Trial Outcomes & Findings for Memantine for Prevention of Cognitive Decline in Patients With Breast Cancer (NCT NCT04033419)

Last Updated: 2023-04-20

Results Overview

The Delayed Matching to Sample Test (DMS) is a computerized cognitive assessment of visual working memory. The DMS will be administered using Cambridge Neuropsychological Test Automated Battery (CANTAB) eclipse software (Cambridge Cognition, Cambridge, UK). The participant is shown an image with four patterns and asked to match patterns simultaneously or after delay. The investigators will use the percent correct (0 to 100, higher is better) at the 12-second delay on the DMS test for the primary analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Results posted on

2023-04-20

Participant Flow

Participants were recruited from 09/25/2019 through 08/13/2021 at six cancer centers in North Carolina.

A total of fifty-six participants consented to the study, but one of them was deemed to be ineligible therefore 55 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	Memantine Memantine: - Week 1: 5 mg dose once daily * Week 2: 5 mg dose twice daily * Week 3: 5 mg each morning/10 mg each evening * Week 4 through end of Chemotherapy: 10 mg dose twice daily * Total duration: 12 - 26 weeks (depending on chemotherapy regimen)
Overall Study STARTED	51
Overall Study COMPLETED	45
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Memantine for Prevention of Cognitive Decline in Patients With Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Memantine n=55 Participants Memantine: - Week 1: 5 mg dose once daily * Week 2: 5 mg dose twice daily * Week 3: 5 mg each morning/10 mg each evening * Week 4 through end of Chemotherapy: 10 mg dose twice daily * Total duration: 12 - 26 weeks (depending on chemotherapy regimen)
Age, Continuous	56.1 years n=93 Participants
Sex: Female, Male Female	54 Participants n=93 Participants
Sex: Female, Male Male	1 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	53 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	10 Participants n=93 Participants
Race (NIH/OMB) White	42 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=93 Participants
Region of Enrollment United States	55 participants n=93 Participants

PRIMARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: Forty-five subjects had at least one dose of memantine and completed both pre- and post-assessments and, thus, were evaluable for cognitive change.

Outcome measures

Outcome measures
Measure	Memantine n=45 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Visual Working Memory - Delayed Matching to Sample Test Declined	16 Participants	—	—
Change in Visual Working Memory - Delayed Matching to Sample Test Improved	16 Participants	—	—
Change in Visual Working Memory - Delayed Matching to Sample Test No Change	13 Participants	—	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: Forty-five subjects had at least one dose of memantine and completed both pre- and post-assessments and, thus, were evaluable for cognitive change.

The Hopkins Verbal Learning Test-Revised (HVLT-R) is an objective measure of verbal learning and memory. The examiner reads a list of 12 nouns to the participant, who repeats as many words as remembered. Approximately 20-25 minutes later, participants are asked to recall as many words as possible. Then, the examiner reads a list of 24 words, including the 12 words from the original list, and the participant is asked to determine which words were and were not on the original list. These tasks result in three subscales: total recall (range: 0-36; higher is better), delayed recall (range: 0-12; higher is better), and the Recognition Discrimination Index (range: 0-12; higher is better).

Outcome measures

Outcome measures
Measure	Memantine n=45 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Verbal Memory - Hopkins Verbal Learning Test-Revised Improved	22 Participants	—	—
Change in Verbal Memory - Hopkins Verbal Learning Test-Revised No Change	16 Participants	—	—
Change in Verbal Memory - Hopkins Verbal Learning Test-Revised Declined	7 Participants	—	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: The participants received memantine and completed both pre- and post-assessments. Due COVID-19 pandemic, only 3 participants received memantine and completed both pre- and post-assessments. Their data was entered.

The Trail Making Test (TMT) is an objective measure of processing speed (part A) and executive function (part B). In part A, the participant is given a diagram of 25 circles, labeled 1 - 25, and asked to connect the circles in ascending order. In part B, the diagram of 25 circles includes some with numbers (1-13) and some with letters (A-L), and the participant is asked to connect the circles alternating between numbers and letters. Performance is measured in the number of seconds required to complete each task (lower is better).

