Trial Outcomes & Findings for Exploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer (NCT NCT00525590)

NCT ID: NCT00525590

Last Updated: 2020-03-16

Results Overview

NF was assessed as the performance of 3 neurocognitive domains:memory(MD),executive function(EFD), fine motor coordination(FMCD). For each domain, z-scores were derived from participant's scores in individual neurocognitive tests using an age-adjusted and education-adjusted normative distribution of scores from an unimpaired population.Individual z-scores from related tests were averaged to determine overall z-score.If a z-score average decreased from baseline by greater than or equal to(\>=)3 standard deviations(SD)in tests' normative age-adjusted distribution on 2 consecutive visits or decreased by \>=3 SD on last follow-up visit, participant were considered to have significant deterioration in their NF at time of the first decrease in z-score.Deterioration in NF:demonstrated deterioration for at least two of the three neurocognitive domains based on these changes from screening.Rate of deterioration in NF was measured as estimated percentage of participants using Kaplan-Meier method.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 69 participants
• Primary outcome timeframe: Month 12
• Results posted on: 2020-03-16

Participant Flow

Participants took part in the study at 12 sites in the United States from 12 December 2007 to 01 December 2010.

A total of 82 participants with metastatic brain cancer were screened, of which 69 participants were enrolled and 59 participants were treated.

Participant milestones

Measure	GLIADEL Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 \[milligram\] mg of carmustine). Participants were followed up to 12 months or until the participant experienced local recurrence, withdrew, died, was lost to follow-up, or the study was closed.
Overall Study STARTED	59
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	45

Reasons for withdrawal

Measure	GLIADEL Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 \[milligram\] mg of carmustine). Participants were followed up to 12 months or until the participant experienced local recurrence, withdrew, died, was lost to follow-up, or the study was closed.
Overall Study Adverse Event	3
Overall Study Physician Decision	3
Overall Study Withdrawal by Subject	16
Overall Study Lost to Follow-up	1
Overall Study Death	9
Overall Study Other	13

Baseline Characteristics

Exploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer

Baseline characteristics by cohort

Measure	GLIADEL n=59 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine). Participants were followed up to 12 months or until the participant experienced local recurrence, withdrew, died, was lost to follow-up, or the study was closed.
Age, Continuous	62.0 years STANDARD_DEVIATION 11.60 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	55 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 12

Population: The per protocol 1 (PP1) population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example whole brain radiation therapy \[WBRT\]) before recurrence.

NF was assessed as the performance of 3 neurocognitive domains:memory(MD),executive function(EFD), fine motor coordination(FMCD). For each domain, z-scores were derived from participant's scores in individual neurocognitive tests using an age-adjusted and education-adjusted normative distribution of scores from an unimpaired population.Individual z-scores from related tests were averaged to determine overall z-score.If a z-score average decreased from baseline by greater than or equal to(>=)3 standard deviations(SD)in tests' normative age-adjusted distribution on 2 consecutive visits or decreased by >=3 SD on last follow-up visit, participant were considered to have significant deterioration in their NF at time of the first decrease in z-score.Deterioration in NF:demonstrated deterioration for at least two of the three neurocognitive domains based on these changes from screening.Rate of deterioration in NF was measured as estimated percentage of participants using Kaplan-Meier method.

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Rate of Deterioration in Neurocognitive Functioning (NF) at Month 12	2.8 percentage of participants Interval 0.4 to 18.13

PRIMARY outcome

Timeframe: Month 2

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Number of Participants With Neurocognitive Domains Preserved at Month 2 Domains preserved=3	26 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 2 Domains preserved=2	12 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 2 Domains preserved=1	4 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 2 Domains preserved=0	3 Participants

PRIMARY outcome

Timeframe: Month 4

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Number of Participants With Neurocognitive Domains Preserved at Month 4 Domains preserved=3	24 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 4 Domains preserved=2	9 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 4 Domains preserved=1	2 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 4 Domains preserved=0	1 Participants

PRIMARY outcome

Timeframe: Month 6

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Number of Participants With Neurocognitive Domains Preserved at Month 6 Domains preserved=2	5 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 6 Domains preserved=3	17 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 6 Domains preserved=1	2 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 6 Domains preserved=0	0 Participants

PRIMARY outcome

Timeframe: Month 9

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Number of Participants With Neurocognitive Domains Preserved at Month 9 Domains preserved=3	14 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 9 Domains preserved=2	6 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 9 Domains preserved=1	0 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 9 Domains preserved=0	0 Participants

