leukopenia	5.6% 14/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.3% 13/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Lymphopenia	8.0% 20/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	3.7% 9/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Platelet count decreased	7.2% 18/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.1% 15/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Investigations Weight loss	8.8% 22/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	11.0% 27/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Anorexia	13.9% 35/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	14.2% 35/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Hyperglycemia	11.2% 28/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	8.5% 21/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	7.2% 18/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.1% 15/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Metabolism and nutrition disorders Hyponatremia	7.6% 19/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.5% 16/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Musculoskeletal and connective tissue disorders Back pain	4.8% 12/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	8.5% 21/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness	2.8% 7/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.7% 14/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Ataxia	3.2% 8/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.7% 14/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Dizziness	8.4% 21/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	12.6% 31/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Headache	20.7% 52/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	19.5% 48/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Memory impairment	6.0% 15/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	9.3% 23/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Peripheral motor neuropathy	5.6% 14/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.3% 13/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Peripheral sensory neuropathy	9.6% 24/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.1% 15/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Seizure	2.4% 6/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.3% 13/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Nervous system disorders Taste alteration	3.2% 8/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	5.7% 14/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Psychiatric disorders Depression	5.2% 13/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	6.1% 15/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Psychiatric disorders Insomnia	8.4% 21/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	8.1% 20/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Cough	8.4% 21/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	8.5% 21/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	12.7% 32/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	10.2% 25/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Skin and subcutaneous tissue disorders Alopecia	27.1% 68/251 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.	26.4% 65/246 Adverse events are reported for all eligible randomized patients with adverse event data. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

Email: seiferheldw@nrgoncology.org

Results disclosure agreements

• Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
• Publication restrictions are in place

Restriction type: OTHER