Outcome measures

Outcome measures
Measure	Memantine n=3 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) n=3 Participants Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Processing Speed and Executive Function - Trail Making Test Baseline	27.58 time seconds Standard Deviation 2.325	79.42 time seconds Standard Deviation 25.54	—
Change in Processing Speed and Executive Function - Trail Making Test Post-chemotherapy	32.65 time seconds Standard Deviation 11.32	87.53 time seconds Standard Deviation 11.32	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: Forty-five subjects had at least one dose of memantine and completed both pre- and post-assessments. There are data available for 31 subjects. and, thus, were evaluable for cognitive change.

The Rapid Visual Processing test (RVP) is a computerized cognitive assessment of processing speed and sustained attention. The RVP will be administered using Cambridge Neuropsychological Test Automated Battery (CANTAB) eclipse software (Cambridge Cognition, Cambridge, UK). The participant is shown a series of pseudo-random digits from 2 to 9 and asked to recognize target digit sequences by pressing a button on the screen as quickly as possible. The investigators will measure total correct responses (higher is better). This test was added at the start of the COVID-19 pandemic as a substitute for the Trail Making Test.

Outcome measures

Outcome measures
Measure	Memantine n=31 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Processing Speed - Rapid Visual Processing (RVP) Improved	10 Participants	—	—
Change in Processing Speed - Rapid Visual Processing (RVP) No Change	17 Participants	—	—
Change in Processing Speed - Rapid Visual Processing (RVP) Declined	4 Participants	—	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: This test was added at the start of the COVID-19 pandemic as a substitute for the Trail Making Test. Accordingly, 31 subjects had at least one dose of memantine and completed both pre- and post-assessments and, thus, were evaluable for cognitive change.

The One Touch Stockings (OTS) of Cambridge is a computerized cognitive assessment of executive function. The OTS will be administered using Cambridge Neuropsychological Test Automated Battery (CANTAB) eclipse software (Cambridge Cognition, Cambridge, UK). The participant is shown two displays with three colored balls presented as stacks suspended from a beam and a row of numbered boxes along the bottom of the screen. The participant is asked to work out in their head how many moves are required to match the two displays. The investigators will measure mean number of choices to the correct response (lower is better).

Outcome measures

Outcome measures
Measure	Memantine n=31 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Executive Function - One Touch Stockings (OTS) of Cambridge No Change	16 Participants	—	—
Change in Executive Function - One Touch Stockings (OTS) of Cambridge Declined	6 Participants	—	—
Change in Executive Function - One Touch Stockings (OTS) of Cambridge Improved	9 Participants	—	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: Forty-five subjects had at least one dose of memantine and completed both pre- and post-assessments and, thus, were evaluable for cognitive change.

The Digit Span is an objective measure of attention and working memory. The participant is asked to recite sequences of numbers in forward, backwards, and sequential order. The score for each sequence type is the number of correct responses (higher is better).

Outcome measures

Outcome measures
Measure	Memantine n=45 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Attention and Working Memory - Digit Span Improved	7 Participants	—	—
Change in Attention and Working Memory - Digit Span No Change	31 Participants	—	—
Change in Attention and Working Memory - Digit Span Declined	7 Participants	—	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: Forty-five subjects had at least one dose of memantine and completed both pre- and post-assessments and, thus, were evaluable for cognitive change.

The Controlled Oral Word Association Test (COWA) is an objective measure of verbal fluency. The participant is asked to name as many words as possible, excluding proper nouns, in one minute. This is repeated for a total for three different letters. The score is the total number of different words produced between all three letters (higher is better).