PRIMARY outcome

Timeframe: Month 12

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

Preservation of NF was defined as a decrease of less than or equal to (<=) 1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Number of Participants With Neurocognitive Domains Preserved at Month 12 Domains preserved=3	9 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 12 Domains preserved=2	5 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 12 Domains preserved=1	0 Participants
Number of Participants With Neurocognitive Domains Preserved at Month 12 Domains preserved=0	0 Participants

SECONDARY outcome

Timeframe: Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Percentage of Participants With Brain Tumor Recurrence (Local Recurrence, Distant Recurrence and Overall Recurrence) Local Recurrence	28.0 percentage of participants
Percentage of Participants With Brain Tumor Recurrence (Local Recurrence, Distant Recurrence and Overall Recurrence) Distant Recurrence	48.0 percentage of participants
Percentage of Participants With Brain Tumor Recurrence (Local Recurrence, Distant Recurrence and Overall Recurrence) Overall Recurrence	62.0 percentage of participants

SECONDARY outcome

Timeframe: Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Time to Recurrence (Local, Distant and Overall) Time to Local Recurrence	NA months Interval 7.5 to Median and upper limit of 95 percent (%) confidence interval were not estimable because less than 50% participants had the event.
Time to Recurrence (Local, Distant and Overall) Time to Distant Recurrence	8.5 months Interval 4.0 to Upper limit of 95% confidence interval was not estimable because majority of the events were censored for the analysis.
Time to Recurrence (Local, Distant and Overall) Time to Overall Recurrence	6.1 months Interval 3.9 to 8.5

SECONDARY outcome

Timeframe: Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)

Population: PP1 population. Since only two participants had residual tumor mass, no correlation analyses were performed for recurrence and residual mass effect.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

The correlation between recurrence (local, distant or overall) & NF was assessed by presenting change in NF domain scores (memory domain [MD], executive function domain [EFD], fine motor coordination domain [FMCD]) after tumor recurrence (Visits X, X+1, X+2, and X+3) compared to before tumor recurrence (Visit X-1). Here 'Visit X' refers to visit at which participants had tumor recurrence, Visit X-1 refers to visit immediately before the recurrence and X+1, X+2, X+3 refers to subsequent first, second & third visit after the recurrence.NF domain z-scores were derived from participant's scores in individual neurocognitive tests using an age-adjusted &education-adjusted normative distribution of scores from an unimpaired population. Individual z-scores from related tests were averaged to determine overall z-score for each of NF domains.