Outcome measures

Outcome measures
Measure	Memantine n=45 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Verbal Fluency - Controlled Oral Word Association Test Improved	18 Participants	—	—
Change in Verbal Fluency - Controlled Oral Word Association Test No Change	18 Participants	—	—
Change in Verbal Fluency - Controlled Oral Word Association Test Declined	9 Participants	—	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: Forty-five subjects had at least one dose of memantine and completed both pre- and post-assessments and, thus, were evaluable for cognitive change.

The Animal Naming Test (ANT) is an objective measure of semantic fluency. The participant is asked to name as many animals as possible in one minute. The score is the number of unique animals stated (higher is better).

Outcome measures

Outcome measures
Measure	Memantine n=45 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Semantic Fluency - Animal Naming Test Improved	10 Participants	—	—
Change in Semantic Fluency - Animal Naming Test No Change	16 Participants	—	—
Change in Semantic Fluency - Animal Naming Test Declined	19 Participants	—	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: Forty-four subjects had at least one dose of memantine and completed both pre- and post-assessments and, thus, were evaluable for cognitive change.

The National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) contains a cognitive function bank. The PROMIS Cognitive Function 8a short form will be used. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of cognitive complaints.

Outcome measures

Outcome measures
Measure	Memantine n=33 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) n=10 Participants Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline n=1 Participants Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Self-reported Cognitive Function - PROMIS Cognitive Function Normal Function at Follow-Up	18 Participants	2 Participants	1 Participants
Change in Self-reported Cognitive Function - PROMIS Cognitive Function Decline to Mild at Follow-Up Cognitive Difficulties	14 Participants	8 Participants	0 Participants
Change in Self-reported Cognitive Function - PROMIS Cognitive Function Decline to Moderate at Follow-Up Cognitive Difficulties	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: Fifty-one subjects provided data regarding depression symptoms at baseline and forty-four provided data at follow-up. All available data were included to evaluate changes in depressive symptoms.

The National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) contains a depression bank. The PROMIS Depression 8a short form will be used. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of depression. We evaluated the proportion of patients with at least moderately severe symptoms (T-score ≥ 65) at baseline and follow-up.

Outcome measures

Outcome measures
Measure	Memantine n=51 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) n=44 Participants Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Depressive Symptoms - PROMIS Depression PROMIS Depression Score <65	50 Participants	43 Participants	—
Change in Depressive Symptoms - PROMIS Depression PROMIS Depression Score Value ≥ 65	1 Participants	1 Participants	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy.

Population: Anxiety was assessed using the PROMIS Emotional Distress-Anxiety measure, in 51 subjects at baseline (all enrolled who had at least one dose of memantine) and in 45 subjects at the post-assessment (all who completed this measure at the post-assessment timepoint and had at least one dose of memantine)

The National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) contains an anxiety bank. The PROMIS Emotional Distress-Anxiety - Short Form 6a will be used. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of anxiety. We evaluated the proportion of patients with at least moderately severe symptoms (T-score ≥ 65) at baseline and follow-up.

Outcome measures

Outcome measures
Measure	Memantine n=51 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) n=45 Participants Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Anxiety Symptoms - PROMIS Emotional Distress-Anxiety PROMIS Anxiety Score <65	48 Participants	40 Participants	—
Change in Anxiety Symptoms - PROMIS Emotional Distress-Anxiety PROMIS Anxiety Score ≥ 65	3 Participants	5 Participants	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: Karnofsky Performance Status of subjects was assessed both at baseline and 4 weeks after the completion of chemotherapy.

The number of subjects with Karnofsky Performance Status equal to or more than 80, at baseline and 4 weeks after chemotherapy were compared. The Patient-reported Karnofsky Performance Status (KPS) provides a self-characterization of functional status, ranging from severe/requiring continuous nursing care to normal/no complaints/no symptoms of the disease. Scores range from 30 to 100. Higher scores indicate better function.