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: MD at Visit (X-1)	-0.9 z-score Standard Deviation 1.21
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: MD Change at Visit (X-1)	-1.1 z-score Standard Deviation 1.11
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: MD Change at Visit (X+1)	0.7 z-score Standard Deviation 0.38
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: MD Change at Visit (X+2)	0.1 z-score Standard Deviation 1.80
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: MD Change at Visit (X+3)	-0.8 z-score Standard Deviation NA Standard deviation could not be calculated since only 1 participant was analyzed.
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: EFD at Visit (X-1)	-0.4 z-score Standard Deviation 1.76
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: EFD Change at Visit (X-1)	-0.5 z-score Standard Deviation 0.62
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: EFD Change at Visit (X+1)	0.2 z-score Standard Deviation 0.89
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: EFD Change at Visit (X+2)	-0.0 z-score Standard Deviation 0.74
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: EFD Change at Visit (X+3)	-1.1 z-score Standard Deviation NA Standard deviation could not be calculated since only 1 participant was analyzed.
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: FMCD at Visit (X-1)	-1.5 z-score Standard Deviation 1.65
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: FMCD Change at Visit (X-1)	0.4 z-score Standard Deviation 0.59
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: FMCD Change at Visit (X+1)	0.5 z-score Standard Deviation 0.53
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: FMCD Change at Visit (X+2)	-0.4 z-score Standard Deviation 0.70
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Local Recurrence: FMCD Change at Visit (X+3)	0.3 z-score Standard Deviation NA Standard deviation could not be calculated since only 1 participant was analyzed.
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: MD at Visit (X-1)	-1.0 z-score Standard Deviation 1.04
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: MD Change at Visit (X-1)	0.2 z-score Standard Deviation 1.35
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: MD Change at Visit (X+1)	-0.2 z-score Standard Deviation 1.02
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: MD Change at Visit (X+2)	-0.2 z-score Standard Deviation 1.77
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: MD Change at Visit (X+3)	-0.7 z-score Standard Deviation 0.07
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: EFD at Visit (X-1)	-0.2 z-score Standard Deviation 1.44
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: EFD Change at Visit (X-1)	-0.2 z-score Standard Deviation 0.82
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: EFD Change at Visit (X+1)	-0.5 z-score Standard Deviation 1.11
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: EFD Change at Visit (X+2)	-0.8 z-score Standard Deviation 1.20
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: EFD Change at Visit (X+3)	-0.8 z-score Standard Deviation 0.39
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: FMCD at Visit (X-1)	-1.2 z-score Standard Deviation 1.32
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: FMCD Change at Visit (X-1)	-0.1 z-score Standard Deviation 0.61
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: FMCD Change at Visit (X+1)	-0.4 z-score Standard Deviation 0.99
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: FMCD Change at Visit (X+2)	-1.1 z-score Standard Deviation 1.03
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Distant Recurrence: FMCD Change at Visit (X+3)	-0.1 z-score Standard Deviation 0.48
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: MD at Visit (X-1)	-0.9 z-score Standard Deviation 1.15
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: MD Change at Visit (X-1)	-0.1 z-score Standard Deviation 1.40
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: MD Change at Visit (X+1)	-0.1 z-score Standard Deviation 0.96
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: MD Change at Visit (X+2)	-0.2 z-score Standard Deviation 1.67
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: MD Change at Visit (X+3)	-0.7 z-score Standard Deviation 0.07
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: EFD at Visit (X-1)	-0.1 z-score Standard Deviation 1.47
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: EFD Change at Visit (X-1)	-0.3 z-score Standard Deviation 0.76
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: EFD Change at Visit (X+1)	-0.5 z-score Standard Deviation 1.01
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: EFD Change at Visit (X+2)	-0.6 z-score Standard Deviation 0.98
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: EFD Change at Visit (X+3)	-0.8 z-score Standard Deviation 0.39
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: FMCD at Visit (X-1)	-1.2 z-score Standard Deviation 1.31
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: FMCD Change at Visit (X-1)	0.0 z-score Standard Deviation 0.69
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: FMCD Change at Visit (X+1)	-0.3 z-score Standard Deviation 0.92
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: FMCD Change at Visit (X+2)	-0.9 z-score Standard Deviation 0.95
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores Overall Recurrence: FMCD Change at Visit (X+3)	-0.1 z-score Standard Deviation 0.48

SECONDARY outcome

Timeframe: Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

Neurologic Death was defined as death due to progression of neurologic disease.

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Percentage of Participants With Neurologic Death	1.9 percentage of participants

SECONDARY outcome

Timeframe: Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

The time to neurocognitive deterioration was defined as the number of days between the date of study treatment and the date of neurocognitive deterioration based on NF assessment. This was assessed using Kaplan Meier method.

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Time to Neurocognitive Deterioration	NA months Time to neurocognitive deterioration was not estimable because majority of the events were censored for the analysis.

SECONDARY outcome

Timeframe: Months 2, 4, 6, 9 and 12

Population: The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

Neurocognitive decline was defined as any decrease in NF scores less than (<) 0 SD from baseline. Here, in category titles EFD represents Executive Function Domain and FMCD represents Fine Motor Coordination Domain.

Outcome measures

Measure	GLIADEL n=54 Participants Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: Memory Domain, decline <0 to -1 SD	27.3 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: Memory Domain, decline <-1 to -2 SD	15.9 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: Memory Domain, decline <-2 to -3 SD	4.5 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: Memory Domain, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: Memory Domain, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: Memory Domain, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: EFD, decline <0 to -1 SD	37.8 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: EFD, decline <-1 to -2 SD	8.1 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: EFD, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: EFD, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: EFD, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: EFD, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: FMCD, decline <0 to -1 SD	23.8 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: FMCD, decline <-1 to -2 SD	7.1 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: FMCD, decline <-2 to -3 SD	2.4 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: FMCD, decline <-3 to -4 SD	2.4 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: FMCD, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 2: FMCD, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: Memory Domain, decline <0 to -1 SD	19.4 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: Memory Domain, decline <-1 to -2 SD	8.3 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: Memory Domain, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: Memory Domain, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: Memory Domain, decline <-4 to -5 SD	2.8 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: Memory Domain, decline <-5 SD	2.8 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: EFD, decline <0 to -1 SD	29.0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: EFD, decline <-1 to -2 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: EFD, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: EFD, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: EFD, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: EFD, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: FMCD, decline <0 to -1 SD	17.1 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: FMCD, decline <-1 to -2 SD	11.4 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: FMCD, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: FMCD, decline <-3 to -4 SD	2.9 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: FMCD, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 4: FMCD, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: Memory Domain, decline <0 to -1 SD	12.5 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: Memory Domain, decline <-1 to -2 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: Memory Domain, decline <-2 to -3 SD	4.2 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: Memory Domain, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: Memory Domain, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: Memory Domain, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: EFD, decline <0 to -1 SD	18.2 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: EFD, decline <-1 to -2 SD	4.5 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: EFD, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: EFD, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: EFD, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: EFD, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: FMCD, decline <0 to -1 SD	12.5 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: FMCD, decline <-1 to -2 SD	20.8 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: FMCD, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: FMCD, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: FMCD, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 6: FMCD, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: Memory Domain, decline <0 to -1 SD	25.0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: Memory Domain, decline <-1 to -2 SD	5.0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: Memory Domain, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: Memory Domain, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: Memory Domain, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: Memory Domain, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: EFD, decline <0 to -1 SD	36.8 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: EFD, decline <-1 to -2 SD	5.3 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: EFD, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: EFD, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: EFD, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: EFD, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: FMCD, decline <0 to -1 SD	20.0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: FMCD, decline <-1 to -2 SD	10.0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: FMCD, decline <-2 to -3 SD	5.0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: FMCD, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: FMCD, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 9: FMCD, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: Memory Domain, decline <0 to -1 SD	14.3 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: Memory Domain, decline <-1 to -2 SD	7.1 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: Memory Domain, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: Memory Domain, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: Memory Domain, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: Memory Domain, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: EFD, decline <0 to -1 SD	33.3 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: EFD, decline <-1 to -2 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: EFD, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: EFD, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: EFD, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: EFD, decline <-5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: FMCD, decline <0 to -1 SD	7.1 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: FMCD, decline <-1 to -2 SD	14.3 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: FMCD, decline <-2 to -3 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: FMCD, decline <-3 to -4 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: FMCD, decline <-4 to -5 SD	0 percentage of participants
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain) Month 12: FMCD, decline <-5 SD	0 percentage of participants

Adverse Events

GLIADEL

Serious events: 40 serious events

Other events: 53 other events

Deaths: 9 deaths

Serious adverse events

Measure	GLIADEL n=59 participants at risk Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine). Participants were followed up to 12 months or until the participant experienced local recurrence, withdrew, died, was lost to follow-up, or the study was closed.
Cardiac disorders Cardiac failure congestive	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Cardiac disorders Cardiopulmonary failure	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Endocrine disorders Adrenal insufficiency	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Lip pain	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Nausea	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Vomiting	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Asthenia	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Drug withdrawal syndrome	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Multi-organ failure	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Pyrexia	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Brain abscess	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Bronchitis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Device related infection	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Pneumonia	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Wound infection	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Haemothorax	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Wound dehiscence	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Investigations Blood creatinine increased	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Metabolism and nutrition disorders Dehydration	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Metabolism and nutrition disorders Failure to thrive	10.2% 6/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Metabolism and nutrition disorders Hyponatraemia	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Musculoskeletal and connective tissue disorders Muscular weakness	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Musculoskeletal and connective tissue disorders Pathological fracture	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Musculoskeletal and connective tissue disorders Soft tissue necrosis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	30.5% 18/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to adrenals	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	11.9% 7/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to small intestine	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm recurrence	8.5% 5/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Convulsion	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Headache	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Intracranial hypotension	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Visual field defect	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Psychiatric disorders Agitation	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Psychiatric disorders Anxiety	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Psychiatric disorders Depression	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Psychiatric disorders Mental status changes	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Renal and urinary disorders Haematuria	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Lung infiltration	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Vascular disorders Deep vein thrombosis	8.5% 5/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.