Outcome measures

Outcome measures
Measure	Memantine n=42 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Karnofsky Performance Status Baseline Karnofsky Performance Status · => 80	37 Participants	—	—
Change in Karnofsky Performance Status Baseline Karnofsky Performance Status · <80	5 Participants	—	—
Change in Karnofsky Performance Status Post-treatment Karnofsky Performance Status · => 80	39 Participants	—	—
Change in Karnofsky Performance Status Post-treatment Karnofsky Performance Status · <80	3 Participants	—	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: Subjects FACT-G scores were assessed both at baseline and 4 weeks after the completion of chemotherapy.

The Functional Assessment of Cancer Therapy-General (FACT-G) is a 27-item patient-administered assessment of general quality-of-life measures in cancer patients. It has been validated in the literature and permits the measurement of a number of symptoms including nausea, pain, and insomnia. Responses to each item are on a 5-point Likert scale. The FACT-G total score (range: 0-108; higher is better) will be assessed.

Outcome measures

Outcome measures
Measure	Memantine n=43 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Change in Quality of Life - Functional Assessment of Cancer Therapy-General Baseline FACT-G	83.7 score on a scale Standard Deviation 15.1	—	—
Change in Quality of Life - Functional Assessment of Cancer Therapy-General Post-treatment FACT-G	82.6 score on a scale Standard Deviation 13.9	—	—

SECONDARY outcome

Timeframe: Baseline (pre-chemotherapy) over the duration of the accrual period

Population: The number of subjects who were assessed for eligibility enrolled and withdrawn.

Feasibility will be based on recruitment success as measured by the proportion of invited participants who enroll.

Outcome measures

Outcome measures
Measure	Memantine n=412 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Proportion of Invited Participants Who Enroll - Recruitment Assessed for eligibility	412 Participants	—	—
Proportion of Invited Participants Who Enroll - Recruitment Enrolled	55 Participants	—	—
Proportion of Invited Participants Who Enroll - Recruitment Withdrew	4 Participants	—	—
Proportion of Invited Participants Who Enroll - Recruitment Received at least 1 dose	51 Participants	—	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: The subject received at least one dose of memantine.

Feasibility will be based on retention success as measured by the proportion of enrolled participants who are not eligible for analysis of the primary outcome.

Outcome measures

Outcome measures
Measure	Memantine n=51 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Proportion of Enrolled Participants Who do Not Meet the Primary Outcome Measure - Attrition Evaluable	45 Participants	—	—
Proportion of Enrolled Participants Who do Not Meet the Primary Outcome Measure - Attrition Withdrew	3 Participants	—	—
Proportion of Enrolled Participants Who do Not Meet the Primary Outcome Measure - Attrition Lost to follow-up	3 Participants	—	—

SECONDARY outcome

Timeframe: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Population: All subjects enrolled in the study.

Feasibility will be based on adherence success as measured by the proportion of self-reported doses of memantine taken.

Outcome measures

Outcome measures
Measure	Memantine n=55 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Proportion of Scheduled Drug Doses Taken - Adherence never initiated memantine	4 Participants	—	—
Proportion of Scheduled Drug Doses Taken - Adherence >= 90% compliance	39 Participants	—	—
Proportion of Scheduled Drug Doses Taken - Adherence <90% compliance	12 Participants	—	—

SECONDARY outcome

Timeframe: From baseline to 4 weeks after chemotherapy (up to 30 weeks)

Population: All subjects who received at least one dose of memantine were assessed for adverse events. Four of the 55 subjects who enrolled did not receive memantine and were not evaluated for adverse events.

Safety is based on the number of all adverse events (AE) associated with memantine. The following most common side effects of memantine were explicitly solicited: headache, dizziness, confusion, constipation, diarrhea, and fatigue. AE was assessed and graded according to the NCI Common Terminology Criteria. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Outcome measures

Outcome measures
Measure	Memantine n=51 Participants Subjects received memantine and completed the visual working memory - Delayed Matching to Sample Test	The Trail Making Test PART B Time (Secs.) Participants received memantine and completed both pre- and post-assessments.	Initial Severe Decline Baseline Cognitive Function based on PROMIS patient-reported outcome
Number of Adverse Events - Safety fatigue	19 Participants	—	—
Number of Adverse Events - Safety headache	16 Participants	—	—
Number of Adverse Events - Safety constipation	12 Participants	—	—
Number of Adverse Events - Safety diarrhea	12 Participants	—	—
Number of Adverse Events - Safety confusion	4 Participants	—	—
Number of Adverse Events - Safety dizziness	10 Participants	—	—