Other adverse events

Measure	GLIADEL n=59 participants at risk Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine). Participants were followed up to 12 months or until the participant experienced local recurrence, withdrew, died, was lost to follow-up, or the study was closed.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Blood and lymphatic system disorders Anaemia	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Blood and lymphatic system disorders Lymphadenopathy mediastinal	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Blood and lymphatic system disorders Thrombocytopenia	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Cardiac disorders Bradycardia	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Cardiac disorders Tachycardia	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Cardiac disorders Ventricular extrasystoles	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Eye disorders Eye pain	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Eye disorders Lacrimation increased	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Eye disorders Vision blurred	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Eye disorders Vision disturbance	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Abdominal distension	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Abdominal pain	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Constipation	15.3% 9/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Diarrhoea	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Duodenal ulcer	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Dyspepsia	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Dysphagia	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Faecal incontinence	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Gastritis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Hypoaesthesia oral	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Loose tooth	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Nausea	15.3% 9/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Oral soft tissue disorder	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Rectal discharge	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Gastrointestinal disorders Vomiting	6.8% 4/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Asthenia	11.9% 7/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Chest pain	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Drug withdrawal syndrome	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Fatigue	22.0% 13/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Gait disturbance	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Hunger	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Irritability	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Non-cardiac chest pain	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Oedema peripheral	10.2% 6/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
General disorders Pyrexia	8.5% 5/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Immune system disorders Drug hypersensitivity	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Brain abscess	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Bronchitis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Candidiasis	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Device related infection	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Escherichia urinary tract infection	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Herpes virus infection	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Laryngitis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Lobar pneumonia	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Oral candidiasis	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Sinusitis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Upper respiratory tract infection	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Urinary tract infection	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Infections and infestations Wound infection	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Fall	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Incision site complication	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Incision site erythema	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Incision site oedema	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Incision site pain	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Procedural hypertension	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Procedural pain	61.0% 36/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Therapeutic agent toxicity	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Injury, poisoning and procedural complications Thermal burn	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Investigations Blood creatinine increased	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Investigations Blood glucose increased	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Investigations Blood potassium increased	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Investigations Blood pressure increased	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Investigations Breath sounds abnormal	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Investigations Cardiac murmur	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Investigations Weight decreased	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Metabolism and nutrition disorders Decreased appetite	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Metabolism and nutrition disorders Dehydration	6.8% 4/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Metabolism and nutrition disorders Failure to thrive	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Metabolism and nutrition disorders Hyperglycaemia	28.8% 17/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Metabolism and nutrition disorders Hyponatraemia	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Musculoskeletal and connective tissue disorders Arthralgia	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Musculoskeletal and connective tissue disorders Muscular weakness	10.2% 6/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Musculoskeletal and connective tissue disorders Soft tissue necrosis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm recurrence	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Amnesia	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Aphasia	6.8% 4/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Brain stem infarction	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Clumsiness	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Convulsion	10.2% 6/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Coordination abnormal	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Depressed level of consciousness	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Dizziness	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Headache	22.0% 13/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Hemianopia homonymous	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Hemiparesis	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Hypoaesthesia	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Hypokinesia	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders IVth nerve paralysis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Intracranial hypotension	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Lethargy	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Paralysis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Peroneal nerve palsy	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Pneumocephalus	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Nervous system disorders Subdural effusion	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Psychiatric disorders Agitation	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Psychiatric disorders Anxiety	6.8% 4/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Psychiatric disorders Confusional state	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Psychiatric disorders Depression	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Psychiatric disorders Insomnia	5.1% 3/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Psychiatric disorders Mental status changes	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Cough	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.2% 6/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Lung infiltration	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Productive cough	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Respiratory, thoracic and mediastinal disorders Wheezing	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Skin and subcutaneous tissue disorders Drug eruption	6.8% 4/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Skin and subcutaneous tissue disorders Ecchymosis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Skin and subcutaneous tissue disorders Erythema	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Skin and subcutaneous tissue disorders Hypoaesthesia facial	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Skin and subcutaneous tissue disorders Periorbital oedema	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Skin and subcutaneous tissue disorders Petechiae	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Skin and subcutaneous tissue disorders Pruritus	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Skin and subcutaneous tissue disorders Rash	3.4% 2/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Skin and subcutaneous tissue disorders Rash pruritic	1.7% 1/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Vascular disorders Deep vein thrombosis	10.2% 6/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.
Vascular disorders Hypertension	6.8% 4/59 • Screening up to 12 months The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.

Additional Information

Eisai Medical Services

Eisai, Inc.

Phone: 1-888-422-4743

Email: esi_medinfo@eisai.com

Results disclosure agreements

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