Adverse Events

All Subjects

Serious events: 0 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	All Subjects n=51 participants at risk Subjects who had at least one dose of memantine.
Blood and lymphatic system disorders Anemia	7.8% 4/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Blood and lymphatic system disorders Eosinophilia	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Blood and lymphatic system disorders Febrile neutropenia	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Blood and lymphatic system disorders Thrombocytopenia	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Cardiac disorders Palpitations	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Ear and labyrinth disorders Tinnitus	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Eye disorders blurred vision	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders abdominal pain	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders constipation	23.5% 12/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders diarrhea	23.5% 12/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders dyspepsia	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders gastritis	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders gastrointestinal pain	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders gastrointestinal reflux	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders hematochezia	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders hemorrhoids	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders Mucositis oral	7.8% 4/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders nausea	13.7% 7/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders vomiting	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Gastrointestinal disorders Chills	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
General disorders Fatigue	37.3% 19/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
General disorders fever	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
General disorders Generalized edema	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
General disorders Non-cardiac chest pain	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Infections and infestations lung infection	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Investigations Alkaline phosphatase increased	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Investigations Aspartate aminotransferase increased	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Investigations Creatinine Increased	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Metabolism and nutrition disorders hypercalcemia	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Metabolism and nutrition disorders Hyperglycemia	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Metabolism and nutrition disorders Hyperkalemia	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Metabolism and nutrition disorders hypoalbuminemia	5.9% 3/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Metabolism and nutrition disorders hypocalcemia	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Metabolism and nutrition disorders hypokalemia	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Musculoskeletal and connective tissue disorders arthralgia	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Musculoskeletal and connective tissue disorders Myalgia	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Musculoskeletal and connective tissue disorders Pain in extremity	9.8% 5/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Nervous system disorders Cognitive disturbance	9.8% 5/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Nervous system disorders confusion	7.8% 4/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Nervous system disorders Depressed level of consciousness	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Nervous system disorders dizziness	19.6% 10/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Nervous system disorders Extrapyramidal disorder	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Nervous system disorders headache	31.4% 16/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Nervous system disorders Memory Impairment	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Nervous system disorders paresthesia	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Nervous system disorders Peripheral sensory neuropathy	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Nervous system disorders Syncope	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Psychiatric disorders insomnia	13.7% 7/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Psychiatric disorders Restlessness	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Renal and urinary disorders Dysuria	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Respiratory, thoracic and mediastinal disorders Cough	9.8% 5/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.9% 3/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Respiratory, thoracic and mediastinal disorders pneumonitis	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Skin and subcutaneous tissue disorders alopecia	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Skin and subcutaneous tissue disorders Dry skin	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Skin and subcutaneous tissue disorders Erythroderma	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Skin and subcutaneous tissue disorders Pruritus	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Skin and subcutaneous tissue disorders rash (pistular)	13.7% 7/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Skin and subcutaneous tissue disorders Rash Maculo-papular	3.9% 2/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Skin and subcutaneous tissue disorders Flushing	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.
Vascular disorders hypotension	2.0% 1/51 • Adverse events (AE) were collected from day one of the study drug administration to 4 weeks after completion of treatment (up to 30 weeks). AE were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. All patient-reported symptoms were recorded and examined for their association with memantine. Adverse Events associated with memantine. The most common adverse events of memantine: headache, dizziness, confusion, constipation, diarrhea, and fatigue were specifically collected.

Additional Information

Zev Nakamura, MD

University of North Carolina at Chapel Hill, Department of Psychiatry

Phone: (984) 974-3829

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place